Entrenamiento cognitivo para pacientes con demencia leve a moderada
Resumen
Antecedentes
La deficiencia cognitiva, una característica definitoria de la demencia, desempeña una función importante en la independencia funcional comprometida que caracteriza a la afección. El entrenamiento cognitivo (EC) es un enfoque que utiliza la práctica guiada en tareas estructuradas, con el objetivo directo de mejorar o mantener las capacidades cognitivas.
Objetivos
• Evaluar los efectos del EC sobre los resultados cognitivos y no cognitivos en los pacientes con demencia leve a moderada y sus cuidadores.
• Comparar los efectos del EC con los de otras intervenciones no farmacológicas, incluida la estimulación o la rehabilitación cognitiva, para los pacientes con demencia leve a moderada y sus cuidadores.
• Identificar y explorar los factores relacionados con la intervención y el diseño de los ensayos que se pueden asociar con la eficacia del EC para los pacientes con demencia leve a moderada y sus cuidadores.
Métodos de búsqueda
Se hicieron búsquedas en ALOIS, (registro especializado del Grupo Cochrane de Demencia y Trastornos Cognitivos (Cochrane Dementia and Cognitive Improvement Group)) el 5 julio 2018. ALOIS contiene los registros de los ensayos clínicos identificados en las búsquedas mensuales de varias bases de datos principales de atención sanitaria, numerosos registros de ensayos y fuentes de literatura gris. Además, se hicieron búsquedas en MEDLINE, Embase, PsycINFO, CINAHL, LILACS, Web of Science Core Collection, ClinicalTrials.gov y en el World Health Organization's trials portal, ICTRP, para garantizar que las búsquedas sean exhaustivas y actualizadas.
Criterios de selección
Se incluyeron los ensayos controlados aleatorios (ECA) que describieron intervenciones para los pacientes con demencia leve a moderada y compararon el EC versus un control o una intervención alternativa.
Obtención y análisis de los datos
Si fue necesario, se extrajeron los datos relevantes de los manuscritos publicados y mediante contacto con los autores de los ensayos. Se evaluó el riesgo de sesgo de los estudios mediante la herramienta Cochrane "Riesgo de sesgo". Las condiciones de comparación se dividieron en condiciones activas o pasivas y tratamientos alternativos. Se utilizó una gran cantidad de medidas y datos para evaluar 19 resultados al final del tratamiento, así como 16 resultados al seguimiento a medio plazo; esta información se agrupó en metanálisis. Los cálculos agrupados del efecto del tratamiento se realizaron mediante un modelo de efectos aleatorios, y la heterogeneidad estadística se calculó mediante la prueba estadística estándar de ji². Se calificó la evidencia utilizando GradePro.
Resultados principales
Los 33 ensayos incluidos se publicaron entre 1988 y 2018 y se realizaron en 12 países; en su mayoría fueron ECA no registrados, de grupos paralelos y en centros únicos, y las muestras variaron entre 12 y 653 participantes. Las intervenciones duraron entre dos y 104 semanas. La mayoría de las intervenciones experimentales se clasificaron como "EC directo", pero algunas se clasificaron como "EC ampliado", y cerca de dos tercios como intervenciones multidominio. Los investigadores investigaron 18 condiciones control pasivas y 13 activas, junto con 15 condiciones de tratamiento alternativas, que incluyen terapia ocupacional, conciencia plena, terapia de reminiscencia y otros.
La calidad metodológica de los estudios varió, pero se valoró que casi todos los estudios tuvieron riesgo alto o incierto de sesgo de selección debido a la falta de ocultación de la asignación y riesgo alto o incierto de sesgo de realización debido a la falta de cegamiento de los participantes y el personal.
Se utilizaron los datos de 32 estudios en el metanálisis de al menos un resultado. En relación con una condición control, se encontró evidencia de calidad moderada que mostró un efecto pequeño a moderado del EC en el primer resultado primario, la medida compuesta de cognición global al final del tratamiento (diferencia de medias estandarizada [DME] 0,42; intervalo de confianza [IC] del 95%: 0,23 a 0,62), así como evidencia de alta calidad que mostró un efecto moderado sobre el resultado secundario fluencia semántica verbal (DME 0,52; IC del 95%: 0,23 a 0,81) al final del tratamiento, y estas ganancias se mantuvieron a medio plazo (tres a 12 meses después del tratamiento). Con relación a muchos otros resultados, incluido el segundo resultado primario de gravedad de la enfermedad clínica a medio plazo, la certeza de la evidencia fue muy baja, por lo que no fue posible determinar si el EC se asoció con cualquier ganancia significativa.
En comparación con un tratamiento alternativo, se encontró que el EC podría tener poco a ningún efecto sobre el primer resultado primario de cognición global al final del tratamiento (DME 0,21; IC del 95%: ‐0,23 a 0,64), pero la certeza de la evidencia fue baja. No hubo evidencia disponible para evaluar el segundo resultado primario de gravedad clínica de la enfermedad a medio plazo. Se encontró evidencia de calidad moderada que indicó que el EC se asoció con un mejor estado de ánimo del cuidador al final del tratamiento, pero este hallazgo se basó en un único ensayo. La certeza de la evidencia con relación a muchos otros resultados al final del tratamiento y a medio plazo fue demasiado baja para poder determinar si el EC se asoció con cualquier ganancia, pero existe certeza moderada de que el EC no dio lugar a cualquier ganancia en los síntomas del estado de ánimo, conductuales y psicológicos, ni en la capacidad para realizar las actividades cotidianas.
Conclusiones de los autores
En relación con una intervención control, pero no con varios tratamientos alternativos, el EC probablemente se asocia con efectos positivos pequeños a moderados sobre la cognición global y la fluidez semántica verbal al final del tratamiento, y al parecer estos efectos beneficiosos se mantienen a medio plazo. La certeza con relación a muchos de estos resultados es baja o muy baja. Los estudios futuros deben tomar medidas más fuertes para mitigar los riesgos bien establecidos de sesgo y deben proporcionar seguimiento a largo plazo para mejorar la comprensión del grado en el que se mantienen las ganancias observadas. Los ensayos futuros también se deben centrar en la comparación directa del EC versus tratamientos alternativos, en lugar de condiciones control pasivas o activas.
PICO
Resumen en términos sencillos
Entrenamiento cognitivo para pacientes con demencia leve a moderada
Antecedentes
La demencia debida a Alzheimer y otras enfermedades es una causa principal de discapacidad y un enorme problema social y de salud. Más de 40 000 000 de personas en el mundo viven actualmente con demencia y se espera que este número aumente a más de 115 000 000 en el año 2050. Se necesitan con urgencia tratamientos efectivos para reducir la carga de la demencia. El entrenamiento cognitivo (EC) es una forma de tratamiento no farmacológico que se centra en la práctica guiada en tareas dirigidas a funciones cognitivas específicas como la memoria, la atención o la solución de problemas. Aún no está claro si la EC puede ayudar a los pacientes con demencia leve a moderada a mantener o mejorar sus pensamientos, su bienestar y el funcionamiento general.
Principales hallazgos
Se analizaron los datos de 33 estudios de EC que incluyeron en total aproximadamente 2000 participantes y se realizaron en 12 países. Se encontró que, en comparación con recibir tratamiento habitual u ocuparse de actividades no específicas, los pacientes que realizaron el EC pueden mostrar algunos efectos beneficiosos en la cognición general, así como en capacidades cognitivas más específicas como la fluidez verbal, y que las mejoras pueden durar al menos unos pocos meses. No se encontró evidencia de que la participación en el EC se asociara con un aumento de la carga para los participantes. Sin embargo, tampoco se encontró evidencia de que el EC fuera mejor que la participación en otros tratamientos activos.
Limitaciones de esta revisión
La calidad de los estudios que se examinaron varió, pero en general no fue muy alta, por lo que la certeza en algunos de estos hallazgos es baja. Los estudios futuros deben mejorar su calidad, comparar el EC con otros tratamientos y seguir a los participantes durante un período más largo para comprender si los efectos beneficiosos observados para la cognición duran más allá del corto o medio plazo.
Conclusiones de los autores
Summary of findings
| Cognitive training compared to control immediately post intervention for people with mild to moderate dementia | ||||||
| Patient or population: people with mild to moderate dementia | ||||||
| Outcomes | Anticipated absolute effects* (95% CI) | Relative effect | No. of participants | Certainty of the evidence | Comments | |
| Risk with control immediately post intervention | Risk with cognitive training | |||||
| Change in a global measure of cognition (composite) | Mean change in a global measure of cognition (composite) was 0 | SMD 0.42 higher | ‐ | 1389 | ⊕⊕⊕⊝ | Cognitive training probably has a modest effect on global cognition (based on a composite score) |
| Change in a global measure of cognition | Mean change in a global measure of cognition was 0 | SMD 0.65 higher | ‐ | 1288 | ⊕⊕⊝⊝ | Cognitive training may have a moderate effect on performance in global cognition (based on a screening measure). |
| Change in delayed memory | Mean change in delayed memory was 0 | SMD 0.81 higher | ‐ | 543 | ⊕⊝⊝⊝ | We are unable to determine whether there is any effect on delayed memory due to the very low quality of evidence |
| Change in participants' mood | Mean change in participants' mood was 0 | SMD 0.72 higher | ‐ | 577 | ⊕⊝⊝⊝ | We are unable to determine whether there is any effect on participants' mood due to the very low quality of evidence |
| Change in capacity for activities of daily living | Mean change in capacity for activities of daily living was 0 SD | SMD 0.12 SD higher | ‐ | 687 | ⊕⊕⊝⊝ | Cognitive training may not have an effect on capacity for activities of daily living |
| Participant burden (retention rates) | Study population | OR 0.73 | 1282 | ⊕⊕⊝⊝ | Cognitive training may not be associated with an increase in participant burden as reflected in retention rates | |
| 908 per 1000 | 878 per 1000 | |||||
| Change in mood and well‐being (caregiver) | Mean change in mood and well‐being (caregiver) was 0 | SMD 0.98 higher | ‐ | 36 | ⊕⊕⊕⊝ | Cognitive training probably has a large effect on mood and well‐being in the caregiver |
| *The risk in the intervention group (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI). | ||||||
| GRADE Working Group grades of evidence. | ||||||
| aInconsistency: downgraded 1 point for serious concerns regarding heterogeneity in effect size, which is moderate and statistically significant. Heterogeneity does not seem to be well explained by investigated effect moderators. bInconsistency: downgraded 2 points for very serious concerns regarding heterogeneity in effect size, which is relatively large and statistically significant. Heterogeneity does not seem to be well explained by investigated effect moderators. cPublication bias: downgraded 1 point for strongly suspected publication bias based on visual inspection of the funnel plot, raising the possibility that small negative studies may remain unpublished. dImprecision: downgraded 1 point for serious concerns related to imprecision because the confidence interval crosses the no treatment threshold. eImprecision: downgraded 2 points for very serious concerns related to imprecision because the confidence interval includes positive effect, negligible effect, and effect in the direction of the control group. fRisk of bias: outcome estimation is based on a single study with several limitations related to unclear or high risk of bias in several domains. gImprecision: downgraded 1 point for serious concerns related to imprecision because the analysis is based on fewer than 400 participants; however the confidence interval does not cross the no effect threshold. | ||||||
| Cognitive training compared to control in the medium term (3 to 12 months post intervention) for people with mild to moderate dementia | ||||||
| Patient or population: people with mild to moderate dementia | ||||||
| Outcomes | Anticipated absolute effects* (95% CI) | Relative effect | No. of participants | Certainty of the evidence | Comments | |
| Risk with control in the medium term (3 to 12 months post intervention) | Risk with cognitive training | |||||
| Change in a global measure of cognition (composite) | Mean change in a global measure of cognition (composite) was set at 0 SDs | SMD 0.65 higher | ‐ | 387 | ⊕⊝⊝⊝ | We are unable to determine whether there is any effect on global cognition (composite) due to the very low quality of evidence |
| Change on global cognition (screening) (Global cog) | Mean change in global cognition (screening) was set at 0 SDs | SMD 1.33 higher | ‐ | 387 | ⊕⊝⊝⊝ | We are unable to determine whether there is any effect on performance in global cognition due to the very low quality of evidence |
| Change in disease progression | Mean change in disease progression was set at 0 SDs | SMD 0.55 higher | ‐ | 98 | ⊕⊝⊝⊝ | We are unable to determine whether CT slows down disease progression due to the very low quality of evidence |
| Change in delayed memory | Mean change in delayed memory was set at 0 SDs | SMD 0.97 SD higher | ‐ | 253 | ⊕⊝⊝⊝ | We are unable to determine whether there is any effect on performance in delayed memory due to the very low quality of evidence |
| Change in capacity for activities of daily living | Mean change in capacity for activities of daily living was set at 0 SDs | SMD 0.22 higher | ‐ | 64 | ⊕⊕⊝⊝ | Cognitive training may not have an effect on capacity for activities of daily living |
| Change in participants' mood | Mean change in participants' mood was set at 0 SDs | SMD 0.21 higher | ‐ | 30 | ⊕⊕⊝⊝ | Cognitive training may not have an effect on participants' mood |
| Change in mood and well‐being (caregiver) | ‐ | See comment | ‐ | (0 studies) | ‐ | No studies have evaluated this outcome in the intermediate term |
| *The risk in the intervention group (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI). | ||||||
| GRADE Working Group grades of evidence. | ||||||
| aRisk of bias: downgraded 2 points for very serious concerns related to risk of bias: removal of high‐risk studies leads to reasonably large changes in the effect estimate. bInconsistency: downgraded 1 point for serious concerns regarding heterogeneity in effect size, which is large and statistically significant. However, heterogeneity seems to be partially explained by investigated effect moderators. cImprecision: downgraded 2 points for very serious concerns related to imprecision because the analysis is based on fewer than 400 participants, and the confidence interval crosses the no effect threshold. dInconsistency: downgraded 2 points for very serious concerns regarding heterogeneity in effect size, which is relatively large and statistically significant. Heterogeneity does not seem to be well explained by investigated effect moderators. eImprecision: downgraded 1 point for serious concerns related to imprecision because the analysis is based on fewer than 400 participants; however the confidence interval does not cross the no effect threshold. | ||||||
| Cognitive training compared to alternative treatment immediately post intervention for people with mild to moderate dementia | ||||||
| Patient or population: people with mild to moderate dementia | ||||||
| Outcomes | Anticipated absolute effects* (95% CI) | Relative effect | No. of participants | Certainty of the evidence | Comments | |
| Risk with alternative treatment immediately post intervention | Risk with cognitive training | |||||
| Change in a global measure of cognition (composite) | Mean change in a global measure of cognition (composite) was 0 SD | SMD 0.21 SD higher | ‐ | 769 | ⊕⊕⊝⊝ | Cognitive training may not have an effect on global cognition |
| Change in a global measure of cognition | Mean change in a global measure of cognition was 0 | SMD 0.16 higher | ‐ | 724 | ⊕⊝⊝⊝ | We are unable to determine whether there is any effect on global cognition (as measured by a screening tool) due to very low quality of evidence |
| Change in delayed memory | Mean change in delayed memory was 0 | SMD 0.71 higher | ‐ | 147 | ⊕⊝⊝⊝ | We are unable to determine whether there is any effect on performance in delayed memory due to very low quality of the evidence |
| Change in participants' mood | Mean change in participants' mood was 0 | SMD 0.11 lower | ‐ | 543 | ⊕⊕⊕⊝ | Cognitive training probably has no effect on participants' mood |
| Change in capacity for activities of daily living | Mean change in capacity for activities of daily living was 0 | SMD 0.25 lower | ‐ | 525 | ⊕⊕⊕⊝ | Cognitive training probably has no effect on capacity for activities of daily living |
| Participant burden (retention rates) | Study population | OR 0.78 | 639 | ⊕⊝⊝⊝ | We are unable to determine whether cognitive training increases participant burden (as measured by retention rates) | |
| 773 per 1000 | 727 per 1000 | |||||
| Change in mood and well‐being (caregiver) | Mean change in mood and well‐being (caregiver) was 0 | SMD 1.5 higher | ‐ | 88 | ⊕⊕⊕⊝ | Cognitive training probably has a large effect on mood and well‐being in the caregiver |
| *The risk in the intervention group (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI). | ||||||
| GRADE Working Group grades of evidence. | ||||||
| aImprecision: downgraded 2 points for very serious concerns related to imprecision because the confidence interval includes positive effect, negligible effect, and effect in the direction of the control group. bInconsistency: downgraded 1 point for serious concerns regarding heterogeneity in effect size, which is moderate and statistically significant. Heterogeneity does not seem to be well explained by investigated effect moderators. cInconsistency: downgraded 2 points for very serious concerns regarding heterogeneity in effect size, which is relatively large and statistically significant. Heterogeneity does not seem to be well explained by investigated effect moderators. dImprecision: downgraded 2 points for very serious concerns related to imprecision because the analysis is based on fewer than 400 participants, and the confidence interval crosses the no effect threshold. eImprecision: downgraded 1 point for serious concerns related to imprecision because the sample size includes fewer than 400 participants. | ||||||
| Cognitive training compared to alternative treatment in the medium term (3 to 12 months post intervention) for people with mild to moderate dementia | ||||||
| Patient or population: people with mild to moderate dementia | ||||||
| Outcomes | Anticipated absolute effects* (95% CI) | Relative effect | No. of participants | Certainty of the evidence | Comments | |
| Risk with alternative treatment in the medium term (3 to 12 months post intervention) | Risk with cognitive training | |||||
| Change in a global measure of cognition (composite) | Mean change in a global measure of cognition (composite) was set at 0 SDs | SMD 1.31 SD higher | ‐ | 73 | ⊕⊝⊝⊝ | We are unable to determine whether there is any effect on global cognition (composite) due to very low quality of the evidence |
| Change in a global measure of cognition | Mean change in a global measure of cognition was set at 0 SDs | SMD 3.2 higher | ‐ | 73 | ⊕⊝⊝⊝ | We are unable to determine whether there is any effect on performance in a screening measure of global cognition due to very low quality of the evidence |
| Change in disease progression | ‐ | See comment | ‐ | (0 studies) | ‐ | None of the included studies have evaluated this outcome |
| Change in delayed memory | Mean change in delayed memory was set at 0 SDs | SMD 3.13 higher | ‐ | 73 | ⊕⊝⊝⊝ | We are unable to determine whether there is any effect on performance in delayed memory due to very low quality of the evidence |
| Change in participants' mood | Mean change in participants' mood was set at 0 SDs | SMD 0.66 lower | ‐ | 39 | ⊕⊕⊝⊝ | Cognitive training may not have an effect on a participants' mood |
| Change in capacity for activities of daily living | ‐ | See comment | ‐ | (0 studies) | ‐ | None of the included studies have evaluated this outcome |
| Change in mood and well‐being (caregiver) | ‐ | See comment | ‐ | (0 studies) | ‐ | None of the included studies have evaluated this outcome |
| *The risk in the intervention group (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI). | ||||||
| GRADE Working Group grades of evidence. | ||||||
| aImprecision: downgraded 2 points for very serious concerns related to imprecision because the confidence interval includes positive effect, negligible effect, and effect in the direction of the control group. | ||||||
Antecedentes
Descripción de la afección
La demencia es un síndrome clínico en el que se compromete la independencia funcional debido a la deficiencia intelectual y cognitiva (principalmente de aparición gradual). La demencia es causada con frecuencia por procesos fisiopatológicos relacionados con la edad. La enfermedad de Alzheimer (EA) y la EA y la enfermedad cerebrovascular combinadas son las causas más frecuentes de demencia en los pacientes mayores (Alzheimer's Association 2018). Otras causas frecuentes incluyen la patología con cuerpos de Lewy (en la demencia con cuerpos de Lewy [DCL] y en la demencia por enfermedad de Parkinson [DEP]) y la degeneración lobular frontotemporal (en las demencias frontotemporales [DFT]); hay muchas otras causas mucho menos frecuentes) (Alzheimer's Disease International 2009).
La demencia debida a la mayoría de las afecciones neurodegenerativas se asocia por lo general con agregados de proteínas plegadas o mal plegadas (Villemagne 2018). En el caso de la demencia debida a la EA, se incluyen los agregados de proteína Aβ que forman placas en el espacio entre las neuronas, así como los agregados de proteína tau mal plegada que forma ovillos neurofibrilares dentro de las neuronas. Otros agregados proteicos están implicados en otras enfermedades neurodegenerativas (p.ej. TDP‐43 en la FTD, agregados de proteína alfa sinucleína alfa en la demencia con cuerpos de Lewy). Las enfermedades de proteínas agregadas se diseminan por lo general de una manera previsible y bien descrita por las regiones corticales y subcorticales (Braak & Braak 2012). En el caso de la mayoría de las etiologías de la demencia, la serie fisiopatológica de eventos comienza años o incluso décadas antes de la aparición de los síntomas clínicos obvios, y en estos estadios los pacientes buscan cada vez más la atención clínica (Alzheimer's Association 2018).
Independientemente de la causa, la demencia tiene por lo general una aparición insidiosa y un curso progresivo (aunque en algunos casos, p.ej. la deficiencia cognitiva vascular, se puede observar una aparición más rápida) (Wilson 2012). Aunque el cuadro clínico en los estadios iniciales o leves puede variar según la etiología de la enfermedad subyacente, la deficiencia cognitiva global, los cambios en la personalidad y el comportamiento, así como la independencia funcional comprometida, son características comunes cuando se produce la progresión clínica. La deficiencia cognitiva (en el caso de la EA y la enfermedad vascular) y los cambios conductuales, de la personalidad y el lenguaje (en el caso de la neurodegeneración frontotemporal) por lo general están presentes mucho antes de que se haga el diagnóstico clínico, pero en estadios iniciales pueden ser difíciles de diferenciar de los cambios habituales relacionados con la edad, o de los síntomas asociados con afecciones psiquiátricas frecuentes (p.ej. la depresión), un factor que a menudo da lugar a que se retrase la búsqueda de atención médica. Durante la fase predemencia, los pacientes se presentan generalmente con deficiencia cognitiva leve durante un período en el cual la deficiencia cognitiva se puede detectar con el examen formal (Albert 2011; Petersen 2004), pero el paciente no muestra deficiencia en la capacidad para realizar la mayoría de las actividades cotidianas, o esta es mínima. En los estadios de la demencia leve a moderada, la deficiencia cognitiva se hace más profunda y la discapacidad funcional generalizada se hace cada vez más evidente, en particular con relación a las actividades más complejas, y la carga de los cuidadores tiende a aumentar de manera significativa (Berger 2005; Gaugler 2000). En los estadios más avanzados de la demencia, la mayoría de las capacidades cognitivas y funcionales están profundamente afectadas y con frecuencia se observan cambios conductuales como la apatía, la depresión, la agresión y la agitación (Förstl 1999).
A pesar de alguna superposición, a menudo es posible distinguir la firma de síntomas cognitivos que caracteriza las diferentes etiologías de la enfermedad que tienden a convertirse en demencia, al menos en los estadios iniciales. En el caso de la demencia debida a EA, los signos cognitivos más tempranos en el examen neuropsicológico formal se relacionan casi invariablemente con la función de la memoria episódica. Dentro del dominio de la memoria, los déficit más sorprendentes se observan por lo general en las medidas del nuevo aprendizaje y la memoria diferida, déficits que preceden en viarios años al diagnóstico de la EA (Weintraub 2012). Una vez que se han desarrollado los déficits en las medidas del aprendizaje y la memoria, los pacientes a menudo muestran mayores dificultades para cumplir con las tareas relacionadas con la memoria semántica, el lenguaje, las funciones ejecutivas y las capacidades visuoespaciales/constructivas. En la demencia con cuerpos de Lewy es más probable que las deficiencias cognitivas tempranas incluyan déficits visuoespaciales sorprendentes, fluctuación de la atención y una disminución de la capacidad de trabajo de la memoria, junto con el desarrollo de alucinaciones intensas. En las demencias relacionadas con la degeneración lobular frontotemporal, los primeros síntomas pueden ser predominantemente conductuales y pueden estar relacionados con la cognición social en la variante conductual de la DFT, o los subtipos temporales pueden incluir predominantemente las habilidades del lenguaje y la expresión verbal (Weintraub 2012). Aunque el deterioro del rendimiento en las medidas de la memoria episódica es fundamental en la demencia vascular, los pacientes con esta afección muestran habitualmente un déficit más sorprendente en las tareas ejecutivas y de atención, así como en medidas del conocimiento semántico y la función visuoespacial (Graham 2004).
La demencia es muy prevalente en los pacientes de edad avanzada, es una causa principal de discapacidad en todo el mundo y se asocia con una enorme carga económica, emocional y social (Wimo 2017), lo que hace que los estudios de investigación en esta área sean una prioridad global (World Health Organization 2012). A pesar de años de investigación y numerosos ensayos clínicos, aún no hay una cura disponible para cualquiera de las causas irreversibles de la demencia. Los inhibidores de la colinesterasa son todavía el tratamiento farmacológico primario para los síntomas cognitivos en la EA y las demencias relacionadas; sin embargo, los efectos de estos fármacos no son universales y siempre son temporales (Birks 2006). Están disponibles varias intervenciones no farmacológicas (INF) dirigidas a diferentes aspectos del síndrome clínico, la discapacidad asociada y la carga de los cuidadores (para una revisión sistemática integral, ver Olazaran 2010). En general, las INF no son específicas de la enfermedad y no se relacionan directamente con los objetivos biológicos subyacentes; por lo tanto, no son "modificadores de la enfermedad" Por otro lado, es más probable que las INF se dirijan a un espectro más amplio de resultados clínicamente significativos y es menos probable que causen reacciones adversas. Dentro de la amplia categoría de las INF, los tratamientos dirigidos a la cognición, en particular el EC, han sido un tema de mucho interés entre los investigadores, los médicos y el público general.
Descripción de la intervención
"Tratamientos dirigidos a la cognición" (TDC), llamados previamente "intervenciones dirigidas a la cognición" (Clare 2002; Clare 2004), es un término general que se refiere a un grupo de INF en las que se aplican varias técnicas para vincular el pensamiento y la cognición a diversos grados de amplitud y la especificidad. A diferencia de las INF, que se dirigen principalmente hacia resultados conductuales (p.ej. la deambulación), emocionales (p.ej. la ansiedad), o físicos (p.ej. el estilo de vida sedentario), en los TDC las metas incluyen mejorar o mantener los procesos cognitivos o abordar la repercusión de la deficiencia en los procesos cognitivos sobre la capacidad funcional asociada a la vida cotidiana (Bahar‐Fuchs 2013; Clare 2004). El EC, en ocasiones descrito en la bibliografía como "entrenamiento cerebral", "reentrenamiento" o "rehabilitación", incluye con frecuencia la práctica guiada de un conjunto de tareas estructuradas y habitualmente estandarizadas, diseñadas para entrenar a individuos en procesos y capacidades cognitivos relativamente bien definidos como la velocidad de procesamiento de la información, la atención, la memoria o la solución de problemas (Bahar‐Fuchs 2013; Mowszowski 2010). Otros TDC descritos en la bibliografía incluyen el tratamiento de estimulación cognitiva (TEC) y la rehabilitación cognitiva (RC); estos enfoques se consideran diferentes con respecto a los supuestos teóricos y los aspectos fundamentales, así como a los contextos o las poblaciones en los que se han aplicado tradicionalmente, pero se reconoce que existe cierta superposición y que la diferenciación entre estos enfoques no siempre es directa (Bahar‐Fuchs 2013; Gates 2014). De hecho, estos términos se han aplicado y aún se aplican de manera indistinta en la bibliografía (p.ej. Fernandez‐Prado 2012; Giordano 2010), a pesar de la disponibilidad de definiciones y descripciones amplias de estas formas diferentes de intervención (Bahar‐Fuchs 2013; Clare 2004; Woods 2012). La tabla 1 (más adelante) resume las características definitorias clave y las propiedades comunes de estos enfoques. La estimulación cognitiva es el foco de otra revisión Cochrane, que concluyó que la estimulación cognitiva general produce de manera consistente mejorías en la cognición general y, en algunos casos, en la calidad de vida y el bienestar autoinformados, principalmente para los pacientes con demencia leve a moderada (Woods 2012). La rehabilitación cognitiva, que es un enfoque intrínsecamente individualizado que recalca la fijación de metas colaborativas con una orientación funcional (Bahar‐Fuchs 2016; Clare 2001), se consideró junto con el EC en las versiones anteriores de esta revisión Cochrane (Bahar‐Fuchs 2013; Clare 2004); sin embargo, como el conjunto de la evidencia para este enfoque ha aumentado en años recientes, e incluye métodos diferentes y se dirige a diferentes resultados, la rehabilitación cognitiva se considerará en otra revisión Cochrane, por lo que la revisión actual se centrará solo en el EC.
Entrenamiento cognitivo
El entrenamiento cognitivo (EC) se ha expresado históricamente dentro del campo más amplio de la rehabilitación neuropsicológica de pacientes con lesiones cerebrales y enfermedades neurológicas. Los esfuerzos para reentrenar de manera sistemática funciones cognitivas específicas fueron descritos originalmente por investigadores clínicos como Leonard Diller y Yehuda Ben‐Yishay en su trabajo pionero con víctimas de accidentes cerebrovasculares y traumatismos craneoencefálicos a lo largo de los años setenta (Ben‐Yishay 1978; Diller 1974). A comienzos de los años ochenta, los principios del EC comenzaron a aplicarse en los pacientes de edad avanzada cognitivamente sanos con quejas cognitivas subjetivas (p.ej. Zarit, 1981); sin embargo, no fue hasta finales de los años ochenta que el EC se intentó por primera vez en personas con demencia (p.ej. Beck 1988). Una suposición fundamental que es la base del EC es que la práctica tiene la posibilidad de mejorar o al menos mantener el funcionamiento en un dominio cognitivo determinado. Otra suposición importante es que cualquier efecto de la práctica se generalizará más allá del contexto de entrenamiento inmediato. En otras palabras, la mejoría en el rendimiento en una tarea dada debe dar lugar a un mejor rendimiento en otras tareas relacionadas que dependen del mismo proceso o capacidad cognitivos. Aunque a menudo la evidencia no ha apoyado esta última suposición (Owen 2010; Papp 2009), algunos han alegado que la imposibilidad de producir efectos beneficiosos transferibles se relaciona en parte con los problemas en el diseño de las tareas (Jaeggi 2010). Como se señaló anteriormente, el EC ha incluido tradicionalmente la práctica repetida de un conjunto de tareas estructuradas diseñadas hacia procesos y capacidades cognitivos particulares. Algunos autores de estudios han propuesto que el EC se debe dividir en subtipos de ejercicios cognitivos y estrategias de entrenamiento (Gates 2011); estas últimas incluyen la instrucción y la práctica en el uso de estrategias cognitivas específicas diseñadas para mejorar de manera adicional el rendimiento o para disminuir la repercusión del deterioro de la cognición (p.ej. método de lugares, imágenes visuales) (Hampstead 2016). El EC difiere del tipo de entrenamiento en habilidades administrado a menudo por terapeutas ocupacionales, en que el objetivo es por lo general un proceso o una capacidad subyacente, en lugar de una habilidad específica. Las versiones tempranas del EC tendieron a administrarse como un enfoque "genérico"; sin embargo, en años recientes los adelantos tecnológicos han dado lugar a una mayor adaptación del foco de entrenamiento sobre la base del perfil cognitivo individual y el nivel de dificultad adaptativa (Bahar‐Fuchs 2017; Peretz 2011). El EC se puede ofrecer mediante sesiones individuales (Davis 2001; de Vreese 1998a; de Vreese 1998b; Farina 2002; Koltai 2001; Loewenstein 2004), sesiones grupales (Cahn‐Weiner 2003; Ermini Fuenfsch 1995; Kesslak 1997; Koltai 2001; Moore 2001), o puede ser facilitado por miembros de la familia con apoyo de los terapeutas (Neely 2009; Quayhagen 1995a; Quayhagen 2000). Inicialmente se administró principalmente en formato de lápiz y papel, pero durante las dos últimas décadas los programas de entrenamiento cognitivo computarizado (ECC) han reemplazado en gran parte los métodos más tradicionales (Davis 2001; de Vreese 1998; Quayhagen 1995; Quayhagen 2000). En algunos casos, las tareas o actividades que forman el foco de la práctica/el entrenamiento son análogos a las actividades diarias reales, como hacer compras en línea o montar una mesa para la cena (Farina 2002; Loewenstein 2004; Neely 2009; Zanetti 1994; Zanetti 1997; Zanetti 2001), y en estos casos la distinción entre EC y entrenamiento de habilidades funcionales se hace más difícil. Las intervenciones dirigidas a las habilidades, en las que la tarea objetivo está bien estructurada y dividida en elementos de rendimiento cognitivo subyacentes y relativamente bien definidos, y en las que los resultados de interés son los procesos cognitivos en lugar de solo el rendimiento de la propia tarea de intervención (p.ej. Neely 2009), parecen ajustarse al marco conceptual del EC. Por el contrario, cuando el foco de la intervención es una habilidad específica y no hay expectativa alguna de mejorar una capacidad/proceso cognitivo fundamental, y cuando las bases cognitivas están poco claras o solo se abordan de una manera vaga, la intervención se podría clasificar mejor como "entrenamiento de habilidades funcionales" De acuerdo con la sugerencia de que el EC puede mejorar los efectos del tratamiento farmacológico (Newhouse 1997), algunos estudios han evaluado la eficacia del EC en combinación con el uso de inhibidores de la colinesterasa (Cahn‐Weiner 2003; de Vreese 1998a; de Vreese 1998b; Loewenstein 2004), o administrado con otros fármacos (Heiss 1993; Yesavage 1981).
| Table 1. Selected characteristics of cognitive training, rehabilitation, and stimulation | |||
| Cognitive training | Cognitive rehabilitation | Cognitive stimulation | |
| Target | Impairment | Participation restriction | Participation restriction |
| Context | Structured tasks and environments | The person’s natural environment | Usually a clinic/residential care or daycare setting |
| Focus of intervention | Specific cognitive abilities and processes; psychoeducation and strategy training sometimes included | Groups of cognitive abilities and processes required to perform individually relevant everyday tasks; behaviour, environment, and everyday activity. Psychoeducation and strategy training sometimes included | Orientation, global cognitive status |
| Format | Individualised or group | Individualised | Typically group |
| Proposed mechanism of action | Mainly restorative; mechanisms related to neuroplasticity | Combination of restorative and compensatory approaches; reduction of 'excess disability' | Improved orientation; general activation |
| Goals | Improved or maintained ability in specific cognitive domains | Performance and functioning in relation to collaboratively set behavioural or functional goals | Improved overall orientation and engagement in pleasant abilities |
De qué manera podría funcionar la intervención
El entrenamiento cognitivo (EC) intenta mejorar o mantener procesos cognitivos específicos o capacidades cognitivas generales; cuando se utiliza como un enfoque de intervención en las poblaciones clínicas, se espera que las mejorías en la cognición se generalizarán a la mejoría en los resultados funcionales. Mucho se ha escrito acerca de la falta de unificación de las teorías en el campo de las INF, incluidas las relacionadas con las intervenciones dirigidas a cambiar el comportamiento (Michie 2008), con relación a la cognición y la función (Wilson 2002), y con relación a la rehabilitación en general (Hart 2014). De hecho, no hay una teoría única que explique de manera integral los aspectos acerca de por qué o cómo el EC debería dar lugar a mejores resultados cognitivos y funcionales; si, y por qué, es más probable que algunos dominios cognitivos respondan al entrenamiento comparados con otros; si el entrenamiento se debe dirigir a dominios cognitivos únicos o a múltiples dominios; o si el entrenamiento se debe centrar en mejorar las funciones deterioradas o centrarse en las preservadas. A diversos grados, las intervenciones de EC en poblaciones saludables y clínicas utilizan en cambio varias teorías y descubrimientos basados en las neurociencias cognitivas (p.ej. Jaeggi 2008; Sohlberg 1987), o en la práctica clínica y la rehabilitación de los pacientes con lesiones y enfermedades neurológicas (Ponsford 2012; Stuss 1999); El EC continúa modificándose en respuesta a los adelantos tecnológicos relevantes, incluidos los informados en la industria de juego (Anguera 2015). Desafortunadamente, muchas intervenciones de EC se han desarrollado y todavía se desarrollan sin una referencia clara a cualquier trabajo teórico relevante.
Una suposición fundamental sostenida por muchos partidarios del EC es que el entrenamiento en una capacidad o proceso cognitivo fundamental dará lugar a mejorías generalizadas que van más allá del contexto del entrenamiento (Lampit 2014). En los pacientes más jóvenes y de mayor edad sanos, y en menor grado en los pacientes con deficiencia cognitiva leve (DCL), existen algunas dudas con respecto a si el EC da lugar a mejorías en las tareas o el "criterio" entrenados. Sin embargo, en las poblaciones sanas y clínicas, la evidencia en cuanto a la transferencia del aprendizaje aún es mixta y el tema es motivo de gran debate, gran parte del mismo relacionado con la identificación de las barreras y los facilitadores de la transferencia de las ganancias a las tareas no entrenadas, que reflejan el dominio cognitivo objetivo del entrenamiento (transferencia cercana) y otros dominios cognitivos no entrenados, así como los resultados no cognitivos (transferencia a distancia) (Jaeggi 2010). En una revisión integral crítica y reciente de la industria comercial del EC, Simons y colegas señalaron que la discusión en cuanto a la transferencia del aprendizaje se puede remontar a consideraciones teóricas muy tempranas (Simons 2016), como la denominada teoría de la disciplina formal y la teoría de la transferencia por elementos idénticos propuesta por Edward Thorndike a principios del siglo XX. Analizar estas teorías en detalle va más allá del alcance de esta revisión, pero la revisión de Simons y colegas incluye una exposición crítica de estas consideraciones con relación a la bibliografía del EC y la industria (Simons 2016). Resultados empíricos contemporáneos indican que los factores que parecen estar implicados en la transferencia de las ganancias relacionadas con el EC incluyen el grado de semejanza o superposición entre los elementos de las tareas de transferencia y entrenadas, el grado de ganancia real con las tareas entrenadas, las capacidades cognitivas iniciales y la edad (Zinke 2014).
Además de las teorías del aprendizaje y la transferencia, el conocimiento y la pericia relacionados con las relaciones entre el cerebro y el comportamiento, así como los mecanismos de las lesiones, las enfermedades y la recuperación, son fundamentales para informar el desarrollo de los TDC, incluido el EC, en el contexto del trabajo con pacientes con trastornos del sistema nervioso central adquiridos (incluida la lesión cerebral traumática, el accidente cerebrovascular y las afecciones neurodegenerativas). Históricamente estas intervenciones han reflejado dos marcos conceptuales amplios para la recuperación de la función después de las enfermedades o las lesiones cerebrales: un enfoque restaurativo y un enfoque contextualizado o compensatorio (Ylvisaker 2002). Por lo general, las técnicas asociadas con la rehabilitación cognitiva, como la optimización de las capacidades cognitivas residuales en los dominios con deterioro y el máximo aprovechamiento de las capacidades cognitivas no deterioradas, se prestan más a los enfoques compensatorios (Clare 2001b). Por contraste, las técnicas asociadas generalmente con el EC, como el ejercicio repetido de pruebas cognitivas estandarizadas con dificultad creciente y el tratamiento dirigido a dominios cognitivos específicos, tienden a reflejar los principios restaurativos y "prosperar en el atractivo de la neuroplasticidad" (Rabipour & Raz 2012). De hecho, varias observaciones relacionadas con la neuroplasticidad en estudios realizados en animales y seres humanos, incluidos los cambios a niveles moleculares, sinápticos, estructurales y funcionales asociados con ambientes enriquecidos y un programa de entrenamiento estructurado, son por lo común citadas como mecanismos de acción propuestos para el EC (Valenzuela 2012). En años recientes, la evidencia creciente ha indicado que el EC se asocia con cambios en los modelos de la activación neural en regiones cerebrales clave de los pacientes de mayor edad saludables (Belleville 2014), así como en los pacientes con DCL (Belleville 2011; Hampstead 2011). Este aumento de la activación cerebral puede ser resultado de los procesos de crecimiento y reparación sinápticos desencadenados mediante la práctica repetida de pruebas estandarizadas.
Por qué es importante realizar esta revisión
Los proyectos de desarrollo de fármacos para la enfermedad de Alzheimer son lentos, y los ensayos de tratamientos modificadores de la enfermedad no han logrado en general producir mejorías en cualquier resultado clínicamente significativo, aunque han tenido éxito en la interrupción de los procesos fisiopatológicos objetivo (Cummings 2014; Cummings 2016; Salomone 2012), lo que ha dado lugar a que algunos cuestionen la relevancia de la hipótesis de la cascada amiloide dominante cuando se refiere al desarrollo de un tratamiento eficaz para la demencia como un síndrome clínico (D'Alton 2011). Las INF que tienen como objetivo desarrollar maneras de vivir mejor con la demencia, debido en parte a que se dirigen a resultados clínicos relevantes y a la carga de los cuidadores, desempeñan una función cada vez más importante en el tratamiento de la demencia y se reconocen como un complemento importante, e incluso alternativo, a los tratamientos farmacológicos disponibles. Una Lancet Commission on Dementia Prevention, Intervention, and Care reciente argumentó que algunas INF ya pueden desempeñar una función importante en el control de algunos de los síntomas cognitivos, conductuales y neuropsiquiátricos de la demencia, y señaló los hallazgos positivos para la terapia de estimulación cognitiva y evidencia preliminar en apoyo a la rehabilitación cognitiva (Livingston 2017).
En los pacientes de edad avanzada saludables (Edwards 2017; Lampit 2014), y en los pacientes con DCL (Chandler 2016; Hill 2017), los hallazgos de las revisiones sistemáticas sobre los efectos del EC en los resultados cognitivos y en varios resultados no cognitivos por lo general han sido alentadores, y se comprenden mejor los factores asociados con el aumento de la eficacia de la intervención en el EC. De hecho, las guías de práctica clínica recientemente publicadas para el DCL han clasificado al EC como apoyado por evidencia de nivel C, lo que significa que los médicos pueden recomendar esta forma de intervención (Petersen 2018).
Por otra parte, la mayoría de las revisiones sistemáticas de EC para los pacientes con demencia han producido hasta la fecha resultados en gran parte negativos (p.ej. Bahar‐Fuchs 2013; Hill 2017; pero ver Sitzer 2006). La revisión Cochrane anterior sobre EC para los pacientes con demencia incluyó 11 ensayos controlados aleatorios, pero no proporcionó evidencia para apoyar el EC con respecto a cualquiera de los resultados examinados. Sin embargo, se señaló que la certeza de estos hallazgos puede haber disminuido por el número relativamente pequeño de estudios muy heterogéneos, que a menudo fueron de baja calidad metodológica. En contra del antecedente de una comunidad científica muy dividida y una industria siempre creciente de productos comerciales de EC que en ocasiones hace declaraciones sumamente engañosas, es fundamental que a los médicos, los elaboradores de políticas y el público general se les presente una revisión actualizada, rigurosa y no sesgada de la bibliografía actual sobre el EC para los pacientes con demencia leve a moderada.
Objetivos
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Evaluar los efectos del EC sobre los resultados cognitivos y no cognitivos en los pacientes con demencia leve a moderada y sus cuidadores.
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Comparar los efectos del EC con los de otras intervenciones no farmacológicas, incluida la estimulación o la rehabilitación cognitiva, para los pacientes con demencia leve a moderada y sus cuidadores.
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Identificar y explorar los factores relacionados con la intervención y el diseño de los ensayos que se pueden asociar con la eficacia del EC para los pacientes con demencia leve a moderada y sus cuidadores.
Métodos
Criterios de inclusión de estudios para esta revisión
Tipos de estudios
De acuerdo con la versión anterior de esta revisión, y para asegurar la inclusión de estimaciones no sesgadas de los efectos del tratamiento solo (Reeves 2011), solo se consideraron para inclusión los ensayos controlados aleatorios (ECA). Cuando fue posible, no se excluyeron los estudios publicados en un idioma diferentes del inglés y se hizo todo lo posible para obtener una traducción al inglés de los autores del estudio. En los casos en los que no fue posible obtener una traducción de los autores del estudio, se hicieron esfuerzos razonables para obtener una traducción fiable y el estudio se excluyó solo si estos esfuerzos fueron infructuosos.
Tipos de participantes
Se incluyeron los ensayos en los que todos los participantes habían recibido un diagnóstico médico de demencia de cualquier subtipo, siempre que se supusiera que la etiología fundamental no era reversible. Era de esperar que el diagnóstico de demencia se hiciera en general sobre la base de criterios diagnósticos clínicos o de investigación establecidos, incluidos los siguientes criterios especificados.
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El Diagnostic and Statistical Manual of Mental Disorders, 5a Edición (DSM‐V; APA 2013) o las versiones anteriores (APA 1995).
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La International Classification of Diseases,10a Revisión (ICD‐10) (WHO 1992).
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El National Institute of Neurological and Communicative Disorders and Stroke ‐ Alzheimer's Disease and Related Disorders Association (NINCDS‐ADRDA) (McKhann 1984).
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Los National Institutes of Health ‐ Alzheimer's Association (NIH‐AA) (McKhann 2011).
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La Association Internationale pour la Recherché et l'Enseignement en Neurosciences (NINDS‐AIREN) (Roman 1993).
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El Vascular Impairment of Cognition Classification Consensus Study (McKeith 1996; McKeith 2006; McKeith 2017).
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El International Behavioural Variant FTD Criteria Consortium (FTDC) (Skrobot 2017).
Como promedio, los participantes en los estudios incluidos se clasificaron como con presencia de un nivel leve a moderado de gravedad. En general, la gravedad de la demencia en los ensayos primarios se determinó sobre la base de las puntuaciones medias del grupo, los rangos de las puntuaciones o las puntuaciones individuales en una escala estandarizada, como las puntuaciones sobre 12 en el Mini Mental State Examination (MMSE; Folstein 1975), o las puntuaciones de 0,5 a 2 en la escala Clinical Dementia Rating (CDR 2; Hughes 1982).
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Los estudios en los que estaba claro que solo una proporción pequeña de los participantes (es decir < 15%) se clasificó dentro del rango más grave de demencia o el rango de demencia dudosa se consideraron aceptables si esta información se indicó con claridad en el estudio.
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Los participantes clasificados generalmente residían en el domicilio o en una residencia geriátrica. Se excluyeron los estudios en los que los participantes reclutados podían estar ingresados a largo plazo en hospitales psiquiátricos y en los que era probable que hubiera enfermedades psiquiátricas preexistentes.
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No se establecieron restricciones específicas relacionadas con la edad, aunque era de esperar que, con la excepción de los participantes con demencia de aparición temprana (DAT), la mayoría de los participantes tendrían 65 años de edad o más.
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No se establecieron restricciones con respecto al tratamiento farmacológico actual. Cuando estuvo disponible, se señaló la información acerca de la administración de inhibidores de la colinesterasa a los participantes.
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Los estudios primarios que incluyeron participantes mixtos, de los que solo algunos cumplieron los criterios de inclusión (p.ej. demencia, DCL), fueron elegibles para inclusión siempre que informaran los resultados por separado para el grupo de interés, o siempre que fue posible obtener dicha información de los autores del ensayo.
Tipos de intervenciones
Intervenciones experimentales
Las intervenciones que cumplieron la definición de EC fueron elegibles para inclusión. Como los términos utilizados para referirse al EC variaron considerablemente, las intervenciones se pueden denominar entrenamiento "cerebral" o "mental", y se pueden describir como "reentrenamiento", "ejercicio", "estimulación", "rehabilitación", "tratamiento", "apoyo", etc.; la definición operativa de las intervenciones elegibles incluyó los siguientes criterios.
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Los participantes se entrenaron en tareas diseñadas dirigidas a uno o más procesos cognitivos, ya sea directa o indirectamente. El entrenamiento adoptó en general la forma de práctica repetida. Los ensayos en los que el objetivo principal fue comparar el desempeño de los participantes que aprendieron cómo cumplir una tarea en diferentes condiciones de aprendizaje (p.ej. sin errores versus errada) en una única sesión (ensayos de entrenamiento único) no fueron elegibles para inclusión.
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Las tareas se completaron en un formato de lápiz y papel o mediante ejercicios computarizados, o fueron análogos estructurados de las tareas diarias en los las bases cognitivas son explícitas y la intervención se dirigió a una capacidad o un proceso cognitivos, en lugar de a una habilidad específica. Se señaló la naturaleza de la intervención (es decir, computarizada o con lápiz y papel o análogos de actividades diarias).
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Las intervenciones se administraron en plataformas comercialmente disponibles o se diseñaron específicamente para el estudio.
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Las intervenciones se podían dirigir a dominios cognitivos únicos o múltiples.
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Era de espera que el nivel de dificultad fuera variado; sin embargo, este aspecto no fue parte de los criterios de inclusión.
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Se excluyeron de esta revisión las intervenciones en las que el EC se combinó con otra intervención experimental diferenciada (p.ej. actividad física, estimulación cerebral), pero lo anterior no se aplicó a los tratamientos estándar, ya que era de esperar que, en general, los participantes se mantuvieran con el tratamiento estándar (generalmente farmacológico).
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EC modificado/alternativo: se reconoció que el EC y otros abordajes terapéuticos dirigidos a la cognición (es decir, estimulación o rehabilitación cognitivas) pueden compartir ciertas características, algunas de los cuales no son posibles de distinguir de una manera directa. Por lo tanto, se incluirán los ensayos de tratamientos complejos dirigidos que también incluyen elementos de estimulación cognitiva (p.ej. orientación), rehabilitación (p.ej. fijación de metas) o psicoeducación (p.ej. uso de estrategias cognitivas), si se determinara por consenso que el EC fue claramente el componente predominante. Cuando fue relevante y lo indicó la heterogeneidad estadística, estas intervenciones se consideraron por separado en análisis de subgrupos.
Intervenciones de comparación
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Lista de espera. En los estudios de este tipo, la intervención experimental se le ofreció al grupo control después de haber concluido el estudio.
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Ningún tratamiento/tratamiento estándar. A menos que se indique lo contrario, cuando los grupos se describieron como "ningún tratamiento" en los estudios individuales, se supuso que la descripción se refería al tratamiento habitual/estándar y no a diferir el tratamiento. El "tratamiento habitual o estándar" se refiere al que normalmente se les proporcionaría en el lugar del estudio a los participantes con demencia leve y podría incluir la provisión de medicación, la atención en el consultorio y el contacto con un equipo de salud mental de la comunidad o la atención diurna, o el apoyo de organizaciones voluntarias, pero no una intervención específica de EC.
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Control activo. Se refiere a las condiciones en las que los participantes se involucraron en alguna forma de actividad, habitualmente durante un número equivalente de sesiones o visitas y recibieron niveles similares de contacto con los investigadores, pero durante las cuales no se ofreció intervención estructurada alguna.
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Tratamientos alternativos. Se refiere a los tratamientos diferentes alternativos que podrían (p.ej. estimulación cognitiva) o no haberse centrado en la cognición (p.ej. actividad física).
Todas las intervenciones
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No se incluyeron las intervenciones administradas en un formato individual o grupal, con o sin participación de los familiares a cargo de la atención.
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No se establecieron restricciones con respecto a los parámetros relacionados con la dosis de la intervención, que incluye la duración general de la intervención o la cantidad de sesiones de tratamiento. Sin embargo, como se describe anteriormente, se excluyeron los tratamientos de sesión única.
Tipos de medida de resultado
Los resultados se consideraron relevantes para esta revisión cuando estuvieron dentro de las siguientes categorías amplias.
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Progresión clínica de la enfermedad.
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Resultados cognitivos.
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Resultados psicosociales para el paciente con demencia.
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Resultados psicosociales para el cuidador primario.
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Resultados substitutos/del mecanismo/de los biomarcadores.
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Resultados económicos.
Aunque se reconoce que los resultados substitutos y los económicos son importantes, se determinó que estaban más allá del alcance de la presente revisión; por lo tanto, el resultado primario principal y los resultados secundarios se seleccionaron a partir de las cuatro categorías principales, como se esboza de manera adicional a continuación.
Resultados primarios
Resultados para el paciente con demencia
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Estado cognitivo global al final del tratamiento (es decir, inmediatamente posintervención). Este resultado se midió al determinar el cambio en las puntuaciones en una medida compuesta de cognición global derivada de todas las medidas cognitivas incluidas en cada ensayo, y los análisis adicionales se centraron en la cognición global, como se refleja en las medidas de cribado de la cognición global (p.ej. MMSE)
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Gravedad de la enfermedad clínica a medio plazo. Este resultado se midió al determinar el cambio en las puntuaciones de las medidas de progresión clínica de la enfermedad (p.ej. la escala Clinical Dementia Rating [CDR], la Dementia Rating Scale [DRS]) en una evaluación de seguimiento realizada entre tres y 12 meses después de la interrupción del tratamiento
Resultados secundarios
Resultados para el paciente con demencia
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Estado cognitivo global a medio plazo. Este resultado se midió al determinar el cambio en las puntuaciones en una medida compuesta de cognición global en la evaluación del seguimiento relevante, y los análisis adicionales se centraron en la cognición global, como se refleja en las medidas de cribado de la cognición global (p.ej. MMSE)
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Gravedad clínica de la enfermedad al final del tratamiento. Este resultado se midió al determinar el cambio en las puntuaciones en las medidas de progresión clínica de la enfermedad (p.ej. CDR, DRS) en la evaluación inmediata postratamiento
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Estado cognitivo específico de dominio al final del tratamiento. Este resultado se midió al determinar el cambio en las puntuaciones en las medidas neuropsicológicas de velocidad de procesamiento, memoria inmediata, memoria retardada, atención y memoria de trabajo, lenguaje (denominación), fluidez de la letra verbal, fluidez de la categoría verbal y función ejecutiva
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Estado cognitivo específico de dominio a medio plazo (tres y 12 meses después de la interrupción del tratamiento). Este resultado se midió al determinar el cambio en las puntuaciones en las medidas neuropsicológicas de velocidad de procesamiento, memoria inmediata, memoria retardada, atención y memoria de trabajo, lenguaje (denominación), fluidez de la letra verbal, fluidez de la categoría verbal y función ejecutiva
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Metacognición (creencias subjetivas con respecto a cognición ‐autoinformada) al final del tratamiento y a medio plazo
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Metacognición (creencias subjetivas con respecto a la cognición ‐ reportada por el informante) al final del tratamiento y a medio plazo
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Estado de ánimo (reflejado en el cambio en las medidas autoinformadas y reportadas por el informante de depresión, ansiedad, etc.) al final del tratamiento y a medio plazo
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Capacidad para las actividades cotidianas al final del tratamiento y a medio plazo
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Síntomas conductuales y psicológicos de la demencia (SCPD) al final del tratamiento y a medio plazo
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Salud general o calidad de vida al final del tratamiento y a medio plazo
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Carga del participante, reflejada en las tasas de retención de los participantes en el ensayo al final del tratamiento
Resultados para el cuidador primario al final del tratamiento
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Estado de ánimo y bienestar (reflejado en el cambio en las medidas autoinformadas de depresión, ansiedad, etc.) al final del tratamiento y a medio plazo
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Carga de la atención al final del tratamiento y a medio plazo
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Calidad de vida al final del tratamiento y a medio plazo
Medidas de resultado
Cuando fue posible se utilizaron los datos de las pruebas publicadas y validadas, los cuestionarios o las técnicas para la evaluación de un resultado determinado. En los casos en los que un resultado se evaluó con una medida no publicada o no establecida, se hizo todo lo posible para obtener la información acerca de las propiedades estadísticas de la prueba o la escala en cuestión, antes de determinar si se aceptaba la medida. Cuando fue posible, las medidas cognitivas para dominios cognitivos específicos se clasificaron según los textos oficiales establecidos (Spreen 1998), y, cuando fue necesario, mediante consenso entre los autores del estudio.
Evaluación del resultado
Los ensayos se incluyeron si se registró, como mínimo, una evaluación inicial y una evaluación postratamiento.
Métodos de búsqueda para la identificación de los estudios
Búsquedas electrónicas
We searched ALOIS (www.medicine.ox.ac.uk/alois), the Specialised Register of the Cochrane Dementia and Cognitive Improvement Group (CDCIG), on 5 July 2018.
ALOIS, which is maintained by the Information Specialists for CDCIG, contains studies that fall within the areas of dementia prevention, dementia treatment and management, and cognitive enhancement in healthy elderly populations. These studies are identified by:
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searching several major healthcare databases: MEDLINE, Embase, Cumulative Index to Nursing and Allied Health Literature (CINAHL), and PsycINFO;
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searching several trial registers: ClinicalTrials.gov and the International Clinical Trials Register Platform (ICTRP) of the World Health Organization (WHO), which includes International Standard Randomized Controlled Trials Number (ISRCTN); the Chinese Clinical Trials Register; the German Clinical Trials Register; the Iranian Registry of Clinical Trials; and the Netherlands National Trials Register, plus others;
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searching the Central Register of Controlled Trials, in the Cochrane Library (CENTRAL); and
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searching grey literature sources: Institute for Scientific Information (ISI) Web of Science Core Collection.
To view a list of all sources searched for ALOIS, please visit the ALOIS website (www.medicine.ox.ac.uk/alois).
Details of the search strategies run in healthcare bibliographic databases, used for retrieval of reports of dementia, cognitive improvement, and cognitive enhancement trials, can be viewed on the website of the Cochrane Dementia and Cognitive Improvement Group at http://dementia.cochrane.org/searches.
We ran additional searches in MEDLINE, Embase, PsycINFO, CINAHL, Latin American Caribbean Health Sciences Literature (LILACS), ClinicalTrials.gov, and the WHO Portal/ICTRP, to ensure that searches for this review were as comprehensive and as up‐to‐date as possible. Search strategies used and the number of hits retrieved can be seen in Appendix 1.
Búsqueda de otros recursos
We screened reference lists from included trials, as well as reference lists of recent systematic reviews, and relevant recent guidelines. We contacted experts in the field to request additional randomised trial reports not identified by the search.
Obtención y análisis de los datos
Selección de los estudios
One review author (AM) reviewed titles and abstracts from the complete de‐duplicated list of search results, and we split the records for an independent screening by two additional review authors (ABF, AG), to identify all potentially relevant RCTs of CT for people with dementia and to remove obviously irrelevant studies. Whenever there was doubt regarding the eligibility of a trial, we selected it for full review of the methods. Following the initial screening, we applied the same approach for evaluation of full methods from short‐listed articles. We identified and merged multiple reports from the same study, and we contacted study authors to clarify issues related to the eligibility of a trial for inclusion. We settled discrepancies in the classification of trials through discussion between two review authors and ruling of a senior review author who is a content area expert (LC). The study selection process was unblinded.
Extracción y manejo de los datos
JS extracted data from study reports onto a standardised, structured data entry form under supervision of the lead review author (ABF), who also independently extracted data for variables requiring some judgement (e.g. intervention integrity/fidelity), and we subsequently entered the data into Review Manager 5 software (Review Manager 5). We sought additional information from study authors as appropriate. Data extracted from each trial included detailed characteristics of trials (e.g. settings, outcomes), design features (e.g. delivery format, blinding), participant characteristics (e.g. diagnoses, age, gender, education, medications), and elements of experimental and control interventions (e.g. intensity, frequency, duration, key intervention features). We also extracted information about additional variables of interest for the investigation of effect moderators, including registration status, sources of funding, conflicts of interest, adherence and retention, type of control, whether intervention integrity/fidelity was addressed, and adverse events. For each outcome of interest, we extracted mean scores and standard deviations on relevant measures from all available evaluations.
Evaluación del riesgo de sesgo de los estudios incluidos
Pairs of review authors independently conducted assessment of risk of bias using Cochrane's 'Risk of bias' tool (Higgins 2017). We resolved disagreements by discussion with a third review author who is a subject matter expert (LC). Consistent with Cochrane's 'Risk of bias' tool, we assessed bias in the following domains: sequence generation, allocation concealment, blinding of participants and investigators, incomplete outcome data, and selective reporting of outcomes. We rated studies as 'low risk', 'high risk', or 'unclear risk' in each of these domains.
Medidas del efecto del tratamiento
We generally calculated effect estimates in primary trials along with their 95% confidence intervals (CIs) using change‐from‐baseline scores. Calculations of the standard deviation of change scores were based on the assumption that the correlation between measurements at baseline and those at subsequent time points is r = 0.8, in keeping with other relevant reviews (e.g. Lampit 2014). However, for consistency with previous versions of this review, we also conducted sensitivity analyses of the primary outcome with a conservative r = 0 assumption, which overestimates the standard deviation of the change. We treated outcome measures as measured on a continuous scale. In some cases, we derived outcomes from ordinal rating scales; provided these contained a reasonably large number of categories (more than 10), we treated data as continuous variables arising from a normal distribution. For dichotomous outcomes (e.g. participant retention), we expressed effects as risk ratios (RRs) along with 95% CIs.
Cuestiones relativas a la unidad de análisis
We expected four types of unit of analysis issues: cross‐over trial designs, multiple‐armed trials (more than one treatment/control condition), repeated assessments, and availability of multiple measures of the same outcome in primary trials. Our approach to the management of these issues was as follows.
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Cross‐over trials: we used only data from the first treatment period (before cross‐over).
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Multiple conditions:
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experimental conditions: in trials that include at least three conditions, assuming that at least one condition satisfies our definition of a comparison condition (see above), we combined data from all conditions that we judged to fit our definition of CT into a single group using a relevant formula (Higgins 2017). We excluded from this review trials that include two relevant experimental conditions but no eligible control condition; and
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control conditions: we combined data from two control conditions of the same broad type (i.e. no treatment). In the event that a trial included different types of control comparisons that are not alternative treatments (e.g. it included both no treatment and active control groups), we used in the analysis data from both these control conditions by splitting the sample size of the experimental condition into two separate groups, according to the procedure described in Chapter 7 of the Cochrane Handbook for Systematic Reviews of Interventions (Higgins 2017).
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Repeated post‐intervention assessments: we conducted separate comparisons to assess primary and secondary outcomes at end of treatment (i.e. immediately post intervention), and in the short to medium term (up to 12 months post intervention). Within this follow‐up period, we used in the analysis data from the last available assessment. We did not use data from follow‐up assessments conducted more than 12 months following the end of treatment assessment.
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Multiple measures of the same outcome: in primary trials in which multiple measures of the same outcome were used, the following principles guided the selection of measures for data extraction:
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general principles: we used a composite outcome measure if one was derived by the study authors. If no composite was available, we generally used data from a test that matched the most commonly used measure in other studies that contributed data to the particular outcome. Established/published measures of the outcome were preferred over measures developed for the specific study. If more than one established measure of an outcome was used, and no measure was identified that was used by most trials contributing to the specific outcome, we created a simple composite score from standardised scores on the different measures and used it in the analysis;
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cognitive outcomes: for each trial, we computed a global composite cognitive score by calculating a standardised change‐from‐baseline score for each measure (change score divided by the standard deviation of the change score), and deriving a simple mean and standard deviation of the z‐scores associated with all cognitive measures from a trial. In addition, for evaluation of domain‐specific cognitive scores, we used the following principles:
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Psychomotor information processing speed: we preferred visuospatial measures where available.
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Attention, immediate and delayed memory: we preferred auditory‐verbal measures for evaluation of attention and immediate and delayed memory. We preferred tasks that involve the learning of information over several trials (i.e. word lists) over tasks in which the information is presented only once (e.g. story or figure recall). We preferred measures of free recall over measures of cued/recognition where available.
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Executive functions: we preferred tasks that reflect planning, organisation, decision‐making, regulation of performance, and set‐shifting aspects of executive functions over tasks that are more strongly associated with volition or purposive action aspects of executive functions (Lezak 2004). In the event that several measures of executive function were used in a study, we computed a composite executive function score by taking the mean of standardised scores for each of these measures.
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Meta‐cognitive outcomes: we generally preferred self‐reported measures of contentment/satisfaction with one's cognitive ability over informant‐reported measures;
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Mood outcomes: we generally preferred measures of depression over measures of anxiety or apathy, and self‐reported measures over informant‐reported measures; and
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Activities of daily living (ADLs): we preferred measures of instrumental ADLs over measures of basic ADLs, and informant‐reported measures over self‐reported measures. This is based on the finding that self‐ and informant‐reported daily functions show significant discrepancy in people with dementia, and that informant reports of daily function are more closely associated with actual memory performance (Farias 2005).
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Manejo de los datos faltantes
We extracted the number of participants who commenced and completed the intervention in each condition, and this contributed to our assessment of risk of bias due to incomplete outcome data. Wherever possible, we contacted trial authors in an effort to obtain relevant unreported data. In general, we assumed that data were missing at random, and that analyses in individual studies were generally performed on a per‐protocol (PP) rather than on an intention‐to‐treat (ITT) basis. When a trial report included relevant data from both ITT and PP samples, we generally used the PP data for consistency with most of the trials. We evaluated the impact of missing data on pooled effect estimates by performing sensitivity analyses (see below).
Evaluación de la heterogeneidad
In addition to a visual inspection of the forest plots, we assessed statistical heterogeneity using a standard Chi² statistic and the associated l² statistic. Consistent with recommendations (Deeks 2017), we deemed heterogeneity to be present when the Chi² statistic is significant at the P = 0.1 level, or when l² suggests that more than 40% of the variability in the effect estimate is due to heterogeneity. Where substantial heterogeneity was detected, we explored the sources of heterogeneity by conducting subgroup analyses (see below).
Evaluación de los sesgos de notificación
For primary outcomes, we first evaluated the presence of reporting bias through visual examination of funnel plots for small‐study effects. We examined the significance of any apparent asymmetry by using Egger's test (Egger 1997), and by providing follow‐up with the 'trim and fill' test (Duval 2000), if asymmetry of the plot was confirmed.
Síntesis de los datos
We performed data synthesis using Review Manager 5 software. In relation to each of the main outcomes of interest, we undertook the following separate comparisons.
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CT versus control (no/standard treatment/wait‐list or active control) at end of treatment (i.e. immediately post intervention).
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CT versus control (no/standard treatment/wait‐list or active control) in the medium term (3 to 12 months following end of treatment).
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CT versus alternative treatment at end of treatment (i.e. immediately post intervention).
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CT versus alternative treatment in the medium term (3 to 12 months following end of treatment).
Within each of the planned comparisons, we pooled data in relation to each outcome of interest when data from at least two trials were available.
We performed inverse‐variance, random‐effects meta‐analyses for all outcomes. We used mean differences (MDs) with 95% CIs whenever studies used the same outcome measure, whereas we used standardised mean differences (SMDs), which show the absolute mean difference divided by the pooled standard deviation, when the same outcome was assessed by different measures.
Análisis de subgrupos e investigación de la heterogeneidad
In relation to each outcome, we carried out subgroup analyses to evaluate the potential impact of categorical treatment modifiers. We carried out subgroup analyses only when statistical heterogeneity was suggested by the relevant statistics (I² ≥ 40%) (Deeks 2017), and when at least three studies were available for each subgroup. We examined the following categorical effect modifiers.
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Type of intervention 1: 'straight' CT versus 'augmented' CT ‐ in which CT was combined with elements of cognitive rehabilitation or cognitive stimulation (or both).
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Type of intervention 2: multi‐domain CT versus single‐domain CT (e.g. working memory).
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Intervention dose: more intense (i.e. more than three formal sessions per week) versus less intense interventions (i.e. up to three formal sessions per week).
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Intervention duration: longer interventions (i.e. more than three months) versus shorter interventions (i.e. three months or less).
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Follow‐up period: we compared studies with follow‐up in the short term (up to three months after treatment cessation) versus trials that included longer‐term follow‐up (up to 12 months after treatment cessation).
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Risk of bias: studies with high risk of bias in at least two critical domains versus other studies with lower risk of bias. For the purposes of these analyses, critical domains were sequence generation, blinding of outcome assessment, incomplete data, and selective reporting. Although we acknowledge that allocation concealment is increasingly regarded as a critical domain, this remains a relatively infrequent practice in these types of studies.
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Funding source: trials funded by commercial entities versus those based on competitive funding.
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Registration: registration status of the trial (prospective/retrospective vs not registered/not reported).
Análisis de sensibilidad
To determine whether findings for the primary outcomes were affected by assumptions made regarding strength of the correlation between scores before and after the interventions, we repeated analyses of the primary outcomes after applying the zero correlation assumption, which overestimates the standard deviation of change scores. We repeated evaluation of primary outcomes by performing a further sensitivity analysis using post‐intervention scores only, thus avoiding the need to estimate the standard deviation of change scores.
GRADE and 'Summary of findings' tables
We expressed our overall confidence in the evidence for each outcome using GRADE, and we presented this in 'Summary of findings' tables and in the review text. We described the quality of evidence as 'high', 'moderate', 'low', or 'very low', using the GRADE framework, which we applied to all primary and secondary outcomes in each comparison. In relation to each outcome, we considered certainly in the estimates in relation to risk of bias, indirectness, inconsistency, imprecision, and publication bias for studies contributing data to estimation of the outcome. Two review authors (ABF and JS) worked together to grade the evidence. We considered estimates based on data from a single study against the same parameters, with the exception of inconsistency and publication bias dimensions. In relation to risk of bias, we generally downgraded by 1 point, reflecting serious concern, when sensitivity analysis in which we removed studies classified as at overall 'high risk' led to a difference in the estimate of effect of between 0.2 standard deviation (SD) and 0.3 SD. We downgraded by 2 points, reflecting very serious concern, when sensitivity analysis led to a difference in the estimate of effect that was greater than 0.3 SD. We generally downgraded by 1 point for serious concerns regarding inconsistency when moderate heterogeneity was observed (40% < l² < 75%) and when subgroup analyses (when relevant; see below) did not seem to explain heterogeneity in the estimates. We generally downgraded by 2 points when high heterogeneity (l² > 75%) was observed and when subgroup analyses (when relevant) did not seem to explain the heterogeneity. Concerning imprecision, following the rule of thumb in the GRADE Handbook, we downgraded by 1 point when the sample size on which the estimate was based was smaller than 400 participants, or in the event that the confidence interval of the estimate included both a potentially important effect and a clinically unimportant effect (defined as an effect smaller than 0.2 in either direction for continuous outcomes). We downgraded by 2 points when the estimate was based on fewer than 400 participants (for continuous outcomes), and when the CI of the estimate included both a potentially important effect and no effect, or in the event that the CI included all relevant possibilities (positive effect, no effect, and effect in the opposite direction), irrespective of the sample size. Regarding publication bias, we indicated that it was 'strongly suspected' in cases where on visual inspection, asymmetry in the funnel plot for a relevant outcome was reasonably evident. We did not conduct formal tests of asymmetry, and we inspected funnel plots only when at least 10 studies contributed to the outcome. Hence, we could not evaluate this for many outcomes, including all outcomes in the comparison between cognitive training and use of an alternative treatment. Finally, we generally regarded the correspondence between findings in relation to various outcomes and the review question as specified in the PICO to be adequate, so we decided not to downgrade the evidence on the basis of indirectness.
We generated 'Summary of findings' tables using GRADEpro GDT software (GRADEpro GDT), and we imported these into the review. Summary of findings table 1, Summary of findings table 2, Summary of findings table 3, and Summary of findings table 4 include the following primary and secondary outcomes.
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Global cognition at end of intervention.
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Clinical disease severity at latest follow‐up, up to 12 months following treatment cessation.
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Delayed memory ability at end of intervention.
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Capacity to perform activities of daily living.
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Mood and well‐being of participant.
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Mood and well‐being of informant/caregiver.
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Treatment burden (retention rates).
Results
Description of studies
Results of the search
The flow of studies through the search and screening process can be seen in Figure 1 (review flow chart). After de‐duplication, 1166 records underwent full title and abstract review, on the basis of which we deemed 157 titles to be potentially relevant; we then reviewed the full text of these studies (when available) to confirm eligibility. The full‐text review revealed that 33 studies met our inclusion criteria and 32 studies contributed data for at least one meta‐analysis. Of these, 10 studies were included in a previous Cochrane Review on CT and rehabilitation for people with mild to moderate dementia (Bahar‐Fuchs 2013).
Study flow diagram.
Included studies
Pertinent details of the included studies, extracted from the published manuscript and, where noted, provided by study authors, are presented in the Characteristics of included studies table. Further details concerning the characteristics of participants in included studies are presented in Table 1, and details concerning dose and duration of the interventions are shown in Table 2. The 33 studies selected for inclusion in the current review were published between 1988 and 2018. With the exception of Davis 2001 and Barban 2016, which did not use a cross‐over design, all trials were parallel‐group RCTs. Amieva 2016, Barban 2016, Beck 1988, Jelcic 2014, Kallio 2018, Kao 2016, Lee 2013, and Tsantali 2017 were described as multi‐site trials; all others were assumed to be single‐site trials. Only three of the included trials made reference to registration in a public trial registry; Brueggen 2017 and Kallio 2018 were prospectively registered, whereas Kao 2016 was retrospectively registered. We assumed that all other trials were unregistered. The included trials were conducted in 12 countries, with six conducted in the USA (Beck 1988; Cahn‐Weiner 2003; Davis 2001; Koltai 2001; Quayhagen 1995; Quayhagen 2000), two in Germany (Brueggen 2017; Heiss 1993), 12 in Italy (Bergamaschi 2013; Cavallo 2016; de Vreese 1998; Galante 2007; Giovagnoli 2017; Giuli 2016; Jelcic 2012; Jelcic 2014; Mapelli 2013; Serino 2017; Trebbastoni 2018; Venturelli 2016 ), one in Sweden (Neely 2009), one in Japan (Kawashima 2005), three in France (Amieva 2016; Boller 2011; Goudour 2011), two in Spain (Fernández‐Calvo 2011; Quintana Hernandez 2014), two in China (Kao 2016; Lee 2013), one in Korea (Kim 2015), one in Greece (Tsantali 2017), and one in Finland (Kallio 2018). Barban 2016 was a multi‐country trial with recruitment in Italy, Greece, Norway, and Spain. It is worth noting that approximately one‐third of all included studies (13) were conducted in Italy, 10 of these in the past six years. We further note that no eligible trials were found from the UK, Canada, or Australia, and that no eligible studies were found that were conducted in the USA since 2003 (these studies were all included in a previous review ‐ Bahar‐Fuchs 2013). Samples in the included studies ranged from 12 participants in Galante 2007 to 653 participants in Amieva 2016, and 13 of the included studies had samples of more than 50 participants. Of the 33 included studies, 30 were published in English, two in Spanish, and one in French. A member of the review team (JS) translated essential information from Spanish and French studies to English.
| Study | Condition | Sample size (at baseline) | Age, mean (SD), range | Gender balance (m:f) | Education | Medications (number or proportion on dementia‐related medication) | Baseline MMSE score | Retention rates | Adverse reactions |
| Cognitive training | 10 | 74 (range 68 to 75) | 5:5 | Attended college = 2 | None | Not reported | 100% | "many subjects complained of tiring" | |
| Control | 10 | 76 (range 70 to 93) | 3:7 | Attended college = 1 | None | Not reported | 100% | Not specified | |
| Cognitive training | Not reported (18 completed the study) | 65.9 (6.28) | 9:9 | Not reported | None | 20.55 (4.42) | Not reported | Not specified | |
| Control (social support) | Not reported (17 completed the study) | 66.63 (10.17) | 10:7 | Not reported | None | 20.23 (4.10) | Not reported | Not specified | |
| Control (CT+pyritinol) | 17 | 67.18 (8.51) | Not reported | 88.88 | Not reported | 21.64 (4.55) | Not reported | Not specified | |
| Control (CT+phosphatidylserine) | 18 | 66.74 (6.93) | Not reported | 125 | Not reported | 20.88 (4.73) | Not reported | Not specified | |
| Cognitive training | 25 | Not reported | Not reported | Not reported | Not reported | 109.8 (12.0) DRS | Not reported | Not specified | |
| Passive control | 25 | Not reported | Not reported | Not reported | Not reported | 109.2 (11.7) DRS | Not reported | Not specified | |
| Active control | 28 | Not reported | not reported | Not reported | Not reported | 110 (12.2) DRS | Not reported | Not specified | |
| Cognitive training | 12 | NA | NA | NA | NA | NA | NA | NA | |
| Cognitive training+AChE‐I | 12 | Not reported | Not reported | Not reported | All | 17.33 (3.39) | 100% | Not specified | |
| Control (placebo drug) | 12 | Not reported | Not reported | Not reported | All | 17.44 (4.67) | 100% | Not specified | |
| Control (AChE‐I) | 12 | Not reported | Not reported | Not reported | All | 17 (3.20) | 100% | Not specified | |
| Cognitive training | 21 | Not reported | Not reported | Not reported | Not reported | Not assessed | Not reported | Not specified | |
| Passive control | 15 | Not reported | Not reported | Not reported | Not reported | Not assessed | Not reported | Not specified | |
| Dyadic counselling control | 29 | Not reported | Not reported | Not reported | Not reported | Not assessed | Not reported | Not specified | |
| Seminar groups control | 22 | Not reported | Not reported | Not reported | Not reported | Not assessed | Not reported | Not specified | |
| Early‐stage daycare control | 16 | Not reported | Not reported | Not reported | Not reported | Not assessed | Not reported | Not specified | |
| Cognitive training | 19 | 68.67 (3.86) | 10:9 | 15.06 (3.86) | 5 | 21.84 (4.03) | 100% | Not specified | |
| Control | 18 | 72.56 (7.62) | 6:12 | 12.97 (2.56) | 4 | 22.78 (4.45) | 100% | Not specified | |
| Cognitive training (group and individual) ‐ shared data | 16 | 72.9 (6.7) | Not reported | 15.0 (4.0) | Not reported | 22.9 (3.6) | 87.5% (missed: 2 participants from group CT) | Not specified | |
| Control | 8 | 73.9 (7.2) | Not reported | 15.0 (4.0) | Not reported | 26.6 (2.5) | 100% | Not specified | |
| Cognitive training | 19 | 77. 8 (6.9) | 9:8 | 12.7 (2.1) | All participants: donepezil | 24.3 (2.2) | 89.4% (missed: 3 participants) | Not specified | |
| Control | 20 | 76.0 (7.7) | 5:12 | 13.1 (3.5) | All participants: donepezil | 25.1 (1.7) | 85% (missed: 3 participants) | Not specified | |
| Cognitive training | 7 | Not reported | Not reported | Not reported | All | 22.9 (3.1) | 100% | Not specified | |
| Control | 5 | Not reported | Not reported | Not reported | All | 23.1 (1.8) | 80% (missed: 1 participant) | Not specified | |
| Cognitive training | 10 | 74.8 (6.7) | 6:4 | Not reported | Not reported | 22.9 (4.15) | 100% | Not specified | |
| Control | 10 | 77.0 (6.6) | 6:4 | Not reported | Not reported | 18.6 (5.7) | 90% (missed: 1 participant) | Not specified | |
| Cognitive training | 16 | 85.1 (5.4) (range 76 to 96) | Not reported | Not reported | Not reported | 19.9 (7.0) | 100% | Not specified | |
| Control | 16 | 86.3 (4.9) (range 78 to 96) | Not reported | Not reported | Not reported | 19.6 (5.4) | Not reported | Not specified | |
| Cognitive training (recollection) | 12 | 81.58 | 4:8 | 10.92 (2.94) | Not reported | 24 (3.05) | Not reported | Not specified | |
| Cognitive training (recognition) | 12 | 82.67 | 4:8 | 12.08 (2.07) | Not reported | 24.83 (2.12) | Not reported | Not specified | |
| Control | 12 | 79.33 (3.85) | 5:7 | 11.08 (3.85) | Not reported | 25.83 (1.40) | Not reported | Not specified | |
| Cognitive training (BBA) | 15 | 75.80 (4.27) | 9:6 | 7.46 (1.84) | All participants on IaCHe | 19.33 (2.48) | Not reported | Not specified | |
| Cognitive training (IPP) | 15 | 75.60 (4.55) | 8:7 | 8.40 (2.77) | All participants on IaCHe | 20 (2.92) | Not reported | Not specified | |
| Control | 15 | 75.86 (4.15) | 8:7 | 7.26 (3.34) | All participants on IaCHe | 20.44 (1.90) | Not reported | Not specified | |
| Cognitive training | 5 | 68.8 (10.0) | 2:3 | 9.0 (1.2) | Not reported | 20.2 (2.8) | Not reported | Not specified | |
| Control | 5 | 70.0 (5.9) | 2:3 | 9.6 (1.9) | Not reported | 20.6 (4.1) | Not reported | Not specified | |
| Cognitive training | 20 | 82.9 (3.6) | 2:18 | 6.7 (2.9) | Not reported | 24.4 (2.8) | 100% | Not specified | |
| Control | 20 | 81.8 (5.5) | 5:15 | 8.25 (3.6) | Not reported | 25 (2.6) | 100% | Not specified | |
| Cognitive training | 16 | 78.19 (5.50) | Not reported | 7.25 (3.24) | All participants: donepezil 5 or 10 mg/d | 20.25 (2.95) | Not reported | Not specified | |
| Control | 16 | 77.72 (5.06) | Not reported | 5.61 (2.30) | All participants: donepezil 5 or 10 mg/d | 21.94 (2.01) | Not reported | Not specified | |
| Cognitive training (CELP) | 6 | Not reported | 1:6 | Nil: 42.8% | Not reported | 15.3 (2.7) | Not reported | Not specified | |
| Cognitive training (TELP) | 6 | Not reported | 3:3 | Nil: 16.7% | Not reported | 17.6 (4.7) | Not reported | Not specified | |
| Control | 7 | Reported | 2:4 | Nil: 33.3% | Not reported | 17 (3.5) | Not reported | Not specified | |
| Cognitive training | 10 | 82.6 (4.85) | Not reported | 4.6 (1.5) | Not reported | 20.1 (4.2) | 100% | Not specified | |
| Control (occupational therapy) | 10 | 84.5 (5.06) | Not reported | 4.3 (1.82) | Not reported | 19.7 (3.8) | 100% | Not specified | |
| Control (no treatment) | 10 | 84.7 (4.42) | Not reported | 4 (1.15) | Not reported | 18.8 (2.68) | 100% | Not specified | |
| Cognitve training (LSS‐tele) | 7 | 86 (5.1) | 2:5 | 6 (3.5) | Not reported | 23.7 (2.8) | Not reported | Not specified | |
| Cognitive training (LSS‐direct) | 10 | 82.7 (6) | 3:7 | 6.7 (3.3) | Not reported | 24.9 (2.5) | Not reported | Not specified | |
| Control | 10 | 82.3 (5.9) | 1:9 | 8.7 (3.7) | Not reported | 24.8 (2.7) | Not reported | Not specified | |
| Cognitive training | 32 | Not reported | Not reported | Not reported | 100% donepezil | Not reported | 84.3% | Not specified | |
| Control muscular relaxation | 34 | Not reported | Not reported | Not reported | 100% donepezil | Not reported | 97% | Not specified | |
| Control mindfulness | 36 | Not reported | Not reported | Not reported | 100% donepezil | Not reported | 97.2% | Not specified | |
| Control | 25 | Not reported | Not reported | Not reported | 100% donepezil | Not reported | 100% | Not specified | |
| Cognitive training | 22 | 70.4 (7.9) | 8:14 | 8.7 (3.8) | Not reported | 23.1 (2.1) | 100% | Not specified | |
| Control | 21 | 71.4 (8.2) | 7:14 | 8.5 (3.1) | Not reported | 22.8 (1.8) | 100% | Not specified | |
| Cognitive training | 170 | 78.5 (7.2) | 69:99 (data from 168 participants) | No diploma: 10% | 89.4% IaCHe, memantine | 21.5 (3.2) | 72.94% (missed: 46 participants) | Not specified | |
| Usual care | 154 | 78.7 (6.5) | 63:90 (data from 154 participants) | No diploma: 15.6% | 86.4% IaCHe, memantine | 21.6 (3.3) | 70.78% (missed: 45 participants) | Not specified | |
| Reminiscence therapy | 172 | 78.8 (6.9) | 61:108 (data from 169 participants) | No diploma: 16.3% | 90.1% IaCHe, memantine | 21.1 (3.1) | 68.60% (missed: 54 participants) | Not specified | |
| Individualised cognitive rehabilitation | 157 | 78.9 (6.2) | 64:92 (data from 172 participants) | No diploma: 17.2% | 86.6% IaCHe, memantine | 21.6 (3.0) | 77.07% (missed: 36 participants) | Not specified | |
| Cognitive training | 40 | 76.5 (2.88) | 13:27 | 8.53 (3) | 36/40 | 22.65 (1.74) | 100% | Not specified | |
| Control | 40 | 76,33 (3,83) | 16:24 | 8.12 (2.79) | 38/40 | 23.05 (2.44) | 100% | Not specified | |
| Cognitive training (spaced retrieval) | 48 | 83.10 (5.0) | 33:13 | Illiterate: 14 (30, 4) | Not reported | 12.33 (5.41) | 95.83% (missed: 2 participants) | Not specified | |
| Cognitive training (spaced retrieval+Montessori activities) | 52 | 82.69 (6.81) | 37:12 | Illiterate: 9 (18, 4) | Not reported | 12.08 (4.05) | 94.23% (missed: 3 participants) | Not specified | |
| Control | 48 | 81.82 (5.89) | Male 29 (64, 4) | Illiterate: 13 (28, 9) | Not reported | 11.84 (5.49) | 93.75% (missed: 3 participants) | Not specified | |
| Cognitive training | 42 | 76.5 (5.7) | 13:29 | 8.8 (3.6) | Not reported | 23.4 (1.9) | 94.79% (from the 3 groups, not only PWD) | Not specified | |
| Control | 39 | 76.9 (5.7) | 11:28 | 9.2 (3.7) | Not reported | 23.4 (1.7) | 89.14% (from the 3 groups, not only PWD) | Not specified | |
| Cognitive training | 51 | 76.5 (4.3) | 40:60 | 5.9 (4.1) | Not reported | 20.2 (3.7) | 94.11% (missed: 3 participants) | Not specified | |
| Control | 50 | 78.7 (5.9) | 28:72 | 4.5 (2.3) | Not reported | 20.3 (3.5) | 94% retention (missed: 3 participants) | Not specified | |
| Cognitive training | 20 | 86 (9) | 5:15 | Not reported | No anti‐dementia drugs reported | 14.0 (1.6) | 100% | Not specified | |
| Aerobic exercise | 20 | 84 (7) | 4:16 | Not reported | No anti‐dementia drugs reported | 13.7 (2.3) | 100% | Not specified | |
| Aerobic exercise+Cognitive training | 20 | 85 (8) | 6:14 | Not reported | No anti‐dementia drugs reported | 13.8 (1.5) | 100% | Not specified | |
| Control | 20 | 84 (10) | 17:13 | Not reported | No anti‐dementia drugs reported | 14.2 (1.5) | 100% | Not specified | |
| Cognitive training | 17 | 73.4 (5.7) | Not reported | 9.9 (4.2) | All were on inhibitors of cholinesterase, used for at least 2 years | 23.2 (1.6) | 100% | Not specified | |
| Alternative treatment (cognitive stimulation) | 21 | 74.2 (5.6) | Not reported | 9.5 (4.1) | All were on inhibitors of cholinesterase, used for at least 2 years | 23.1 (1.4) | 100% | Not specified | |
| Control | 17 | 73.3 (4.9) | Not reported | 9.8 (4.0) | All were on inhibitors of cholinesterase, used for at least 2 years | 22.5 (0.9) | 100% | Not specified | |
| Cognitive training | 8 | (53 to 80) | 4:4 | (10 to 17) | 5 participants on anti‐dementia medication | 24 (3.55) | 100% | Not specified | |
| Control | 10 | (59 to 83) | 5:3 | (11 to 17) | All 8 participants were on anti‐dementia medication | 21.75 (3.24) | 80% (missed: 2 participants) | Not specified | |
| VR group ‐ AD | 10 | 86.60 | 1:9 | 9.80 (3.97) | Not reported | 22.05 (1.62) | 100% | Not specified | |
| VR group ‐ normal ageing | 8 | 86.62 (6.19) | 4:4 | 9.12 (5.05) | Not reported | 27.73 (2.02) | 100% | Not specified | |
| Control | 10 | 88.70 (3.59) | 2:8 | 7.00 (5.00) | Not reported | 20.79 (1.80) | 100% | Not specified | |
| Cognitive training | 13 | 71.69 (7.88) | 3:10 | 6.92 (2.46) | Not reported | 23.62 (1.94) | 100% (4 dropped out before treatment) | No adverse effects | |
| Alternative treatment (music therapy) | 13 | 73.92 (7.74) | 7:6 | 10.46 (5.3) | Not reported | 22.85 (6.28) | 100% (4 dropped out before treatment) | No adverse effects | |
| Alternative treatment (neuroeducation) | 13 | 75.31 (5.56) | 8:5 | 7.31 (4.01) | Not reported | 21.15 (3.48) | 100% (3 dropped out before treatment) | No adverse effects | |
| Cognitive training | 54 | 74.26 (6.97) | 28:26 | 8.64 (4.21) | 78% AChEIs | 22.20 (2.37) | 88.80% (missed: 6 participants) | 2 falls (group is not reported) and 2 deaths (1 from each group). Study authors stated that these events were not related to any of the experimental procedures performed | |
| Control | 86 | 76.01 (6.46) | 34:52 | 8.40 (4.12) | 88% AChEIs, | 22.89 (2.72) | 100% | 2 falls (group is not reported) and 2 deaths (1 from each group). Study authors stated that these events were not related to any of the experimental procedures performed | |
| Cognitive training | 76 | 82.6 (5.5) | 34.2% male | 32 < 8 years | 60 (78.9%) taking AD medications; 33 (43.4%) taking anticholinergics | 21.0 (4.3) | 68 of 76 | Not specified | |
|
| Control | 71 | 83.6 (5.4) | 21.1% male | 36 < 8 years | 62 (87.4%) taking AD medications; 37 (52.1%) taking anticholinergics | 19.9 (3.9) | 49 of 71 | Not specified |
Date in the table, in some cases, are reported only for those participants who completed the interventions.
AChEI: anti‐cholinesterase inhibitor.
AD: Alzheimer's disease.
BBA: Big Brain Academy.
CELP: computerised errorless learning‐based memory training programme.
CT: cognitive traininng.
IPP: Integrated Psychostimulation Program.
LSS: lexical‐semantic simulation.
TELP: therapist‐led errorless programme.
VR: virtual reality.
| Study | Duration (weeks) | Session frequency (per week) | Total number of sessions | Session duration (minutes) | Total direct intervention (minutes) | Total direct intervention (hours) | Session format | Adherence rates | Fidelity measures |
| 6 (cognitive training) | 3 | 18 | Approx. 35 | Approx. 630 | Approx. 10.5 | Individual, with a research assistant | Not reported | Not reported | |
| NA (control) | NA | NA | NA | NA | NA | NA | NA | NA | |
| 24 (cognitive training) | 2 | 48 | 60 | 2880 | 48 | Individual | Not reported | Not reported | |
| 24 (social support) | 1 | 24 | 60 | 1440 | 24 | Individual | Not reported | Not reported | |
| 24 (cognitive training+pyritinol) | 2 | 48 | 60 | 2880 | 48 | Individual | Not reported | Not reported | |
| 24 (cognitive training+phosphatidylserine) | 2 | 48 | 60 | 2880 | 48 | Individual | Not reported | Not reported | |
| 12 (cognitive training) | 6 | 72 | 60 | 4320 | 72 | Individual | Not reported | Caregiver and care recipient were trained together in programme implementation techniques. Return demonstrations by caregivers were required to validate training | |
| NA (passive control) | NA | NA | NA | NA | NA | NA | NA | NA | |
| 12 (active control) | Not reported | Not reported | Not reported | Not reported | Not reported | Not reported | Not reported | Caregiver and care recipient were trained together in programme implementation techniques. Return demonstrations by caregivers were required to validate training | |
| NA (cognitive training) | NA | NA | NA | NA | NA | NA | NA | NA | |
| 12 (cognitive training+ChE‐I, after 12 weeks on drug) | 2 | 24 | 45 | 1080 | 18 | Individual | Not reported | Not reported | |
| 12 (placebo drug) | NA | NA | NA | NA | NA | NA | Not reported | Not reported | |
| 12 (AChE‐I, after 12 weeks on drug) | NA | NA | NA | NA | NA | NA | Not reported | Not reported | |
| 8 (cognitive training) | 1 | 8 | 90 | 720 | 12 | Individual, with help from caregiver | Not reported | Ongoing monitoring of personnel performance to ensure uniformity and consistency of administration of assessments or interventions | |
| 8 (dyadic counselling) | 1 | 8 | 90 | 720 | 12 | Dyad | Not reported | Ongoing monitoring of personnel performance to ensure uniformity and consistency of administration of assessments or interventions | |
| 8 (seminar groups) | 1 | 8 | 90 | 720 | 12 | Group | Not reported | Ongoing monitoring of personnel performance to ensure uniformity and consistency of administration of assessments or interventions | |
| 8 (daycare) | 7 | 8 | 240 | 1920 | 32 | Group | Not reported | Ongoing monitoring of personnel performance to ensure uniformity and consistency of administration of assessments or interventions | |
| NA (wait‐list control) | NA | NA | NA | NA | NA | NA | NA | NA | |
| 5 (cognitive training) | 1 | 5 | 60 | 300 | 5 | Individual | Not reported | Not reported | |
| 5 (control) | 1 | 5 | 60 | 300 | 5 | Individual | Not reported | Not reported | |
| 5 (cognitive training ‐ group) | 1 | 5 | 60 | 300 | 5 | Group | Not reported | Not reported | |
| 6 (cognitive training ‐ individual) | 1 | 6 | Not reported | Not reported | Not reported | Individual | Not reported | Not reported | |
| NA (wait‐list control) | NA | NA | NA | NA | NA | NA | NA | NA | |
| 6 (cognitive training) | 1 | 6 | Not reported | Not reported | Not reported | Group, with a clinical neuropsychologist | 1 participant did not complete the first session, and 2 participants did not complete the fourth session | "All sessions were identical for all participants, with the memory group instructor relying on a trainer's manual with scripts for how to present the information" | |
| 6 (control) | 1 | 6 | 45 | 270 | 4.5 | Group, with a clinical neuropsychologist | 4 participants missed 1 session, and 1 participant missed 2 sessions | Not reported | |
| 4 (cognitive training) | 3 | 12 | 60 | 720 | 12 | Individual, with a neuropsychologist | Not reported | Not reported | |
| 4 (control) | 3 | 12 | 60 | 720 | 12 | Individual, with a neuropsychologist | Not reported | Not reported | |
| 8 (cognitive training ‐ collaborative intervention) | 1 | 8 | 30 to 40 | Approx. 280 | Approx. 4.5 | Dyads, with a research assistant | Not reported | Not reported | |
| 8 (cognitive training ‐ individual intervention) | 1 | 8 | 30 to 40 | Approx. 280 | Approx. 4.5 | Individual, with a research assistant | Not reported | Not reported | |
| NA (control group) | NA | NA | NA | NA | NA | NA | NA | NA | |
| 24 (cognitive training) | 2 to 6 | 48 to 144 | Approx. 20 | 960 to 2880 | 16 to 48 | Individual, with the possibility to ask staff members for advice | Not reported | Not reported | |
| NA (control) | NA | NA | NA | NA | NA | NA | Not reported | Not reported | |
| 2 (cognitive training ‐ recollection) | 12 | 24 | 60 | 1440 | 24 | Not reported | Not reported | Not reported | |
| 2 (cognitive training ‐ recognition) | 12 | 24 | 60 | 1440 | 24 | Not reported | Not reported | Not reported | |
| NA (control) | NA | NA | NA | NA | NA | NA | NA | NA | |
| 12 (cognitive training ‐ BBA) | 3 | 36 | 60 | 2160 | 36 | Individual, with an OT and a psychologist | Not reported | Not reported | |
| 12 (cognitive training ‐ IPP) | 3 | 36 | 60 | 2160 | 36 | Individual, with an OT and a psychologist | Not reported | Not reported | |
| NA (control) | NA | NA | NA | NA | NA | NA | NA | NA | |
| 12 (cognitive training) | 1 | 12 | 50 | 600 | 10 | Individual, with a neuropsychologist. | Not reported | Not reported | |
| 12 (control) | 1 | 12 | 50 | 600 | 10 | Individual, with a clinical psychologist. | Not reported | Not reported | |
| 12 (cognitive training) | 2 | 24 | 60 | 1440 | 24 | Group, provided by a neuropsychologist | Not reported | Not reported | |
| 12 (control) | 2 | 24 | 60 | 1440 | 24 | Group, provided by a neuropsychologist | Not reported | Not reported | |
| 20 (cognitive training) | 5 | 100 | 120 | 12000 | 200 | Group, supervised by a neuropsychologist | Not reported | Not reported | |
| 20 (control) | Presumed to be 5 | Not reported | Not reported | Not reported | Not reported | Group | Not reported | Not reported | |
| 6 (cognitive training ‐ CELP) | 2 | 12 | 30 | 360 | 6 | Individual, with a therapist | Not reported | Not reported | |
| 6 (cognitive training ‐ TELP) | 2 | 12 | 30 | 360 | 6 | Individual, with a therapist | Not reported | Not reported | |
| 6 (active control) | 2 | 12 | 30 | 360 | 6 | Not reported | Not reported | Not reported | |
| 8 (cognitive training) | 5 | 40 | 60 | 2400 | 40 | With a therapist | Not reported | Not reported | |
| 8 (control ‐ occupational therapy) | 5 | 40 | 60 | 2400 | 40 | Not reported | Not reported | Not reported | |
| NA (control ‐ usual care) | NA | NA | NA | NA | NA | NA | NA | NA | |
| 12 (cognitive training ‐ LSS‐tele) | 2 | 24 | 60 | 1440 | 24 | Small groups, provided by a therapist | Not reported | Not reported | |
| 12 (cognitive training ‐ LSS‐direct) | 2 | 24 | 60 | 1440 | 24 | Small groups, provided by a therapist | Not reported | Not reported | |
| 12 (control) | 2 | 24 | 60 | 1440 | 24 | Small groups, provided by a therapist | Not reported | Not reported | |
| 104 (cognitive training) | 3 (IPP) | 288 | 90 | 25920 | 432 | Group, with a clinical psychologist | Not reported | Not reported | |
| 104 (muscular relaxation) | 3 | 288 | 90 | 25920 | 432 | Group, with a clinical psychologist | Not reported | Not reported | |
| 104 (mindfulness) | 3 | 288 | 90 | 25920 | 432 | Group, with a clinical psychologist | Not reported | Not reported | |
| NA (passive control) | NA | NA | NA | NA | NA | NA | Not reported | Not reported | |
| 8 (cognitive training) | 1 | 8 | 60 | 480 | 8 | Individual and in a group | Not reported | Not reported | |
| 8 (control) | 1 | 8 | 60 | 480 | 8 | Not reported | Not reported | Not reported | |
| 96 (cognitive training) | 1 (during the first 3 months); 1 every 6 weeks (for the next 21 months) | 15 | 90 | 1350 | 22.5 | Groups | Not reported | Manual detailing the guidelines of each intervention was provided. Standardised procedures to guarantee homogeneity. Professional visits to therapists to ensure that interventions were applied in accordance with protocol | |
| NA (control ‐ usual care) | NA | NA | NA | NA | NA | NA | NA | NA | |
| 96 (reminiscence therapy) | 1 (during the first 3 months); 1 every 6 weeks (for the next 21 months) | 15 | 90 | 1350 | 22.5 | Groups | Not reported | Manual detailing the guidelines of each intervention was provided. Standardised procedures to guarantee homogeneity. Professional visits to therapists to ensure that interventions were applied in accordance with protocol | |
| 96 (cognitive rehabilitation) | 1 (during the first 3 months); 1 every 6 weeks (for the next 21 months) | 15 | 90 | 1350 | 22.5 | Individual | Not reported | Manual detailing the guidelines of each intervention was provided. Standardised procedures to guarantee homogeneity. Professional visits to therapists to ensure that interventions were applied in accordance with protocol | |
| 12 (cognitive training) | 3 | 36 | 30 | 1080 | 18 | Individual, with a neuropsychologist | Not reported | Not reported | |
| 12 (control) | 3 | 36 | 30 | 1080 | 18 | Individual, with a neuropsychologist | Not reported | Not reported | |
| 6 (cognitive training ‐ spaced retrieval) | 5 | 30 | 40 | 1200 | 20 | With a trainer | Not reported | Not reported | |
| 6 (cognitive training ‐ spaced retrieval+Montessori activities) | 5 | 30 | 40 | 1200 | 20 | With a trainer | Not reported | Not reported | |
| na (control) | NA | NA | NA | NA | NA | NA | NA | NA | |
| 12 (cognitive training) | 2 | 24 | 60 | 1440 | 24 | Small groups, provided by a cognitive therapist | Not reported | Not reported | |
| 12 (control) | NA | NA | NA | NA | NA | NA | NA | NA | |
| 10 (cognitive training) | 1 | 10 | 45 | 450 | 7.5 | Individually, with homewrok exercises with support of a caregiver | Not reported | Not reported | |
| 10 (control) | 1 | 10 | 45 | 450 | 7.5 | Not reported | Not reported | Not reported | |
| 12 (cognitive training) | 5 | 60 | 60 | 3600 | 60 | Performed in collaboration with patients’ caregivers | 85±12% in the CT group | Not reported | |
| 12 (aerobic exercise) | 5 | 60 | 60 | 3600 | 60 | Performed in collaboration with patients’ caregivers | 78±8% in the AE group | Not reported | |
| 12 (aerobic exercise+cognitive training) | 5 | 60 | 60 | 3600 | 60 | Performed in collaboration with patients’ caregivers | 75±14% in the AE+CT group | Not reported | |
| NA (control) | NA | NA | NA | NA | NA | NA | NA | NA | |
| 16 (cognitive training) | 3 | 48 | 90 | 4320 | 72 | Individual with licensed psychologist | Not reported | Not reported | |
| 16 (cognitive stimulation) | 3 | 48 | 90 | 4320 | 72 | Individual with licensed psychologist | Not reported | Not reported | |
| 16 (control) | NA | NA | NA | NA | NA | NA | Not reported | Not reported | |
| 12 (cognitive training) | 5 | 60 | Approx. 15 | Approx. 900 | Approx. 15 | Individual homework, with 1 meeting per month | 100% | Not reported | |
| 12 (cognitive rehabilitation) | 2 | 24 | 60 | 1440 | 24 | Small group guided by a psychologist and an occupational therapist | 100% (including only the 8 participants who completed the study and were, therefore, analysed) | Intervention was based on the CORDIAL programme, via a manual‐guided approach | |
| 12 (cognitive training) | 2 | 24 | 45 | 1080 | 18 | Small groups of 3 participants, guided by a neuropsychologist | Not reported | CT was co‐ordinated by a neuropsychologist using defined materials and procedures | |
| 12 (music therapy) | 2 | 24 | 45 | 1080 | 18 | Small groups of 3 participants, guided by a music therapist | Not reported | Active music therapy was provided by a music therapist. Sessions were videotaped and evaluated via a structured assessment | |
| 12 (neuroeducation) | 2 | 24 | 45 | 1080 | 18 | Small groups of 3 participants, co‐ordinated by a neurologist | Not reported | Not reported | |
| 3‐4 (VR group ‐ AD) | 3 | 10 | 20 | 200 | 3.3 | Individual with a neuropsychologist | Not reported | Not reported | |
| 3‐4 (VR group ‐ normal ageing) | 3 | 10 | 20 | 200 | 3.3 | Individual with a neuropsychologist | Not reported | Not reported | |
| NA (control) | NA | NA | NA | NA | NA | Underwent traditional cognitive rehabilitative activities with the neuropsychological staff | NA | NA | |
| 24 (cognitive training) | 2 | 48 | 75 | 3600 | 60 | Group | 11% (6 participants) attended less than 80% of sessions of the first period of the study (from T0 to T1). | Study authors reported high adherence to a strict protocol | |
| NA | NA | NA | NA | NA | NA | NA | NA | NA | |
| 12 (cognitive training) | 2 | 24 | 45 | 1080 | 18 | Group/individual when required | Mean attendance at 22 (92%) sessions | CT was administered by trained psychology students under the supervision of an experienced neuropsychologist | |
|
| NA (control) | NA | NA | NA | NA | NA | NA | NA | NA |
AChEI: anti‐cholinesterase inhibitor.
AD: Alzheimer's disease.
BBA: Big Brain Academy.
CELP: computerised errorless learning‐based memory training programme.
ChEI: cholinesterase inhibitor.
CT: cognitive traininng.
IPP: Integrated Psychostimulation Program.
LSS: lexical‐semantic simulation.
NA: not applicable.
TELP: therapist‐led errorless programme.
VR: virtual reality.
General characteristics of participants
Participants in all trials had a diagnosis of mild to moderate dementia according to the published paper. Diagnosis was based exclusively on NINCDS‐ADRDA criteria in 12 of the included trials, whereas six studies used either NINCDS‐ADRDA or DSM‐IV criteria, and one study used either NINCDS‐ADRDA or Milan Overall Dementia Scale (MODS) criteria. In four studies, diagnoses were supported by scores on the Mini Mental State Examination (MMSE) test alone, and one study used MMSE in combination with the Global Deterioration Scale (GDS). Two studies used DSM‐IV alone, three used the Clinical Dementia Rating Scale (CDR) alone, and one used the Chinese version of the Dementia Rating Scale (DRS) alone. Two studies used the DRS in combination with the GDS, and one study used physician judgement as the basis for diagnosis. In almost all trials, the presumed aetiology was AD, but other aetiologies were suspected in some studies: probable mixed dementia (Beck 1988); cardiovascular dementia or Parkinson's disease (Quayhagen 2000); vascular dementia (Neely 2009); and Parkinson's disease, vascular dementia, Lewy body dementia, or unknown dementia (Kallio 2018). With the exception of a small number of studies in which participants were recruited from hospital or nursing home facilities (Beck 1988; Cavallo 2016; Kawashima 2005; Mapelli 2013; Venturelli 2016), participants generally resided in the community. Severity of dementia among participants residing in a nursing home environment may have been somewhat greater, with MMSE scores ranging between 15 and 20 in Beck 1988, between 7 and 30 in Kawashima 2005, between 14 and 24 in Mapelli 2013, and between 10 and 15 in Venturelli 2016.
In two studies, the mean age of participants was greater than 65, but less than 70 years (Heiss 1993; Goudour 2011). In 19 of the included studies, the mean age of participants was between 70 and 80 years (Cavallo 2016; Quayhagen 1995; Tsantali 2017). In ten of the included trials, the mean age of participants was greater than 80 years (Boller 2011; Kawashima 2005; Kallio 2018). Two studies did not report the mean age of participants although, in both of them, they were 50 years and above (Brueggen 2017; Lee 2013)
General characteristics of experimental interventions
All studies included at least one condition that met our criteria for CT. In six studies, two conditions met our criteria for CT (Boller 2011; Fernández‐Calvo 2011; Jelcic 2014; Koltai 2001; Lee 2013; Neely 2009), and for these studies, data from the two conditions were combined as specified in the protocol to form a single experimental condition. Of a total of 39 CT interventions, 26 were classified as multi‐domain interventions and 13 as single‐domain interventions (Boller 2011; Cahn‐Weiner 2003; Davis 2001; Goudour 2011; Jelcic 2012; Jelcic 2014; Kao 2016; Lee 2013; Neely 2009). We classified most experimental interventions as 'straight CT', but we classified 13 experimental interventions as 'augmented CT' due to the inclusion of additional elements, usually associated with reality orientation, cognitive stimulation, or cognitive rehabilitation, as was the case with de Vreese 1998 or Davis 2001, Mapelli 2013 or Kim 2015, for example. We classified 23 of the 39 experimental interventions as primarily individual training (although in some cases, participants could receive some assistance from their caregivers) and 11 as group training. Two experimental conditions involved a combination of group and individual training (Kallio 2018; Kim 2015), and one experimental treatment involved dyads (Neely 2009). The remaining studies provided insufficient detail to show whether participants in the experimental conditions were trained individually or in a group (Boller 2011; Kao 2016).
General characteristics of comparison conditions
In seven studies, two conditions met our criteria for a comparison condition (Brueggen 2017; de Vreese 1998; Giovagnoli 2017; Kao 2016; Mapelli 2013; Venturelli 2016; Tsantali 2017). In a further two studies (Amieva 2016; Quintana Hernandez 2014), three conditions met our criteria for comparison conditions, and in one study (Quayhagen 2000), four conditions could be classified as comparison conditions. We classified 17 of the comparison conditions as passive controls (involving a wait‐list condition, a no‐contact condition, placebo medication, or usual care (i.e. continuing with usual activities of the nursing home or hospital, or receiving conventional medical care)) and 14 as active controls (including social support groups, activities similar to those in the experimental condition but with a passive approach, unstructured conversation or discussion, educational information, semi‐structured interviews, clinical support, unstructured or non‐specific cognitive activity, and other non‐specific activities). We considered that 15 interventions met our criteria for an alternative treatment. These included a new medication (de Vreese 1998); dyadic counselling, dual supportive seminar groups, and early‐stage daycare programmes (Quayhagen 2000); occupational therapy (Mapelli 2013); mindfulness and muscular relaxation (Quintana Hernandez 2014); reminiscence therapy and cognitive rehabilitation (Amieva 2016; Brueggen 2017); and spaced retrieval combined with Montessori activities (Kao 2016), aerobic exercise (Venturelli 2016), cognitive stimulation (Tsantali 2017), and music therapy and neuroeducation (Giovagnoli 2017).
Intervention dose and duration
The duration of interventions ranged from two weeks in Boller 2011 to approximately 104 weeks in Quintana Hernandez 2014. In seven of the 33 studies, the intervention lasted three months or longer (Amieva 2016; Bergamaschi 2013; Heiss 1993; Kawashima 2005; Quintana Hernandez 2014; Trebbastoni 2018; Tsantali 2017). In nine studies, researchers delivered the intervention in more than three sessions per week (Bergamaschi 2013; Boller 2011; Brueggen 2017; Kao 2016; Kawashima 2005; Mapelli 2013; Quayhagen 1995; Quintana Hernandez 2014; Venturelli 2016).
Excluded studies
We have summarised the characteristics of excluded studies in the Characteristics of excluded studies table.
Risk of bias in included studies
We have summarised risk of bias for individual studies, along with a justification for our ratings, in the Characteristics of included studies tables. We have summarised risk of bias for specific domains across studies in Figure 2 and Figure 3.
Risk of bias graph: review authors' judgements about each risk of bias item presented as percentages across all included studies.
Risk of bias summary: review authors' judgements about each risk of bias item for each included study.
Allocation
Although all studies are described as randomised trials, many studies provided insufficient detail regarding the randomisation procedure to determine whether the sequence was indeed random; accordingly we rated these as having unclear risk of bias. We rated two studies as having high risk of selection bias, generating the sequence in a manner that was unlikely to be truly random (Galante 2007; Jelcic 2014). We rated studies in which a remote, computerised randomisation method was carried out as low risk in relation to allocation concealment, as this is intrinsic to the method (e.g. Amieva 2016; Kallio 2018). However, we assumed that allocation was not concealed in studies that generated the sequence in a manner that did not guarantee allocation concealment or that provided insufficient detail concerning the randomisation procedure, and did not state explicitly that allocation was concealed (e.g. Beck 1988; Kawashima 2005).
Blinding
In most studies, post‐intervention assessments were performed by research staff, who were unaware of the condition to which participants were assigned, although a small number of studies provided insufficient detail to ensure that this was done (Kawashima 2005; Quayhagen 1995; Quintana Hernandez 2014). However, in approximately 25% of trials (Barban 2016; Beck 1988; Boller 2011; Brueggen 2017; Giuli 2016; Heiss 1993; Koltai 2001; Neely 2009; Serino 2017), unmasked personnel completed outcome assessments, leading to increased risk of detection bias. In relation to performance bias, because blinding of those delivering the intervention typically is not possible in studies of CT, we focused our assessment of risk on the extent to which participants were blinded to whether they were assigned to an experimental or control intervention. This is not possible in studies that included only a passive (e.g. treatment as usual) control condition; we therefore rated these studies as having high risk of performance bias. We rated studies that used an active control or an alternative treatment as having unclear risk of performance bias if no mention was made of an attempt to mask whether the allocated condition was an experimental or control intervention. We rated approximately 90% of studies as having high or unclear risk of performance bias.
Incomplete outcome data
In approximately 50% of the included studies, we found no evidence of attrition bias; however, we judged about half of the remaining studies to have unclear risk (e.g. Giovagnoli 2017; Quayhagen 2000), and we judged half to be at high risk of bias due to attrition (e.g. de Vreese 1998; Tsantali 2017).
Selective reporting
In most cases, studies seem to have reported all outcomes, or study authors provided them in the required format upon request. We sought information from trial registries to determine whether all pre‐specified outcomes were reported, but we found no published protocols for any of the included studies.
Effects of interventions
See: Summary of findings for the main comparison Cognitive training compared to control immediately post intervention for people with mild to moderate dementia; Summary of findings 2 Cognitive training compared to control in the medium term (3 to 12 months post intervention) for people with mild to moderate dementia; Summary of findings 3 Cognitive training compared to alternative treatment immediately post intervention for people with mild to moderate dementia; Summary of findings 4 Cognitive training compared to alternative treatment in the medium term (3 to 12 months post intervention) for people with mild to moderate dementia
We summarised main outcomes when CT was compared with control interventions at end of treatment in summary of findings Table for the main comparison.
We summarised main outcomes when CT was compared with control interventions in the medium term in summary of findings Table 2.
We summarised main outcomes when CT was compared with alternative treatments at end of treatment in summary of findings Table 3.
We summarised main outcomes when CT was compared with alternative treatments in the medium term in summary of findings Table 4.
Participant outcomes
Global cognition (composite outcome measure) at end of treatment (primary outcome) and in the medium term (secondary outcome)
Comparison with control
We found a small to moderate effect favouring CT relative to a control condition on the primary outcome, namely, global cognition measured with a composite cognitive score at end of training (standardised mean difference (SMD) 0.42, 95% confidence interval (CI) 0.23 to 0.61; 27 trials; 1389 participants; Analysis 1.1; Figure 4). Our certainty in this finding is moderate due to heterogeneity in effect estimates, which was not explained by planned subgroup analyses. We did not detect clear evidence of publication bias when examining the funnel plot in Figure 5. We performed a more conservative sensitivity analysis in which we assumed no correlation between observations before and after the intervention and still found moderate‐quality evidence of a small beneficial effect of CT relative to a control on global cognition at end of treatment (SMD 0.24, 95% CI 0.12 to 0.36; Analysis 1.2).
Forest plot of comparison: 1 Cognitive training vs control immediately post intervention, outcome: 1.1 Change in a global measure of cognition (composite).
Funnel plot of comparison: 1 Cognitive training vs control immediately post intervention, outcome: 1.1 Change in a global measure of cognition (composite).
We were uncertain whether CT had an effect relative to a control condition on a composite measure of global cognition in the medium term (i.e. between 3 and 12 months post treatment) due to the very low quality of evidence, both in our main analysis (SMD 0.65, 95% CI 0.11 to 1.2, 8 trials; 387 participants; Analysis 2.1) and in a sensitivity analysis in which we assumed no correlation between observations before and after the intervention (SMD 0.40, 95% CI 0.09 to 0.71; Analysis 2.2). Quality concerns were related to risk of bias, heterogeneity, and imprecision.
Comparison with an alternative treatment
In comparison with an alternative treatment, we found no clear evidence of an effect of CT on a global measure of cognition at end of treatment, but the quality of evidence for this finding is low due to very serious imprecision (SMD 0.21, 95% CI ‐0.23 to 0.64; 7 trials; 769 participants; Analysis 3.1; Figure 6). In a more conservative sensitivity analysis, assuming zero correlation between observations before and after the intervention, we found there may be little or no effect of CT (SMD ‐0.03, 95% CI ‐0.23 to 0.17; Analysis 3.2) on a composite global cognition score at end of training. The quality of evidence related to this outcome is also low.
Forest plot of comparison: 3 Cognitive training vs alternative treatment immediately post intervention, outcome: 3.1 Change in a global measure of cognition (composite).
In the medium term, we were unable to determine whether CT was associated with any gains in global cognition relative to an alternative treatment because of the very low quality of evidence (SMD 1.31, 95% CI ‐1.03 to 3.65; 2 studies; 73 participants; Analysis 4.1Analysis 4.2).
Global cognition (screening measures) at end of treatment and in the medium term (secondary outcomes)
Comparison with control
Findings were similar when global cognition was assessed using a screening measure, typically the MMSE (although nine studies used another measure as well as the MMSE, including the Alzheimer's Disease Assessment Scale ‐ cognitive subscale (ADAS‐Cog), the Milan Overall Dementia Scale (MODA), the Cambridge Cognitive Assessment (CAMCOG), and the complete neuropsychological battery (ENB‐2), and one study used only the ADAS‐Cog). We found low‐quality evidence suggesting a moderate effect of CT on global cognition at end of training (SMD 0.65, 95% CI 0.26 to 1.05; 20 trials; 1288 participants; Analysis 1.3; Figure 7) and a smaller but still beneficial effect in our more conservative sensitivity analysis (SMD 0.27, 95% CI 0.04 to 0.50; Analysis 1.4).
Forest plot of comparison: 1 Cognitive training vs control immediately post intervention, outcome: 1.3 Change in a global measure of cognition.
We are unable to determine whether there is any effect on global cognition assessed with screening measures in the medium term due to the very low quality of evidence, including following a sensitivity analysis (6 trials; 387 participants; Analysis 2.3Analysis 2.4). Quality concerns were related to risk of bias, heterogeneity, and imprecision.
Comparison with an alternative treatment
We are uncertain of any effect of CT on a global measure of cognition when compared to an alternative treatment immediately after the intervention due to the very low quality of evidence (SMD 0.16, 95% CI ‐0.28 to 0.60; 7 trials; 724 participants; Analysis 3.3). This was also true in the medium term (SMD 3.20, 95% CI ‐2.89 to 9.29; 2 trials; 73 participants; Analysis 4.3).
Subgroup analyses
To explore the sources of heterogeneity in our main comparison for global cognition, we performed several pre‐specified subgroup analyses, including type of control condition (see Analysis 10.3), type of CT (see Analysis 8.3; Analysis 9.3), dose delivered (frequency and duration; see Analysis 6.3; Analysis 7.3), and risk of bias (see Analysis 5.3). We found no significant differences between subgroups in any of the subgroup analyses in relation to global cognition, although we found non‐significant trends suggesting that trials in which the intervention was delivered at a frequency greater than three times per week were associated with larger effects than trials in which the intervention was delivered up to three times per week (Analysis 6.3), and that traditional CT trials were associated with larger effect sizes than 'augmented' CT trials (Analysis 8.1).
Clinical disease severity at end of treatment (secondary outcome)
Comparison with control
We found a large effect of CT relative to a control condition on the secondary outcome of clinical disease severity at end of treatment (SMD 1.07, 95% CI 0.59 to 1.55; 6 trials; 215 participants; Analysis 1.5). However, owing to concerns regarding heterogeneity and imprecision, our certainty in the accuracy of the estimate is low.
Comparison with an alternative treatment
When compared with an alternative treatment, we found no evidence of an effect of CT on clinical disease severity, and the quality of the evidence was low due to very serious imprecision (SMD 0.15, 95% CI ‐0.33 to 0.63; 3 trials; 131 participants; Analysis 3.5).
Clinical disease severity in the medium term (primary outcome)
Comparison with control
We were unable to determine whether there is an effect of CT relative to a control intervention on the primary outcome of clinical disease severity in the medium term (3 to 12 months post treatment), as the quality of the evidence is very low due to concerns regarding risk of bias and imprecision (SMD 0.55, 95% CI 0.12 to 0.98; 2 trials; 98 participants; Analysis 2.5Figure 8). We performed a sensitivity analysis in which a conservative assumption of no correlation between observations before and after the intervention was applied to the data, and we were again unable to determine whether there was any effect of CT relative to a control condition on clinical disease severity in the medium term due to the very low quality of evidence (SMD 0.28, 95% CI ‐0.14 to 0.71; Analysis 2.6).
Forest plot of comparison: 2 Cognitive training vs control in the medium term (3 to 12 months post intervention), outcome: 2.5 Change in disease progression.
Comparison with an alternative treatment
None of the included studies measured this outcome in the medium term.
Specific cognitive domains (secondary outcomes)
Comparison with control
Results comparing effects CT versus a control condition at end of treatment on specific cognitive domains (secondary outcomes) are depicted in Analysis 1.6Analysis 1.7Analysis 1.8Analysis 1.9Analysis 1.10Analysis 1.11Analysis 1.12Analysis 1.13 and Figure 9. CT showed a positive effect in immediate and delayed memory, attention and working memory, language (naming), executive functions, and verbal category fluency immediately after the intervention. However, with the exception of findings regarding category fluency (high certainty), our certainty in findings concerning specific cognitive domains was generally very low to low. As can also be seen in Analysis 2.7Analysis 2.8Analysis 2.9Analysis 2.10Analysis 2.11Analysis 2.12Analysis 2.13 and Analysis 2.14, gains in some of the specific cognitive domains (delayed memory, naming, executive functions, and verbal category fluency) were maintained in the medium term. However, again, with the exception of category fluency scores (high certainty), our certainty in these findings ranges from low to very low.
We performed pre‐specified subgroup analyses to explore effects of sources of heterogeneity in the comparison of CT versus control interventions on scores in specific cognitive domains, including high risk of bias studies versus lower risk of bias studies, type of CT (traditional vs augmented), type of domain (multi‐domain vs single domain), and type of control group (passive vs active). Subgroup analyses suggest that the intervention dose moderated effects of CT on verbal letter fluency (Chi² = 3.96, df = 1, P = 0.05), and larger effects were associated with interventions delivered more than three times per week (SMD 1.0, 95% CI 0.09 to 1.92; 3 trials; 84 participants) relative to interventions delivered up to three times per week (SMD 0.05, 95% CI ‐0.13 to 0.24; 9 trials; 460 participants; Analysis 6.9; Figure 10). In addition, subgroup analyses suggest that type of CT moderated effects on verbal category fluency (Chi² = 4.81, df = 1, P = 0.03), and multi‐domain training was associated with larger effects (SMD 0.70, 95% CI 0.38 to 1.02; 6 trials; 371 participants) than single‐domain training (SMD 0.14, 95% CI ‐0.25 to 0.52; 3 trials; 104 participants; Analysis 9.12; Figure 11). We found no other explanations of heterogeneity in other subgroup analyses.
Forest plot of comparison: 1 Cognitive training vs control immediately post intervention, outcome: 1.6 Change in delayed memory.
Forest plot of comparison: 6 Cognitive training vs control immediately post intervention ‐ intervention dose, outcome: 6.9 Change in verbal letter fluency.
Forest plot of comparison: 9 Cognitive training vs control immediately post intervention ‐ type of CT (multi‐domain vs single domain), outcome: 9.12 Change in verbal category fluency.
Comparison with an alternative treatment
Results comparing effects of CT versus an alternative treatment at end of treatment on specific cognitive domains are depicted in Analysis 3.6Analysis 3.7Analysis 3.8Analysis 3.9Analysis 3.10Analysis 3.11Analysis 3.12 and Analysis 3.13. Due to the very low quality of evidence, we could not determine whether CT is associated with any benefit for specific cognitive domains compared with an alternative treatment at the end of the intervention. Results for comparison of CT versus an alternative treatment in the medium term are depicted in Analysis 4.6Analysis 4.7Analysis 4.8Analysis 4.9Analysis 4.10Analysis 4.11Analysis 4.12 and Analysis 4.13. As can be seen, with the exception of immediate and delayed memory, other specific cognitive domains were evaluated by a single study; therefore we could not perform meta‐analyses. The quality of evidence in relation to all of these outcomes was low to very low, so we are unable to determine whether, relative to an alternative treatment, CT is associated with any gains in specific cognitive domains in the medium term.
Meta cognition ‐ self‐reported (secondary outcome)
Comparison with control
We found no evidence that CT had an effect on self‐rated cognitive ability immediately post treatment (SMD 0.12, 95% CI ‐0.87 to 1.12; 2 trials; 41 participants; Analysis 1.14; Analysis 2.15). However, the quality of evidence was low, and the findings were very imprecise. Data for this outcome in the medium term were available from only one trial (Lee 2013), in which participants in the experimental condition (which combined data from two experimental conditions ‐ a computerised version and a non‐computerised version of the training) reported fewer difficulties related to prospective memory following treatment relative to control. However, this is a very small trial (n = 19), which we rated to be at high risk of attrition bias due to incomplete outcome data and at high risk of selection bias due to lack of allocation concealment. Given the subjective nature of the outcome, and use of a 'no treatment' control condition, our certainty in this finding is very low. Therefore, we are unable to determine whether CT is associated with any gains in meta cognition in the medium term relative to a control treatment.
Comparison with an alternative treatment
Data concerning this outcome were not available in the comparison of CT versus an alternative treatment in the immediate or medium term.
Meta cognition ‐ informant‐reported (secondary outcome)
Comparison with control
We are unable to determine whether relative to a control condition, CT had an effect on informant‐rated cognitive ability immediately post training due to very low quality of the evidence (SMD ‐0.01, 95% CI ‐1.29 to 1.26; 2 trials; 56 participants; Analysis 1.15). In the medium term, a single study found no evidence of an effect of CT on informant‐rated cognition in the medium term (SMD ‐0.06, 95% CI ‐0.73 to 0.62; Analysis 2.16), but the quality of the evidence was low (Cahn‐Weiner 2003).
Comparison with an alternative treatment
No studies contributed to this outcome when comparing CT versus alternative treatments in the immediate or medium term.
Mood (secondary outcome)
Comparison with control
We are unable to determine whether relative to a control condition, CT had an effect on participants' mood, as reflected on measures of depression, because the quality of the evidence was very low due to concerns related to inconsistency and imprecision (SMD 0.72, 95% CI ‐0.10 to 1.54; 8 trials; 577 participants; Analysis 1.16, Figure 12). We found no evidence of an effect of CT over a control condition in the medium term. The quality of evidence was low due to very serious imprecision; thus, our results were inconclusive (i.e. between 3 and 12 months post treatment; SMD 0.21, 95% CI ‐0.54 to 0.96; 2 trials; 30 participants; Analysis 2.17). We performed pre‐specified subgroup analyses to explore the sources of heterogeneity in participants’ mood when CT was compare with control, including type of control condition and type of CT (traditional vs augmented). The test for subgroup differences could not explain heterogeneity in traditional CT versus augmented CT (P = 0.64), nor in passive control versus active control (P = 0.71) (Analysis 8.15Analysis 10.15).
Forest plot of comparison: 1 Cognitive training vs control immediately post intervention, outcome: 1.16 Change in participants' mood.
Comparison with an alternative treatment
When compared with an alternative treatment, we found that CT probably had little or no effect on participants’ mood immediately post treatment; we are moderately certain of this finding (SMD ‐0.11, 95% CI ‐0.29 to 0.07; 3 trials; 543 participants; Analysis 3.16). Only one study contributed to this same outcome in the medium term (Giovagnoli 2017); therefore we could not perform a meta‐analysis. Results of this study suggest that benefits in the medium term may favour an alternative treatment (SMD ‐0.66, 95% CI ‐1.35 to 0.02). However, due to very serious concerns related to imprecision, the quality of the evidence was low; therefore, the results are inconclusive.
Capacity for activities of daily living (secondary outcome)
Comparison with control
Relative to a control intervention, we found that CT may have little to no effect on capacity for activities of daily living immediately post treatment (SMD 0.12, 95% CI ‐0.11 to 0.35; 10 trials; 687 participants; Analysis 1.17Figure 13); however the quality of the evidence was low due to concerns related to risk of bias and imprecision. Therefore clear evidence is lacking.
Forest plot of comparison: 1 Cognitive training vs control immediately post intervention, outcome: 1.17 Change in capacity for activities of daily living.
We also found no evidence that CT has an effect on activities of daily living in the medium term (SMD 0.22, 95% CI ‐0.5 to 0.94; 3 trials; 64 participants; Analysis 2.18); the quality of evidence was again low due to very serious concerns regarding imprecision. Therefore clear evidence is lacking.
Comparison with an alternative treatment
We are moderately certain that CT, when compared with an alternative treatment, has little or no effect on participants' capacity for activities of daily living at end of treatment (SMD ‐0.25, 95% CI ‐0.43 to ‐0.07; 3 trials; 525 participants; Analysis 3.17). No studies evaluated this outcome in the medium term.
General health and quality of life (secondary outcome)
Comparison with control
Because the quality of evidence was very low, we are unable to determine whether, relative to a control condition, CT had an effect on general health and quality of life immediately post intervention (SMD ‐0.04, 95% CI ‐0.38 to 0.29; 5 trials; 630 participants; Analysis 1.18). In the medium term, only one study contributed to this outcome; therefore, we could not perform a meta‐analysis (Kallio 2018). This study found no evidence of any CT relative to a control condition (SMD ‐0.02, 95% CI ‐0.39 to 0.35; Analysis 2.19), but the quality of the evidence was low due to very serious imprecision.
Comparison with an alternative treatment
In comparison with an alternative treatment, the quality of the evidence was low. We found that an alternative treatment may be favoured, but these results were imprecise, so there could be little or no effect of CT immediately post intervention (SMD ‐0.49, 95% CI ‐1 to 0.02; 4 trials; 631 participants; Analysis 3.18). Only one study contributed to this outcome in the medium term, finding no evidence of a positive effect of CT relative to alternative treatment (SMD 0.33, 95% CI ‐0.34 to 1; Analysis 4.18), but the quality of evidence was low, so the results are inconclusive (Giovagnoli 2017).
Behavioural and psychological symptoms of dementia (secondary outcome)
Comparison with control
The quality of the evidence was very low due to serious concerns related to heterogeneity and imprecision, so we are unable to determine whether, relative to a control treatment, CT had an effect on behavioural and psychological symptoms of dementia immediately post intervention (SMD 0.44, 95% CI ‐0.34 to 1.22; 6 trials; 493 participants).
In the medium term, only one study contributed to this outcome and found no evidence of an effect of CT on general health and quality of life (SMD ‐1.34, 95% CI ‐2.75 to 0.07; 1 trial; 11 participants; Analysis 2.20) (Galante 2007). However, we have low certainty in this result.
Comparison with an alternative treatment
We found moderate‐quality evidence showing that CT probably has no effect relative to an alternative treatment immediately post intervention (SMD ‐0.11, 95% CI ‐0.27 to 0.06; 3 studies; 672 participants; Analysis 3.19). No trials compared CT versus an alternative treatment on this outcome in the medium term.
Participant burden (retention rates at end of treatment) (secondary outcome)
Meta‐analyses of participant retention rates at end of treatment showed that participants receiving CT were not more likely to discontinue participating in the trial relative to participants receiving a control (odds ratio (OR) 0.73, 95% CI 0.37 to 1.43; 17 trials; 1282 participants; Analysis 1.20Figure 14) or an alternative treatment (OR 0.78, 95% CI 0.24 to 2.57; 4 trials; 639 participants; Analysis 3.20), but our certainty in these findings is very low to low due to imprecision; therefore, our results are inconclusive.
Forest plot of comparison: 1 Cognitive training vs control immediately post intervention, outcome: 1.20 Participant burden (retention rates).
Caregiver outcomes
Comparison with control
Results concerning caregiver outcomes are depicted in Analysis 1.21Analysis 1.22Analysis 1.23Analysis 3.21Analysis 3.22Analysis 3.23 and Figure 15. The quality of evidence in relation to quality of life of the caregiver immediately at the end of treatment was low, and we found no evidence of any effects of CT relative to a control condition (SMD 0.16, 95% CI ‐0.50 to 0.83; 1 trial; 36 participants; Analysis 1.22). We also found moderate‐quality evidence showing that CT was not associated with lower burden of care at end of treatment relative to a control treatment (SMD ‐0.11, 95% CI ‐0.36 to 0.15; 2 trials; 405 participants; Analysis 1.21). One study found a positive effect of CT on caregiver mood at end of treatment relative to control (SMD 0.98, 95% CI 0.27 to 1.68; 1 trial; 36 participants; Analysis 1.23) (Quayhagen 2000). We have moderate certainty in this finding.
Forest plot of comparison: 1 Cognitive training vs control immediately post intervention, outcome: 1.23 Change in mood and well‐being (CAREGIVER).
Comparison with an alternative treatment
Based on one study (Quayhagen 2000), we found moderate‐quality evidence of a positive effect of CT on caregiver mood at end of treatment relative to alternative treatment (SMD 1.5, 95% CI 0.96 to 2.04; 1 trial; 88 participants; Analysis 3.23). No available studies evaluated caregiver outcomes in the medium term.
Discusión
Resumen de los resultados principales
El objetivo de la presente revisión fue evaluar la evidencia actual con respecto a los efectos de las intervenciones de entrenamiento cognitivo (EC) sobre varios resultados clave para los pacientes con demencia leve a moderada; se encontraron 33 estudios que cumplieron los criterios de inclusión. Se realizaron comparaciones separadas del EC versus una intervención control (pasiva o activa) y del EC versus un tratamiento alternativo. Los resultados clave de esta revisión son que el EC probablemente tiene efectos positivos pequeños a moderados sobre la cognición global, así como sobre el dominio cognitivo específico de la fluidez semántica verbal inmediatamente después del tratamiento, y estas ganancias se pueden mantener a medio plazo en comparación con una intervención control pasiva o activa. Aunque se encontraron mejorías al final del tratamiento en varios otros dominios o procesos cognitivos, en general la certeza de la evidencia fue baja, por lo que la certeza en estos resultados es baja. Más allá de la cognición, el EC se puede asociar con una progresión clínica más lenta inmediatamente después del tratamiento y a medio plazo, pero nuevamente, no existe mucha certeza acerca de este resultado. No se encontró evidencia de un aumento de la carga de los participantes asociada con el EC (como se refleja en las tasas de interrupción). Se realizaron varios análisis de subgrupos preespecificados para explorar los posibles modificadores del efecto, pero se encontró que ninguno fue significativo.
Por otra parte, no se encontró evidencia sólida de cualquier efecto beneficioso asociado con el EC con respecto a otros tratamientos en cuanto a los resultados primarios cognición global al final del tratamiento y gravedad de enfermedades clínica a medio plazo, pero la certeza en muchos de estos resultados es baja. Tampoco se encontraron efectos beneficios asociados con el EC con respecto a cualquiera de los resultados secundarios incluidos en esta revisión y, de hecho, los tratamientos alternativos pueden haber sido favorecidos con relación a los síntomas del estado de ánimo, conductuales y psicológicos de los participantes, o a la capacidad para las actividades cotidianas, pero los resultados fueron imprecisos y la confianza en ellos es baja.
Compleción y aplicabilidad general de las pruebas
Números y fuentes de los estudios que cumplieron con los criterios de la revisión
La presente revisión incluyó 33 ensayos controlados aleatorios (ECA) con un total de 1924 participantes, lo que la hace la revisión sistemática más amplia sobre este tema realizada hasta la fecha. Dieciocho estudios, es decir, más de la mitad de todos los estudios incluidos, se publicaron desde 2013, cuando se publicó una revisión Cochrane anterior que cubrió los estudios de EC y solo incluyó diez (Bahar‐Fuchs 2013). El gran número de estudios publicado en años recientes fue algo inesperado, debido a que en años recientes el foco de muchos ensayos de intervención se ha desplazado a la fase predemencia de la deficiencia cognitiva leve (DCL) y a los adultos de edad avanzada sin deficiencias y con riesgo de demencia. Además, las revisiones anteriores, incluidas la revisión Cochrane y otras (p.ej. Hill 2017; Oltra‐Cucarella 2016), en general encontraron poca evidencia en apoyo del EC para los pacientes con demencia. Contra este contexto, el número cada vez mayor de ensayos de EC para los pacientes con demencia fue sorprendente, pero la disponibilidad de un número relativamente grande de estudios fortalece en general la certeza en los resultados de la presente revisión. Los estudios incluidos se realizaron en más de 12 países y, en la revisión actual, no se restringió la inclusión a los estudios publicados en inglés. Cabe señalar, sin embargo, que una gran mayoría de los estudios, en particular los publicados en los últimos años, se realizaron en países europeos, y 11 de ellos se realizaron solo en Italia. No se encontraron estudios elegibles realizados en países de habla inglesa como el Reino Unido, Canadá o Australia, y todos los estudios realizados en los EE.UU. se incluyeron en las revisiones anteriores a 2013. Las razones de esta tendencia no están claras, pero el grado en el que los resultados de la revisión actual son aplicables a los pacientes de otros países no está del todo claro.
Problemas relacionados con la definición y el alcance de las intervenciones
Aunque todas las intervenciones experimentales de los estudios incluidos se clasificaron como EC, las intervenciones fueron clínicamente heterogéneas; algunas se administraron mediante lápiz y papel y otras mediante plataformas computarizadas, unas se dirigieron a dominios cognitivos únicos y otras a dominios múltiples de manera simultánea, y unas se centraron principalmente en el simulacro y la práctica, mientras que otras utilizaron varias estrategias de aprendizaje y rendimiento. Los contextos y las dosis a las cuales se administraron las intervenciones también fueron diversos; algunas se administraron en el domicilio y otras en ámbitos comunitarios, incluidos la atención diurna y los contextos hospitalarios, y una se administró una o dos veces por semana y otros hasta cinco veces por semana. Por lo tanto, es más apropiado pensar que las intervenciones incluidas en la presente revisión consisten en una clase o familia de intervenciones con algunas características compartidas y, por lo tanto, que las intervenciones no miden exactamente el mismo efecto; lo anterior se refleja en la decisión de realizar un metanálisis de efectos aleatorios, que es más apropiado en estas circunstancias (Deeks 2017). Aunque es más probable que la heterogeneidad clínica sea responsable de parte de la heterogeneidad estadística observada en los cálculos del efecto de los ensayos individuales, los análisis de subgrupos preespecificados, realizados en los casos en los que se encontró al menos heterogeneidad moderada y un número suficiente de ensayos disponibles, no mostró evidencia sólida de diferencias que justificaría la realización de metanálisis separados para diferentes subgrupos.
Resultados y medidas
La presente revisión se centra en una gran cantidad de resultados primarios y secundarios para el paciente con demencia y para sus cuidadores, y se diferenció entre los resultados inmediatamente posintervención y los resultados informados a medio plazo (tres a 12 meses postratamiento). En los estudios los resultados se evaluaron con más de 200 medidas; sin embargo, en muchos casos una medida dada se contabilizó varias veces debido a diferencias menores en el nombre de los países o en las versiones del instrumento, o a que no se proporcionaron detalles suficientes para determinar qué medida exacta se utilizó. Cuando los estudios proporcionaron puntuaciones individuales de subpruebas de baterías de pruebas o índices globales, cada subprueba se contabilizó como una medida. En algunos casos los estudios utilizaron pruebas no publicadas desarrolladas para ese estudio en particular. En muchos casos fue difícil clasificar las medidas cognitivas en un único dominio cognitivo; muchos otros estudios utilizaron múltiples medidas del mismo dominio de resultado cognitivo, y se siguió un plan preespecificado (ver Problemas con la unidad de análisis en la sección Métodos) al seleccionar las medidas para el metanálisis. Aunque se reconoce que este método tiene limitaciones y es posible que no siempre haya dado lugar a una evaluación óptima de un dominio cognitivo determinado, este procedimiento se adoptó para reducir la probabilidad de sesgo introducido al seleccionar una medida sobre la base del tamaño del efecto.
El primer resultado primario (cambio en la capacidad cognitiva global [compuesta] inmediatamente postratamiento) se evaluó en 33 estudios, con un total de 1914 participantes. Por otra parte, el segundo resultado primario (cambio en la progresión de la enfermedad a medio plazo, un resultado que puede ser de mayor importancia para los pacientes con demencia y los encargados de tomar decisiones) solo se evaluó en dos estudios con un total de 98 participantes, mediante una escala de calificación de la gravedad de la demencia. Aunque los investigadores encontraron un efecto moderado del EC comparado con el tratamiento control con respecto al cambio en la gravedad clínica de la enfermedad, la certeza en este resultado es muy baja. Muchos otros resultados importantes (p.ej. cambio en el estado de ánimo del cuidador, carga o calidad de vida a medio plazo) se evaluaron en un único estudio, por lo que no fue posible realizar un metanálisis; otros resultados (p.ej. cambios en los síntomas conductuales y psicológicos a medio plazo, cambio en el estado de ánimo del cuidador después del tratamiento) se evaluaron en un número muy pequeño de estudios, o no se evaluaron en absoluto. Es importante señalar que, aunque fue posible realizar un metanálisis sobre la base de una gran cantidad de estudios y participantes para el resultado primario de cognición global, y a pesar de que los resultados indicaron al menos un efectos pequeño a moderado del EC con respecto a los tratamientos control, el grado en el que los efectos beneficiosos cognitivos observados fueron clínicamente significativos aún es poco claro. De hecho, no se encontró evidencia de que el EC da lugar a cambios en la capacidad de los pacientes de realizar actividades cotidianas inmediatamente postratamiento o a medio plazo, aunque la certeza de la evidencia fue baja, por lo que los resultados no son concluyentes.
Fidelidad de la intervención y cumplimiento del participante
Con frecuencia, el cumplimiento de un protocolo prescrito de intervención es una barrera para las intervenciones sobre el estilo de vida, particularmente no supervisadas, autoadministradas y proporcionadas en el domicilio, y la interpretación de los efectos reales de las intervenciones puede estar sesgada en el contexto de un cumplimiento subóptimo. Sin embargo, solo hubo referencia al cumplimiento con la intervención en una cantidad pequeña de los estudios, principalmente los recientes (Amieva 2016; Brueggen 2017; Cahn‐Weiner 2003; Giovagnoli 2017; Kallio 2018; Trebbastoni 2018), y ninguno definió el "cumplimiento" de manera prospectiva. Por lo tanto, es difícil saber cuán similares o distintas son las tasas de adherencia en los diferentes estudios y en qué medida los cálculos de los efectos en los estudios individuales fueron afectados por los problemas con el cumplimiento. De manera similar, con la excepción de una pequeña cantidad de estudios (Amieva 2016; Brueggen 2017; Cahn‐Weiner 2003; Giovagnoli 2017), ninguno hizo referencia a la adopción de medidas asociadas con la evaluación o la monitorización de la fidelidad con la cual se administró la intervención, incluido si se hizo algún cambio en el protocolo de la intervención después de haber comenzado el reclutamiento, si se siguió un manual para el protocolo de la intervención, o si los que administraron la intervención recibieron un adiestramiento específico. La falta de medidas adecuadas para asegurar la fidelidad tiene implicaciones para la replicabilidad de los estudios de intervenciones conductuales; por lo tanto, es más difícil saber si es probable que los resultados de un ensayo observados en un contexto se observen cuando la intervención se aplica en otro contexto.
Calidad de la evidencia
Se utilizaron los criterios GRADE para evaluar la confianza en los resultados de los estudios con respecto a los resultados principales de la presente revisión, con la incorporación de la calificación del riesgo de sesgo de los estudios incluidos, la inconsistencia y la imprecisión en los resultados, la direccionalidad de la evidencia y el sesgo de publicación (GRADE Handbook; GRADEpro GDT). Al comparar el EC con una intervención control, del gran número de resultados evaluados, solo existe una gran confianza en los hallazgos relacionados con un único resultado inmediatamente después del tratamiento, a saber, la fluidez de la categoría verbal. La confianza en los resultados de los ensayos fue moderada para varios otros resultados inmediatamente después de la intervención, incluido el resultado primario de cognición global medida con una puntuación compuesta, así como para los resultados de los cuidadores carga de la atención, estado de ánimo y bienestar. La certeza en los hallazgos de otros resultados, incluido el segundo resultado primario de evolución clínica a medio plazo, fue muy baja. Cuando el EC se comparó con un tratamiento alternativo, hubo confianza moderada con relación a los hallazgos sobre el cambio en los síntomas del estado de ánimo, conductuales y psicológicos de los participantes, y sobre la capacidad para las actividades cotidianas, así como para el estado de ánimo y el bienestar de los cuidadores al final del tratamiento. La confianza en los hallazgos de todos los otros resultados evaluados al final del tratamiento y a medio plazo es baja o muy baja.
Riesgo de sesgo
Aunque la mayoría de los estudios se calificaron como alto riesgo de sesgo en al menos dos dominios, el enfoque para la clasificación de los estudios en "alto" y "bajo" riesgo de sesgo para los análisis de subgrupos y la clasificación de la evidencia fue relativamente indulgente y dio lugar a que solo siete estudios se calificaran como "alto riesgo". Sin embargo, con la excepción de la "memoria inmediata" en la comparación primaria (EC versus intervención control inmediatamente posintervención), en la que los estudios clasificados como "alto riesgo" se asociaron con cálculos agrupados del efecto más pequeños en relación con los estudios con "bajo riesgo", el riesgo de sesgo no pareció influir mucho en la heterogeneidad de los cálculos del efecto. Los estudios de "alto riesgo" en esta revisión se predefinieron como los que se calificaron como "alto riesgo" en al menos dos dominios críticos. Para los fines de la revisión, los dominios críticos se definieron como la asignación al azar, el cegamiento de la evaluación del resultado, los datos de resultado incompletos y el informe selectivo. Se reconoce la importancia de la ocultación de la asignación y el cegamiento de los participantes y el personal. Sin embargo, la ocultación de la asignación se informa en pocas ocasiones en los ensayos de EC encontrados hasta la fecha, y la mayoría de los estudios se clasificarían como alto riesgo si este dominio se clasifica como un "dominio crítico". De manera similar, habitualmente el cegamiento de los que administraron las intervenciones no es posible en los ensayos de esta naturaleza y el cegamiento de los participantes solo se puede intentar en los ensayos con un control activo o un tratamiento alternativo.
Inconsistencia
Con relación a los resultados primarios, la calidad de la evidencia de los hallazgos sobre la cognición global se disminuyó en 1 punto debido a inquietudes graves con respecto a la inconsistencia cuando el EC se comparó con un grupo control inmediatamente después de la intervención, pero no se encontraron estos problemas cuando el EC se comparó con un tratamiento alternativo. Para la progresión de la enfermedad a medio plazo, nuevamente no se encontraron problemas relacionados con la inconsistencia. Para la mayoría de los otros resultados la inconsistencia se valoró como no grave, debido habitualmente a la heterogeneidad relativamente pequeña o moderada, que se explicó al menos en parte en al menos uno de los análisis de subgrupos. Sin embargo, en muchos casos la inconsistencia se valoró como grave o muy grave. Para ocho de los resultados incluidos en la comparación primaria se encontró heterogeneidad muy alta en los cálculos del efecto (I² > 80%) y heterogeneidad que en general no fue bien explicada por cualquiera de las características pronósticas incluidas en los análisis de subgrupos.
Falta de direccionalidad
En general, los resultados evaluados en estos estudios y las medidas utilizadas para evaluarlos parecen estar bien representados en la pregunta PICO, por lo que la calidad de la evidencia no se disminuyó por falta de direccionalidad para cualquiera de los resultados evaluados. Aunque las medidas de cognición y las puntuaciones de la prueba cognitiva no se corresponden directamente con la calidad de la realización de las actividades cotidianas, las puntuaciones cognitivas basadas en la evaluación psicométrica se consideran un verdadero reflejo de las capacidades cognitivas objetivas. De manera similar, en la medición del estado clínico de la enfermedad, la mayoría de los estudios que informaron este resultado lo hicieron a través de medidas de clasificación clínica ampliamente utilizadas, como la escala Clinical Dementia Rating (p.ej. Mapelli 2013) o la Rapid Disability Rating Scale (p.ej. Quintana Hernandez 2014), mientras que ninguno de los estudios incluidos utilizó indicaciones posiblemente más directas de la progresión clínica como el ingreso en una residencia geriátrica. A diferencia de los cambios en el estado de ánimo, la cognición o los síntomas conductuales, la progresión clínica de la enfermedad es un resultado a más largo plazo, en el contexto de la demencia leve en particular, y la evaluación de este resultado requiere de ensayos grandes con un poder estadístico adecuado que proporcionen un seguimiento a largo plazo.
Imprecisión
Para la comparación primaria (EC versus control al final del tratamiento), no hubo inquietudes importantes relacionadas con la imprecisión para el cálculo del efecto del resultado primario, a saber, la cognición global. Sin embargo, hubo inquietudes graves o muy graves en cuanto a la imprecisión con respecto a la mayoría de los resultados secundarios, incluidos todos los resultados no cognitivos y varios dominios cognitivos específicos. Estas inquietudes se debieron principalmente a los intervalos de confianza amplios en los cálculos del efecto, que incluyeron efectos potencialmente significativos, ningún efecto y efectos que favorecieron a la condición control. En las comparaciones adicionales (EC versus control a medio plazo y EC versus tratamiento alternativo al final del tratamiento y a medio plazo), se encontró que la imprecisión fue una inquietud grave o muy grave con relación a todos los resultados, incluido el resultado primario de progresión clínica a medio plazo. Para estas comparaciones adicionales, la imprecisión fue una inquietud debido al número mucho más pequeño de participantes en el que se basaron muchos de los cálculos del efecto, así como a los intervalos de confianza amplios de estos cálculos. Por lo tanto, con relación a muchos de los resultados de interés, se encontró que los estudios primarios difirieron en ocasiones no solo en cuanto al tamaño, sino también a la dirección de los efectos del EC.
Sesgo de publicación
Los resultados de la búsqueda indicaron que es posible que nunca se hayan publicado varios ensayos registrados en años recientes ni intervenciones realizadas como parte de proyectos de investigación de estudiantes, lo que plantea cierta inquietud acerca del sesgo de publicación positiva. Sin embargo, con la excepción de unos pocos resultados (p.ej. cambio en la memoria inmediata y retardada, fluidez de la letra verbal, función ejecutiva al final del tratamiento), no fue posible evaluar con suficiente confianza la presencia de sesgo de publicación mediante la inspección visual de los gráficos en embudo para cada resultado. Además, la asimetría en los gráficos en embudo puede ser causada por factores diferentes del sesgo de publicación, por lo que se decidió seguir un enfoque conservador; la calidad de la evidencia por un presunto sesgo de publicación solo se disminuyó en los casos en los que la asimetría en el gráfico en embudo (funnel plot) fue razonablemente evidente, y un mínimo de diez estudios habían evaluado el resultado relevante. Este enfoque puede haber dado lugar a una subestimación del grado real de inquietud relacionada con la presencia del sesgo de publicación.
Sesgos potenciales en el proceso de revisión
Dos autores de la revisión, de manera independiente, realizaron una búsqueda minuciosa de los artículos y un procedimiento riguroso de cribado y evaluación del riesgo de sesgo, y un tercer revisor resolvió los desacuerdos. De manera similar, la clasificación de la evidencia también la realizaron dos de los autores de revisión, que resolvieron los desacuerdos mediante discusión hasta que se alcanzó el consenso. El equipo de revisión incluye investigadores en todos los estadios de su carrera profesional y con diversos niveles de pericia específica en demencia, lo que reduce de manera adicional la probabilidad de sesgo sistemático en el proceso de revisión. En ninguno de los estudios incluidos participó alguno de los autores de la revisión, y no se han identificado conflictos de interés. Aunque es poco probable, no es posible descartar la posibilidad de que las dificultades asociadas con la valoración exacta con respecto a algunas áreas de posible sesgo hayan dado lugar a una sobrestimación (p.ej. riesgo de sesgo de selección debido a la falta de ocultación de la asignación) o subestimación (p.ej. sesgo de publicación) sistemáticas del riesgo real de sesgo.
Acuerdos y desacuerdos con otros estudios o revisiones
En años recientes se han realizado numerosas revisiones sistemáticas con y sin metanálisis de los tratamientos dirigidos a la cognición para los pacientes de edad avanzada con y sin demencia, y recientemente se ha examinado este amplio conjunto de trabajos (Malmberg Gavelin). Varias revisiones recientes centradas en el EC para los pacientes con demencia tienen una relevancia particular para la revisión actual, incluidas Alves 2013, Bahar‐Fuchs 2013, Huntley 2015, Folkerts 2017, y Hill 2017. Alves y colegas realizaron una revisión sistemática con metanálisis de cuatro estudios que cumplieron sus criterios de inclusión (tres de estos estudios se incluyeron en la presente revisión; Cahn‐Weiner 2003 Davis 2001 Heiss 1993). Un examen más cuidadoso indicó que el cuarto estudio incluido en esa revisión fue de tratamiento de estimulación cognitiva, por lo que no cumpliría los criterios para la revisión actual. Alves encontró que la intervención fue beneficiosa, en comparación con una intervención control, solo con respecto a la cognición global al final del tratamiento, como reflejó el Mini Mental State Examination (MMSE). Aunque el efecto fue grande, el metanálisis se basó en solo tres estudios (uno de los cuales fue el estudio de estimulación cognitiva) y 104 participantes, por lo que la precisión fue probablemente baja. Los otros cálculos se basaron en general en uno o dos estudios solamente, de manera que las conclusiones fueron naturalmente muy limitadas. Más recientemente, la revisión sistemática Huntley 2015 realizó un metanálisis de los ensayos de tratamiento dirigidos a la cognición para los pacientes con demencia y proporcionó cálculos separados del efecto para la cognición global de cuatro estudios clasificados como EC (todos se incluyeron en la presente revisión) y siete estudios clasificados como EC y estimulación combinados (tres se incluyeron en la revisión actual y se codificaron como "EC ampliado"). Sobre la base de tres estudios, los autores de la revisión no encontraron evidencia sólida de un efecto del EC en relación con una condición control activa sobre la cognición global, como refleja el MMSE (diferencia de medias estandarizada [DME] 0,22; intervalo de confianza [IC] del 95%: ‐0,74 a 1,18). Los hallazgos tampoco indicaron un beneficio del EC y la estimulación combinados sobre la cognición global, ya sea en comparación con un tratamiento control pasivo (DME 0,44; IC del 95%: ‐0,56 a 1,46) o con un tratamiento control activo (DME 0,25; IC del 95%: ‐0,18 a 0,68). Por otra parte, en la revisión actual el cambio en la cognición global reflejado por una puntuación compuesta y sobre la base de una medida de cribado (como el MMSE) fue mayor al final del tratamiento en el grupo de EC con respecto a la condición control según 20 estudios, y los cálculos del efecto fueron similares en cuanto a la magnitud cuando se contrastaron directamente las condiciones control activa (k = 8; DME 0,61) y pasiva (k = 12; DME 0,69). Es interesante señalar que los resultados de la revisión actual muestran una tendencia que indica que, aunque el tratamiento con EC "tradicional" (k = 13) se asocia con un efecto grande en relación con el tratamiento control (DME 0,83; IC del 95%: 0,30 a 1,39), el EC "ampliado" (k = 7) se asocia con un cálculo del efecto relativamente pequeño (DME 0,25; IC del 95%: ‐0,21 a 0,70) y las diferencias entre los dos subgrupos se acercaron a la significación (ji² = 2,68; gl = 1; p = 0,10). Folkerts 2017 informó recientemente una revisión sistemática con metanálisis de los tratamientos dirigidos a la cognición para los pacientes con demencia que viven en una residencia geriátrica; seis ensayos se clasificaron como EC, dos de los cuales contribuyeron al metanálisis (ambos estudios ‐ Kawashima 2005; Mapelli 2013 ‐ se incluyen en la presente revisión). Sobre la base de estos dos estudios con 47 participantes, estos autores encontraron que el EC fue superior al tratamiento control pasivo con respecto a la cognición global (DME 1,16; IC del 95%: 0,52 a 1,79), un hallazgo que es probable que sea muy impreciso debido al número pequeño de participantes en el que se basa, pero que, no obstante, coincide con los hallazgos de la presente revisión. Finalmente, Hill 2017, una revisión sistemática integral, realizó un metanálisis del EC computarizado para los pacientes con deficiencia cognitiva leve (DCL) y demencia e informó los efectos por separado para cada población. Sobre la base de un metanálisis de 12 estudios con un total de 389 participantes, esta revisión encontró un efecto pequeño del EC, en comparación con un tratamiento control, sobre la cognición global al final del tratamiento (DME 0,26; IC del 95%: 0,01 a 0,52), pero no encontró un efecto en otros dominios cognitivos.
Study flow diagram.
Risk of bias graph: review authors' judgements about each risk of bias item presented as percentages across all included studies.
Risk of bias summary: review authors' judgements about each risk of bias item for each included study.
Forest plot of comparison: 1 Cognitive training vs control immediately post intervention, outcome: 1.1 Change in a global measure of cognition (composite).
Funnel plot of comparison: 1 Cognitive training vs control immediately post intervention, outcome: 1.1 Change in a global measure of cognition (composite).
Forest plot of comparison: 3 Cognitive training vs alternative treatment immediately post intervention, outcome: 3.1 Change in a global measure of cognition (composite).
Forest plot of comparison: 1 Cognitive training vs control immediately post intervention, outcome: 1.3 Change in a global measure of cognition.
Forest plot of comparison: 2 Cognitive training vs control in the medium term (3 to 12 months post intervention), outcome: 2.5 Change in disease progression.
Forest plot of comparison: 1 Cognitive training vs control immediately post intervention, outcome: 1.6 Change in delayed memory.
Forest plot of comparison: 6 Cognitive training vs control immediately post intervention ‐ intervention dose, outcome: 6.9 Change in verbal letter fluency.
Forest plot of comparison: 9 Cognitive training vs control immediately post intervention ‐ type of CT (multi‐domain vs single domain), outcome: 9.12 Change in verbal category fluency.
Forest plot of comparison: 1 Cognitive training vs control immediately post intervention, outcome: 1.16 Change in participants' mood.
Forest plot of comparison: 1 Cognitive training vs control immediately post intervention, outcome: 1.17 Change in capacity for activities of daily living.
Forest plot of comparison: 1 Cognitive training vs control immediately post intervention, outcome: 1.20 Participant burden (retention rates).
Forest plot of comparison: 1 Cognitive training vs control immediately post intervention, outcome: 1.23 Change in mood and well‐being (CAREGIVER).
Comparison 1 Cognitive training vs control immediately post intervention, Outcome 1 Change in a global measure of cognition (composite).
Comparison 1 Cognitive training vs control immediately post intervention, Outcome 2 Change in a global measure of cognition (composite)_zero correlation.
Comparison 1 Cognitive training vs control immediately post intervention, Outcome 3 Change in a global measure of cognition.
Comparison 1 Cognitive training vs control immediately post intervention, Outcome 4 Change in a global measure of cognition_zero correlation.
Comparison 1 Cognitive training vs control immediately post intervention, Outcome 5 Change in disease progression.
Comparison 1 Cognitive training vs control immediately post intervention, Outcome 6 Change in delayed memory.
Comparison 1 Cognitive training vs control immediately post intervention, Outcome 7 Change in immediate memory.
Comparison 1 Cognitive training vs control immediately post intervention, Outcome 8 Change in attention and working memory.
Comparison 1 Cognitive training vs control immediately post intervention, Outcome 9 Change in language (naming).
Comparison 1 Cognitive training vs control immediately post intervention, Outcome 10 Change in verbal letter fluency.
Comparison 1 Cognitive training vs control immediately post intervention, Outcome 11 Change in verbal category fluency.
Comparison 1 Cognitive training vs control immediately post intervention, Outcome 12 Change in executive function.
Comparison 1 Cognitive training vs control immediately post intervention, Outcome 13 Change in speed of information processing.
Comparison 1 Cognitive training vs control immediately post intervention, Outcome 14 Change in meta cognition (self‐reported).
Comparison 1 Cognitive training vs control immediately post intervention, Outcome 15 Change in meta cognition (informant‐reported).
Comparison 1 Cognitive training vs control immediately post intervention, Outcome 16 Change in participants' mood.
Comparison 1 Cognitive training vs control immediately post intervention, Outcome 17 Change in capacity for activities of daily living.
Comparison 1 Cognitive training vs control immediately post intervention, Outcome 18 Change in general health and quality of life.
Comparison 1 Cognitive training vs control immediately post intervention, Outcome 19 Change in behavioural and psychological symptoms of dementia (BPSD).
Comparison 1 Cognitive training vs control immediately post intervention, Outcome 20 Participant burden (retention rates).
Comparison 1 Cognitive training vs control immediately post intervention, Outcome 21 Change in burden of care (CAREGIVER).
Comparison 1 Cognitive training vs control immediately post intervention, Outcome 22 Change in quality of life (CAREGIVER).
Comparison 1 Cognitive training vs control immediately post intervention, Outcome 23 Change in mood and well‐being (CAREGIVER).
Comparison 2 Cognitive training vs control in the medium term (3 to 12 months post intervention), Outcome 1 Change in a global measure of cognition (composite).
Comparison 2 Cognitive training vs control in the medium term (3 to 12 months post intervention), Outcome 2 Change in a global measure of cognition (composite)_zero correlation.
Comparison 2 Cognitive training vs control in the medium term (3 to 12 months post intervention), Outcome 3 Change in a global measure of cognition.
Comparison 2 Cognitive training vs control in the medium term (3 to 12 months post intervention), Outcome 4 Change in a global measure of cognition (zero correlation).
Comparison 2 Cognitive training vs control in the medium term (3 to 12 months post intervention), Outcome 5 Change in disease progression.
Comparison 2 Cognitive training vs control in the medium term (3 to 12 months post intervention), Outcome 6 Change in disease progression (zero correlation).
Comparison 2 Cognitive training vs control in the medium term (3 to 12 months post intervention), Outcome 7 Change in delayed memory.
Comparison 2 Cognitive training vs control in the medium term (3 to 12 months post intervention), Outcome 8 Change in immediate memory.
Comparison 2 Cognitive training vs control in the medium term (3 to 12 months post intervention), Outcome 9 Change in attention and working memory.
Comparison 2 Cognitive training vs control in the medium term (3 to 12 months post intervention), Outcome 10 Change in language (naming).
Comparison 2 Cognitive training vs control in the medium term (3 to 12 months post intervention), Outcome 11 Change in verbal letter fluency.
Comparison 2 Cognitive training vs control in the medium term (3 to 12 months post intervention), Outcome 12 Change in verbal category fluency.
Comparison 2 Cognitive training vs control in the medium term (3 to 12 months post intervention), Outcome 13 Change in executive function.
Comparison 2 Cognitive training vs control in the medium term (3 to 12 months post intervention), Outcome 14 Change in speed of information processing.
Comparison 2 Cognitive training vs control in the medium term (3 to 12 months post intervention), Outcome 15 Change in meta cognition (self‐reported).
Comparison 2 Cognitive training vs control in the medium term (3 to 12 months post intervention), Outcome 16 Change in meta cognition (informant‐reported).
Comparison 2 Cognitive training vs control in the medium term (3 to 12 months post intervention), Outcome 17 Change in participants' mood.
Comparison 2 Cognitive training vs control in the medium term (3 to 12 months post intervention), Outcome 18 Change in capacity for activities of daily living.
Comparison 2 Cognitive training vs control in the medium term (3 to 12 months post intervention), Outcome 19 Change in general health and quality of life.
Comparison 2 Cognitive training vs control in the medium term (3 to 12 months post intervention), Outcome 20 Change in behavioural and psychological symptoms of dementia (BPSD).
Comparison 3 Cognitive training vs alternative treatment immediately post intervention, Outcome 1 Change in a global measure of cognition (composite).
Comparison 3 Cognitive training vs alternative treatment immediately post intervention, Outcome 2 Change in a global measure of cognition (composite)_zero correlation.
Comparison 3 Cognitive training vs alternative treatment immediately post intervention, Outcome 3 Change in a global measure of cognition.
Comparison 3 Cognitive training vs alternative treatment immediately post intervention, Outcome 4 Change in a global measure of cognition_zero correlation.
Comparison 3 Cognitive training vs alternative treatment immediately post intervention, Outcome 5 Change in disease progression.
Comparison 3 Cognitive training vs alternative treatment immediately post intervention, Outcome 6 Change in delayed memory.
Comparison 3 Cognitive training vs alternative treatment immediately post intervention, Outcome 7 Change in immediate memory.
Comparison 3 Cognitive training vs alternative treatment immediately post intervention, Outcome 8 Change in attention and working memory.
Comparison 3 Cognitive training vs alternative treatment immediately post intervention, Outcome 9 Change in language (naming).
Comparison 3 Cognitive training vs alternative treatment immediately post intervention, Outcome 10 Change in verbal letter fluency.
Comparison 3 Cognitive training vs alternative treatment immediately post intervention, Outcome 11 Change in verbal category fluency.
Comparison 3 Cognitive training vs alternative treatment immediately post intervention, Outcome 12 Change in executive function.
Comparison 3 Cognitive training vs alternative treatment immediately post intervention, Outcome 13 Change in speed of information processing.
Comparison 3 Cognitive training vs alternative treatment immediately post intervention, Outcome 16 Change in participants' mood.
Comparison 3 Cognitive training vs alternative treatment immediately post intervention, Outcome 17 Change in capacity for activities of daily living.
Comparison 3 Cognitive training vs alternative treatment immediately post intervention, Outcome 18 Change in general health and quality of life.
Comparison 3 Cognitive training vs alternative treatment immediately post intervention, Outcome 19 Change in behavioural and psychological symptoms of dementia (BPSD).
Comparison 3 Cognitive training vs alternative treatment immediately post intervention, Outcome 20 Participant burden (retention rates).
Comparison 3 Cognitive training vs alternative treatment immediately post intervention, Outcome 21 Change in burden of care (CAREGIVER).
Comparison 3 Cognitive training vs alternative treatment immediately post intervention, Outcome 22 Change in quality of life (CAREGIVER).
Comparison 3 Cognitive training vs alternative treatment immediately post intervention, Outcome 23 Change in mood and well‐being (CAREGIVER).
Comparison 4 Cognitive training vs alternative treatment in the medium term (3 to 12 months post intervention), Outcome 1 Change in a global measure of cognition (composite).
Comparison 4 Cognitive training vs alternative treatment in the medium term (3 to 12 months post intervention), Outcome 2 Change in a global measure of cognition (composite)_zero correlation.
Comparison 4 Cognitive training vs alternative treatment in the medium term (3 to 12 months post intervention), Outcome 3 Change in a global measure of cognition.
Comparison 4 Cognitive training vs alternative treatment in the medium term (3 to 12 months post intervention), Outcome 6 Change in delayed memory.
Comparison 4 Cognitive training vs alternative treatment in the medium term (3 to 12 months post intervention), Outcome 7 Change in immediate memory.
Comparison 4 Cognitive training vs alternative treatment in the medium term (3 to 12 months post intervention), Outcome 8 Change in attention and working memory.
Comparison 4 Cognitive training vs alternative treatment in the medium term (3 to 12 months post intervention), Outcome 9 Change in language (naming).
Comparison 4 Cognitive training vs alternative treatment in the medium term (3 to 12 months post intervention), Outcome 10 Change in verbal letter fluency.
Comparison 4 Cognitive training vs alternative treatment in the medium term (3 to 12 months post intervention), Outcome 11 Change in verbal category fluency.
Comparison 4 Cognitive training vs alternative treatment in the medium term (3 to 12 months post intervention), Outcome 12 Change in executive function.
Comparison 4 Cognitive training vs alternative treatment in the medium term (3 to 12 months post intervention), Outcome 13 Change in speed of information processing.
Comparison 4 Cognitive training vs alternative treatment in the medium term (3 to 12 months post intervention), Outcome 16 Change in participants' mood.
Comparison 4 Cognitive training vs alternative treatment in the medium term (3 to 12 months post intervention), Outcome 18 Change in general health and quality of life.
Comparison 5 Cognitive training vs control immediately post intervention ‐ risk of bias, Outcome 1 Change in a global measure of cognition.
Comparison 5 Cognitive training vs control immediately post intervention ‐ risk of bias, Outcome 2 Change in a global measure of cognition_zero correlation.
Comparison 5 Cognitive training vs control immediately post intervention ‐ risk of bias, Outcome 3 Change in a global measure of cognition (composite).
Comparison 5 Cognitive training vs control immediately post intervention ‐ risk of bias, Outcome 4 Change in a global measure of cognition (composite)_zero correlation.
Comparison 5 Cognitive training vs control immediately post intervention ‐ risk of bias, Outcome 5 Change in immediate memory.
Comparison 5 Cognitive training vs control immediately post intervention ‐ risk of bias, Outcome 6 Change in delayed memory.
Comparison 5 Cognitive training vs control immediately post intervention ‐ risk of bias, Outcome 7 Change in attention and working memory.
Comparison 5 Cognitive training vs control immediately post intervention ‐ risk of bias, Outcome 8 Change in language (naming).
Comparison 5 Cognitive training vs control immediately post intervention ‐ risk of bias, Outcome 9 Change in verbal letter fluency.
Comparison 5 Cognitive training vs control immediately post intervention ‐ risk of bias, Outcome 10 Change in speed of information processing.
Comparison 5 Cognitive training vs control immediately post intervention ‐ risk of bias, Outcome 11 Change in executive function.
Comparison 5 Cognitive training vs control immediately post intervention ‐ risk of bias, Outcome 12 Change in verbal category fluency.
Comparison 5 Cognitive training vs control immediately post intervention ‐ risk of bias, Outcome 13 Change in meta cognition (self‐reported).
Comparison 5 Cognitive training vs control immediately post intervention ‐ risk of bias, Outcome 14 Change in meta cognition (informant‐reported).
Comparison 5 Cognitive training vs control immediately post intervention ‐ risk of bias, Outcome 15 Change in participants' mood.
Comparison 5 Cognitive training vs control immediately post intervention ‐ risk of bias, Outcome 16 Change in capacity for activities of daily living.
Comparison 5 Cognitive training vs control immediately post intervention ‐ risk of bias, Outcome 17 Change in general health and quality of life.
Comparison 5 Cognitive training vs control immediately post intervention ‐ risk of bias, Outcome 18 Change in behavioural and psychological symptoms of dementia (BPSD).
Comparison 5 Cognitive training vs control immediately post intervention ‐ risk of bias, Outcome 19 Change in disease progression.
Comparison 5 Cognitive training vs control immediately post intervention ‐ risk of bias, Outcome 20 Change in burden of care (CAREGIVER).
Comparison 5 Cognitive training vs control immediately post intervention ‐ risk of bias, Outcome 21 Change in quality of life (CAREGIVER).
Comparison 5 Cognitive training vs control immediately post intervention ‐ risk of bias, Outcome 22 Change in mood and well‐being (CAREGIVER).
Comparison 5 Cognitive training vs control immediately post intervention ‐ risk of bias, Outcome 23 Participant burden (retention rates).
Comparison 5 Cognitive training vs control immediately post intervention ‐ risk of bias, Outcome 24 Change in general health and quality of life.
Comparison 6 Cognitive training vs control immediately post intervention ‐ intervention dose, Outcome 1 Change in a global measure of cognition.
Comparison 6 Cognitive training vs control immediately post intervention ‐ intervention dose, Outcome 2 Change in a global measure of cognition_zero correlation.
Comparison 6 Cognitive training vs control immediately post intervention ‐ intervention dose, Outcome 3 Change in a global measure of cognition (composite).
Comparison 6 Cognitive training vs control immediately post intervention ‐ intervention dose, Outcome 4 Change in a global measure of cognition (composite)_zero correlation.
Comparison 6 Cognitive training vs control immediately post intervention ‐ intervention dose, Outcome 5 Change in immediate memory.
Comparison 6 Cognitive training vs control immediately post intervention ‐ intervention dose, Outcome 6 Change in delayed memory.
Comparison 6 Cognitive training vs control immediately post intervention ‐ intervention dose, Outcome 7 Change in attention and working memory.
Comparison 6 Cognitive training vs control immediately post intervention ‐ intervention dose, Outcome 8 Change in language (naming).
Comparison 6 Cognitive training vs control immediately post intervention ‐ intervention dose, Outcome 9 Change in verbal letter fluency.
Comparison 6 Cognitive training vs control immediately post intervention ‐ intervention dose, Outcome 10 Change in speed of information processing.
Comparison 6 Cognitive training vs control immediately post intervention ‐ intervention dose, Outcome 11 Change in executive function.
Comparison 6 Cognitive training vs control immediately post intervention ‐ intervention dose, Outcome 12 Change in verbal category fluency.
Comparison 6 Cognitive training vs control immediately post intervention ‐ intervention dose, Outcome 13 Change in meta cognition (self‐reported).
Comparison 6 Cognitive training vs control immediately post intervention ‐ intervention dose, Outcome 14 Change in meta cognition (informant‐reported).
Comparison 6 Cognitive training vs control immediately post intervention ‐ intervention dose, Outcome 15 Change in participants' mood.
Comparison 6 Cognitive training vs control immediately post intervention ‐ intervention dose, Outcome 16 Change in capacity for activities of daily living.
Comparison 6 Cognitive training vs control immediately post intervention ‐ intervention dose, Outcome 17 Change in disease progression.
Comparison 6 Cognitive training vs control immediately post intervention ‐ intervention dose, Outcome 18 Change in behavioural and psychological symptoms of dementia (BPSD).
Comparison 6 Cognitive training vs control immediately post intervention ‐ intervention dose, Outcome 19 Change in attention and working memory.
Comparison 6 Cognitive training vs control immediately post intervention ‐ intervention dose, Outcome 20 Change in burden of care (CAREGIVER).
Comparison 6 Cognitive training vs control immediately post intervention ‐ intervention dose, Outcome 21 Change in quality of life (CAREGIVER).
Comparison 6 Cognitive training vs control immediately post intervention ‐ intervention dose, Outcome 22 Change in mood and well‐being (CAREGIVER).
Comparison 6 Cognitive training vs control immediately post intervention ‐ intervention dose, Outcome 23 Participant burden (retention rates).
Comparison 6 Cognitive training vs control immediately post intervention ‐ intervention dose, Outcome 24 Change in general health and quality of life.
Comparison 7 Cognitive training vs control immediately post intervention ‐ intervention duration, Outcome 1 Change in a global measure of cognition.
Comparison 7 Cognitive training vs control immediately post intervention ‐ intervention duration, Outcome 2 Change in a global measure of cognition_zero correlation.
Comparison 7 Cognitive training vs control immediately post intervention ‐ intervention duration, Outcome 3 Change in a global measure of cognition (composite).
Comparison 7 Cognitive training vs control immediately post intervention ‐ intervention duration, Outcome 4 Change in a global measure of cognition (composite)_zero correlation.
Comparison 7 Cognitive training vs control immediately post intervention ‐ intervention duration, Outcome 5 Change in immediate memory.
Comparison 7 Cognitive training vs control immediately post intervention ‐ intervention duration, Outcome 6 Change in delayed memory.
Comparison 7 Cognitive training vs control immediately post intervention ‐ intervention duration, Outcome 7 Change in attention and working memory.
Comparison 7 Cognitive training vs control immediately post intervention ‐ intervention duration, Outcome 8 Change in language (naming).
Comparison 7 Cognitive training vs control immediately post intervention ‐ intervention duration, Outcome 9 Change in verbal letter fluency.
Comparison 7 Cognitive training vs control immediately post intervention ‐ intervention duration, Outcome 10 Change in speed of information processing.
Comparison 7 Cognitive training vs control immediately post intervention ‐ intervention duration, Outcome 11 Change in executive function.
Comparison 7 Cognitive training vs control immediately post intervention ‐ intervention duration, Outcome 12 Change in verbal category fluency.
Comparison 7 Cognitive training vs control immediately post intervention ‐ intervention duration, Outcome 13 Change in meta cognition (self‐reported).
Comparison 7 Cognitive training vs control immediately post intervention ‐ intervention duration, Outcome 14 Change in meta cognition (informant‐reported).
Comparison 7 Cognitive training vs control immediately post intervention ‐ intervention duration, Outcome 15 Change in participants' mood.
Comparison 7 Cognitive training vs control immediately post intervention ‐ intervention duration, Outcome 16 Change in capacity for activities of daily living.
Comparison 7 Cognitive training vs control immediately post intervention ‐ intervention duration, Outcome 17 Change in disease progression.
Comparison 7 Cognitive training vs control immediately post intervention ‐ intervention duration, Outcome 18 Change in behavioural and psychological symptoms of dementia (BPSD).
Comparison 7 Cognitive training vs control immediately post intervention ‐ intervention duration, Outcome 19 Participant burden (retention rates).
Comparison 7 Cognitive training vs control immediately post intervention ‐ intervention duration, Outcome 20 Change in burden of care (CAREGIVER).
Comparison 7 Cognitive training vs control immediately post intervention ‐ intervention duration, Outcome 21 Change in quality of life (CAREGIVER).
Comparison 7 Cognitive training vs control immediately post intervention ‐ intervention duration, Outcome 22 Change in mood and well‐being (CAREGIVER).
Comparison 7 Cognitive training vs control immediately post intervention ‐ intervention duration, Outcome 23 Change in general health and quality of life.
Comparison 8 Cognitive training vs control immediately post intervention ‐ type of CT (traditional vs augmented), Outcome 1 Change in a global measure of cognition.
Comparison 8 Cognitive training vs control immediately post intervention ‐ type of CT (traditional vs augmented), Outcome 2 Change in a global measure of cognition_zero correlation.
Comparison 8 Cognitive training vs control immediately post intervention ‐ type of CT (traditional vs augmented), Outcome 3 Change in a global measure of cognition (composite).
Comparison 8 Cognitive training vs control immediately post intervention ‐ type of CT (traditional vs augmented), Outcome 4 Change in a global measure of cognition (composite)_zero correlation.
Comparison 8 Cognitive training vs control immediately post intervention ‐ type of CT (traditional vs augmented), Outcome 5 Change in immediate memory.
Comparison 8 Cognitive training vs control immediately post intervention ‐ type of CT (traditional vs augmented), Outcome 6 Change in delayed memory.
Comparison 8 Cognitive training vs control immediately post intervention ‐ type of CT (traditional vs augmented), Outcome 7 Change in attention and working memory.
Comparison 8 Cognitive training vs control immediately post intervention ‐ type of CT (traditional vs augmented), Outcome 8 Change in language (naming).
Comparison 8 Cognitive training vs control immediately post intervention ‐ type of CT (traditional vs augmented), Outcome 9 Change in verbal letter fluency.
Comparison 8 Cognitive training vs control immediately post intervention ‐ type of CT (traditional vs augmented), Outcome 10 Change in speed of information processing.
Comparison 8 Cognitive training vs control immediately post intervention ‐ type of CT (traditional vs augmented), Outcome 11 Change in executive function.
Comparison 8 Cognitive training vs control immediately post intervention ‐ type of CT (traditional vs augmented), Outcome 12 Change in verbal category fluency.
Comparison 8 Cognitive training vs control immediately post intervention ‐ type of CT (traditional vs augmented), Outcome 13 Change in meta cognition (self‐reported).
Comparison 8 Cognitive training vs control immediately post intervention ‐ type of CT (traditional vs augmented), Outcome 14 Change in meta cognition (informant‐reported).
Comparison 8 Cognitive training vs control immediately post intervention ‐ type of CT (traditional vs augmented), Outcome 15 Change in participants' mood.
Comparison 8 Cognitive training vs control immediately post intervention ‐ type of CT (traditional vs augmented), Outcome 16 Change in capacity for activities of daily living.
Comparison 8 Cognitive training vs control immediately post intervention ‐ type of CT (traditional vs augmented), Outcome 17 Change in disease progression.
Comparison 8 Cognitive training vs control immediately post intervention ‐ type of CT (traditional vs augmented), Outcome 18 Change in behavioural and psychological symptoms of dementia (BPSD).
Comparison 8 Cognitive training vs control immediately post intervention ‐ type of CT (traditional vs augmented), Outcome 19 Participant burden (retention rates).
Comparison 8 Cognitive training vs control immediately post intervention ‐ type of CT (traditional vs augmented), Outcome 20 Change in burden of care (CAREGIVER).
Comparison 8 Cognitive training vs control immediately post intervention ‐ type of CT (traditional vs augmented), Outcome 21 Change in quality of life (CAREGIVER).
Comparison 8 Cognitive training vs control immediately post intervention ‐ type of CT (traditional vs augmented), Outcome 22 Change in mood and well‐being (CAREGIVER).
Comparison 8 Cognitive training vs control immediately post intervention ‐ type of CT (traditional vs augmented), Outcome 23 Change in general health and quality of life.
Comparison 9 Cognitive training vs control immediately post intervention ‐ type of CT (multi‐domain vs single domain), Outcome 1 Change in a global measure of cognition.
Comparison 9 Cognitive training vs control immediately post intervention ‐ type of CT (multi‐domain vs single domain), Outcome 2 Change in a global measure of cognition_zero correlation.
Comparison 9 Cognitive training vs control immediately post intervention ‐ type of CT (multi‐domain vs single domain), Outcome 3 Change in a global measure of cognition (composite).
Comparison 9 Cognitive training vs control immediately post intervention ‐ type of CT (multi‐domain vs single domain), Outcome 4 Change in a global measure of cognition (composite)_zero correlation.
Comparison 9 Cognitive training vs control immediately post intervention ‐ type of CT (multi‐domain vs single domain), Outcome 5 Change in immediate memory.
Comparison 9 Cognitive training vs control immediately post intervention ‐ type of CT (multi‐domain vs single domain), Outcome 6 Change in delayed memory.
Comparison 9 Cognitive training vs control immediately post intervention ‐ type of CT (multi‐domain vs single domain), Outcome 7 Change in attention and working memory.
Comparison 9 Cognitive training vs control immediately post intervention ‐ type of CT (multi‐domain vs single domain), Outcome 8 Change in language (naming).
Comparison 9 Cognitive training vs control immediately post intervention ‐ type of CT (multi‐domain vs single domain), Outcome 9 Change in verbal letter fluency.
Comparison 9 Cognitive training vs control immediately post intervention ‐ type of CT (multi‐domain vs single domain), Outcome 10 Change in speed of information processing.
Comparison 9 Cognitive training vs control immediately post intervention ‐ type of CT (multi‐domain vs single domain), Outcome 11 Change in executive function.
Comparison 9 Cognitive training vs control immediately post intervention ‐ type of CT (multi‐domain vs single domain), Outcome 12 Change in verbal category fluency.
Comparison 9 Cognitive training vs control immediately post intervention ‐ type of CT (multi‐domain vs single domain), Outcome 13 Change in meta cognition (self‐reported).
Comparison 9 Cognitive training vs control immediately post intervention ‐ type of CT (multi‐domain vs single domain), Outcome 14 Change in meta cognition (informant‐reported).
Comparison 9 Cognitive training vs control immediately post intervention ‐ type of CT (multi‐domain vs single domain), Outcome 15 Change in participants' mood.
Comparison 9 Cognitive training vs control immediately post intervention ‐ type of CT (multi‐domain vs single domain), Outcome 16 Change in capacity for activities of daily living.
Comparison 9 Cognitive training vs control immediately post intervention ‐ type of CT (multi‐domain vs single domain), Outcome 17 Change in disease progression.
Comparison 9 Cognitive training vs control immediately post intervention ‐ type of CT (multi‐domain vs single domain), Outcome 18 Change in behavioural and psychological symptoms of dementia (BPSD).
Comparison 9 Cognitive training vs control immediately post intervention ‐ type of CT (multi‐domain vs single domain), Outcome 19 Participant burden (retention rates).
Comparison 9 Cognitive training vs control immediately post intervention ‐ type of CT (multi‐domain vs single domain), Outcome 20 Change in burden of care (CAREGIVER).
Comparison 9 Cognitive training vs control immediately post intervention ‐ type of CT (multi‐domain vs single domain), Outcome 21 Change in quality of life (CAREGIVER).
Comparison 9 Cognitive training vs control immediately post intervention ‐ type of CT (multi‐domain vs single domain), Outcome 22 Change in mood and well‐being (CAREGIVER).
Comparison 9 Cognitive training vs control immediately post intervention ‐ type of CT (multi‐domain vs single domain), Outcome 23 Change in general health and quality of life.
Comparison 10 Cognitive training vs control immediately post intervention ‐ type of control (passive vs active), Outcome 1 Change in a global measure of cognition.
Comparison 10 Cognitive training vs control immediately post intervention ‐ type of control (passive vs active), Outcome 2 Change in a global measure of cognition_zero correlation.
Comparison 10 Cognitive training vs control immediately post intervention ‐ type of control (passive vs active), Outcome 3 Change in a global measure of cognition (composite).
Comparison 10 Cognitive training vs control immediately post intervention ‐ type of control (passive vs active), Outcome 4 Change in a global measure of cognition (composite)_zero correlation.
Comparison 10 Cognitive training vs control immediately post intervention ‐ type of control (passive vs active), Outcome 5 Change in immediate memory.
Comparison 10 Cognitive training vs control immediately post intervention ‐ type of control (passive vs active), Outcome 6 Change in delayed memory.
Comparison 10 Cognitive training vs control immediately post intervention ‐ type of control (passive vs active), Outcome 7 Change in attention and working memory.
Comparison 10 Cognitive training vs control immediately post intervention ‐ type of control (passive vs active), Outcome 8 Change in language (naming).
Comparison 10 Cognitive training vs control immediately post intervention ‐ type of control (passive vs active), Outcome 9 Change in verbal letter fluency.
Comparison 10 Cognitive training vs control immediately post intervention ‐ type of control (passive vs active), Outcome 10 Change in speed of information processing.
Comparison 10 Cognitive training vs control immediately post intervention ‐ type of control (passive vs active), Outcome 11 Change in executive function.
Comparison 10 Cognitive training vs control immediately post intervention ‐ type of control (passive vs active), Outcome 12 Change in verbal category fluency.
Comparison 10 Cognitive training vs control immediately post intervention ‐ type of control (passive vs active), Outcome 13 Change in meta cognition (self‐reported).
Comparison 10 Cognitive training vs control immediately post intervention ‐ type of control (passive vs active), Outcome 14 Change in meta cognition (informant‐reported).
Comparison 10 Cognitive training vs control immediately post intervention ‐ type of control (passive vs active), Outcome 15 Change in participants' mood.
Comparison 10 Cognitive training vs control immediately post intervention ‐ type of control (passive vs active), Outcome 16 Change in capacity for activities of daily living.
Comparison 10 Cognitive training vs control immediately post intervention ‐ type of control (passive vs active), Outcome 17 Change in disease progression.
Comparison 10 Cognitive training vs control immediately post intervention ‐ type of control (passive vs active), Outcome 18 Change in behavioural and psychological symptoms of dementia (BPSD).
Comparison 10 Cognitive training vs control immediately post intervention ‐ type of control (passive vs active), Outcome 19 Participant burden (retention rates).
Comparison 10 Cognitive training vs control immediately post intervention ‐ type of control (passive vs active), Outcome 20 Change in burden of care (CAREGIVER).
Comparison 10 Cognitive training vs control immediately post intervention ‐ type of control (passive vs active), Outcome 21 Change in quality of life (CAREGIVER).
Comparison 10 Cognitive training vs control immediately post intervention ‐ type of control (passive vs active), Outcome 22 Change in mood and well‐being (CAREGIVER).
Comparison 10 Cognitive training vs control immediately post intervention ‐ type of control (passive vs active), Outcome 23 Change in general health and quality of life.
Comparison 11 Cognitive training vs alternative treatment immediately post intervention ‐ intervention dose, Outcome 1 Change in a global measure of cognition.
Comparison 11 Cognitive training vs alternative treatment immediately post intervention ‐ intervention dose, Outcome 2 Change in a global measure of cognition_zero correlation.
Comparison 11 Cognitive training vs alternative treatment immediately post intervention ‐ intervention dose, Outcome 3 Change in a global measure of cognition (composite).
Comparison 11 Cognitive training vs alternative treatment immediately post intervention ‐ intervention dose, Outcome 4 Change in a global measure of cognition (composite)_zero correlation.
Comparison 11 Cognitive training vs alternative treatment immediately post intervention ‐ intervention dose, Outcome 5 Change in immediate memory.
Comparison 11 Cognitive training vs alternative treatment immediately post intervention ‐ intervention dose, Outcome 6 Change in delayed memory.
Comparison 11 Cognitive training vs alternative treatment immediately post intervention ‐ intervention dose, Outcome 7 Change in attention and working memory.
Comparison 11 Cognitive training vs alternative treatment immediately post intervention ‐ intervention dose, Outcome 8 Change in language (naming).
Comparison 11 Cognitive training vs alternative treatment immediately post intervention ‐ intervention dose, Outcome 9 Change in verbal letter fluency.
Comparison 11 Cognitive training vs alternative treatment immediately post intervention ‐ intervention dose, Outcome 10 Change in verbal category fluency.
Comparison 11 Cognitive training vs alternative treatment immediately post intervention ‐ intervention dose, Outcome 11 Change in executive function.
Comparison 11 Cognitive training vs alternative treatment immediately post intervention ‐ intervention dose, Outcome 14 Change in participants' mood.
Comparison 11 Cognitive training vs alternative treatment immediately post intervention ‐ intervention dose, Outcome 15 Change in capacity for activities of daily living.
Comparison 11 Cognitive training vs alternative treatment immediately post intervention ‐ intervention dose, Outcome 16 Change in behavioural and psychological symptoms of dementia (BPSD).
Comparison 11 Cognitive training vs alternative treatment immediately post intervention ‐ intervention dose, Outcome 17 Change in disease progression.
Comparison 11 Cognitive training vs alternative treatment immediately post intervention ‐ intervention dose, Outcome 18 Participant burden (retention rates).
Comparison 11 Cognitive training vs alternative treatment immediately post intervention ‐ intervention dose, Outcome 19 Change in mood and well‐being (CAREGIVER).
Comparison 11 Cognitive training vs alternative treatment immediately post intervention ‐ intervention dose, Outcome 20 Change in burden of care (CAREGIVER).
Comparison 11 Cognitive training vs alternative treatment immediately post intervention ‐ intervention dose, Outcome 21 Change in quality of life (CAREGIVER).
Comparison 11 Cognitive training vs alternative treatment immediately post intervention ‐ intervention dose, Outcome 22 Change in speed of information processing.
Comparison 11 Cognitive training vs alternative treatment immediately post intervention ‐ intervention dose, Outcome 23 Change in general health and quality of life.
Comparison 12 Cognitive training vs alternative treatment immediately post intervention ‐ type of CT (traditional vs augmented), Outcome 1 Change in a global measure of cognition.
Comparison 12 Cognitive training vs alternative treatment immediately post intervention ‐ type of CT (traditional vs augmented), Outcome 2 Change in a global measure of cognition_zero correlation.
Comparison 12 Cognitive training vs alternative treatment immediately post intervention ‐ type of CT (traditional vs augmented), Outcome 3 Change in a global measure of cognition (composite).
Comparison 12 Cognitive training vs alternative treatment immediately post intervention ‐ type of CT (traditional vs augmented), Outcome 4 Change in a global measure of cognition (composite)_zero correlation.
Comparison 12 Cognitive training vs alternative treatment immediately post intervention ‐ type of CT (traditional vs augmented), Outcome 5 Change in immediate memory.
Comparison 12 Cognitive training vs alternative treatment immediately post intervention ‐ type of CT (traditional vs augmented), Outcome 6 Change in delayed memory.
Comparison 12 Cognitive training vs alternative treatment immediately post intervention ‐ type of CT (traditional vs augmented), Outcome 7 Change in attention and working memory.
Comparison 12 Cognitive training vs alternative treatment immediately post intervention ‐ type of CT (traditional vs augmented), Outcome 8 Change in language (naming).
Comparison 12 Cognitive training vs alternative treatment immediately post intervention ‐ type of CT (traditional vs augmented), Outcome 9 Change in verbal letter fluency.
Comparison 12 Cognitive training vs alternative treatment immediately post intervention ‐ type of CT (traditional vs augmented), Outcome 10 Change in verbal category fluency.
Comparison 12 Cognitive training vs alternative treatment immediately post intervention ‐ type of CT (traditional vs augmented), Outcome 11 Change in executive function.
Comparison 12 Cognitive training vs alternative treatment immediately post intervention ‐ type of CT (traditional vs augmented), Outcome 14 Change in participants' mood.
Comparison 12 Cognitive training vs alternative treatment immediately post intervention ‐ type of CT (traditional vs augmented), Outcome 15 Change in capacity for activities of daily living.
Comparison 12 Cognitive training vs alternative treatment immediately post intervention ‐ type of CT (traditional vs augmented), Outcome 16 Change in behavioural and psychological symptoms of dementia (BPSD).
Comparison 12 Cognitive training vs alternative treatment immediately post intervention ‐ type of CT (traditional vs augmented), Outcome 17 Change in disease progression.
Comparison 12 Cognitive training vs alternative treatment immediately post intervention ‐ type of CT (traditional vs augmented), Outcome 18 Participant burden (retention rates).
Comparison 12 Cognitive training vs alternative treatment immediately post intervention ‐ type of CT (traditional vs augmented), Outcome 19 Change in mood and well‐being (CAREGIVER).
Comparison 12 Cognitive training vs alternative treatment immediately post intervention ‐ type of CT (traditional vs augmented), Outcome 20 Change in burden of care (CAREGIVER).
Comparison 12 Cognitive training vs alternative treatment immediately post intervention ‐ type of CT (traditional vs augmented), Outcome 21 Change in quality of life (CAREGIVER).
Comparison 12 Cognitive training vs alternative treatment immediately post intervention ‐ type of CT (traditional vs augmented), Outcome 22 Change in speed of information processing.
Comparison 12 Cognitive training vs alternative treatment immediately post intervention ‐ type of CT (traditional vs augmented), Outcome 23 Change in general health and quality of life.
Comparison 13 Cognitive training vs control in the medium term (3 to 12 months post intervention) ‐ follow‐up period, Outcome 1 Change in a global measure of cognition.
Comparison 13 Cognitive training vs control in the medium term (3 to 12 months post intervention) ‐ follow‐up period, Outcome 2 Change in a global measure of cognition (zero correlation).
Comparison 13 Cognitive training vs control in the medium term (3 to 12 months post intervention) ‐ follow‐up period, Outcome 3 Change in a global measure of cognition (composite).
Comparison 13 Cognitive training vs control in the medium term (3 to 12 months post intervention) ‐ follow‐up period, Outcome 4 Change in a global measure of cognition (composite)_zero correlation.
Comparison 13 Cognitive training vs control in the medium term (3 to 12 months post intervention) ‐ follow‐up period, Outcome 5 Change in disease progression (zero correlation).
Comparison 13 Cognitive training vs control in the medium term (3 to 12 months post intervention) ‐ follow‐up period, Outcome 6 Change in disease progression.
Comparison 13 Cognitive training vs control in the medium term (3 to 12 months post intervention) ‐ follow‐up period, Outcome 7 Change in immediate memory.
Comparison 13 Cognitive training vs control in the medium term (3 to 12 months post intervention) ‐ follow‐up period, Outcome 8 Change in delayed memory.
Comparison 13 Cognitive training vs control in the medium term (3 to 12 months post intervention) ‐ follow‐up period, Outcome 9 Change in language (naming).
Comparison 13 Cognitive training vs control in the medium term (3 to 12 months post intervention) ‐ follow‐up period, Outcome 10 Change in verbal letter fluency.
Comparison 13 Cognitive training vs control in the medium term (3 to 12 months post intervention) ‐ follow‐up period, Outcome 11 Change in verbal category fluency.
Comparison 13 Cognitive training vs control in the medium term (3 to 12 months post intervention) ‐ follow‐up period, Outcome 12 Change in attention and working memory.
Comparison 13 Cognitive training vs control in the medium term (3 to 12 months post intervention) ‐ follow‐up period, Outcome 13 Change in speed of information processing.
Comparison 13 Cognitive training vs control in the medium term (3 to 12 months post intervention) ‐ follow‐up period, Outcome 14 Change in meta cognition (self‐reported).
Comparison 13 Cognitive training vs control in the medium term (3 to 12 months post intervention) ‐ follow‐up period, Outcome 15 Change in meta cognition (informant‐reported).
Comparison 13 Cognitive training vs control in the medium term (3 to 12 months post intervention) ‐ follow‐up period, Outcome 16 Change in capacity for activities of daily living.
Comparison 13 Cognitive training vs control in the medium term (3 to 12 months post intervention) ‐ follow‐up period, Outcome 17 Change in behavioural and psychological symptoms of dementia (BPSD).
Comparison 13 Cognitive training vs control in the medium term (3 to 12 months post intervention) ‐ follow‐up period, Outcome 18 Change in general health and quality of life.
Comparison 13 Cognitive training vs control in the medium term (3 to 12 months post intervention) ‐ follow‐up period, Outcome 19 Change in participants' mood.
Comparison 13 Cognitive training vs control in the medium term (3 to 12 months post intervention) ‐ follow‐up period, Outcome 23 Change in executive function.
| Cognitive training compared to control immediately post intervention for people with mild to moderate dementia | ||||||
| Patient or population: people with mild to moderate dementia | ||||||
| Outcomes | Anticipated absolute effects* (95% CI) | Relative effect | No. of participants | Certainty of the evidence | Comments | |
| Risk with control immediately post intervention | Risk with cognitive training | |||||
| Change in a global measure of cognition (composite) | Mean change in a global measure of cognition (composite) was 0 | SMD 0.42 higher | ‐ | 1389 | ⊕⊕⊕⊝ | Cognitive training probably has a modest effect on global cognition (based on a composite score) |
| Change in a global measure of cognition | Mean change in a global measure of cognition was 0 | SMD 0.65 higher | ‐ | 1288 | ⊕⊕⊝⊝ | Cognitive training may have a moderate effect on performance in global cognition (based on a screening measure). |
| Change in delayed memory | Mean change in delayed memory was 0 | SMD 0.81 higher | ‐ | 543 | ⊕⊝⊝⊝ | We are unable to determine whether there is any effect on delayed memory due to the very low quality of evidence |
| Change in participants' mood | Mean change in participants' mood was 0 | SMD 0.72 higher | ‐ | 577 | ⊕⊝⊝⊝ | We are unable to determine whether there is any effect on participants' mood due to the very low quality of evidence |
| Change in capacity for activities of daily living | Mean change in capacity for activities of daily living was 0 SD | SMD 0.12 SD higher | ‐ | 687 | ⊕⊕⊝⊝ | Cognitive training may not have an effect on capacity for activities of daily living |
| Participant burden (retention rates) | Study population | OR 0.73 | 1282 | ⊕⊕⊝⊝ | Cognitive training may not be associated with an increase in participant burden as reflected in retention rates | |
| 908 per 1000 | 878 per 1000 | |||||
| Change in mood and well‐being (caregiver) | Mean change in mood and well‐being (caregiver) was 0 | SMD 0.98 higher | ‐ | 36 | ⊕⊕⊕⊝ | Cognitive training probably has a large effect on mood and well‐being in the caregiver |
| *The risk in the intervention group (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI). | ||||||
| GRADE Working Group grades of evidence. | ||||||
| aInconsistency: downgraded 1 point for serious concerns regarding heterogeneity in effect size, which is moderate and statistically significant. Heterogeneity does not seem to be well explained by investigated effect moderators. bInconsistency: downgraded 2 points for very serious concerns regarding heterogeneity in effect size, which is relatively large and statistically significant. Heterogeneity does not seem to be well explained by investigated effect moderators. cPublication bias: downgraded 1 point for strongly suspected publication bias based on visual inspection of the funnel plot, raising the possibility that small negative studies may remain unpublished. dImprecision: downgraded 1 point for serious concerns related to imprecision because the confidence interval crosses the no treatment threshold. eImprecision: downgraded 2 points for very serious concerns related to imprecision because the confidence interval includes positive effect, negligible effect, and effect in the direction of the control group. fRisk of bias: outcome estimation is based on a single study with several limitations related to unclear or high risk of bias in several domains. gImprecision: downgraded 1 point for serious concerns related to imprecision because the analysis is based on fewer than 400 participants; however the confidence interval does not cross the no effect threshold. | ||||||
| Cognitive training compared to control in the medium term (3 to 12 months post intervention) for people with mild to moderate dementia | ||||||
| Patient or population: people with mild to moderate dementia | ||||||
| Outcomes | Anticipated absolute effects* (95% CI) | Relative effect | No. of participants | Certainty of the evidence | Comments | |
| Risk with control in the medium term (3 to 12 months post intervention) | Risk with cognitive training | |||||
| Change in a global measure of cognition (composite) | Mean change in a global measure of cognition (composite) was set at 0 SDs | SMD 0.65 higher | ‐ | 387 | ⊕⊝⊝⊝ | We are unable to determine whether there is any effect on global cognition (composite) due to the very low quality of evidence |
| Change on global cognition (screening) (Global cog) | Mean change in global cognition (screening) was set at 0 SDs | SMD 1.33 higher | ‐ | 387 | ⊕⊝⊝⊝ | We are unable to determine whether there is any effect on performance in global cognition due to the very low quality of evidence |
| Change in disease progression | Mean change in disease progression was set at 0 SDs | SMD 0.55 higher | ‐ | 98 | ⊕⊝⊝⊝ | We are unable to determine whether CT slows down disease progression due to the very low quality of evidence |
| Change in delayed memory | Mean change in delayed memory was set at 0 SDs | SMD 0.97 SD higher | ‐ | 253 | ⊕⊝⊝⊝ | We are unable to determine whether there is any effect on performance in delayed memory due to the very low quality of evidence |
| Change in capacity for activities of daily living | Mean change in capacity for activities of daily living was set at 0 SDs | SMD 0.22 higher | ‐ | 64 | ⊕⊕⊝⊝ | Cognitive training may not have an effect on capacity for activities of daily living |
| Change in participants' mood | Mean change in participants' mood was set at 0 SDs | SMD 0.21 higher | ‐ | 30 | ⊕⊕⊝⊝ | Cognitive training may not have an effect on participants' mood |
| Change in mood and well‐being (caregiver) | ‐ | See comment | ‐ | (0 studies) | ‐ | No studies have evaluated this outcome in the intermediate term |
| *The risk in the intervention group (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI). | ||||||
| GRADE Working Group grades of evidence. | ||||||
| aRisk of bias: downgraded 2 points for very serious concerns related to risk of bias: removal of high‐risk studies leads to reasonably large changes in the effect estimate. bInconsistency: downgraded 1 point for serious concerns regarding heterogeneity in effect size, which is large and statistically significant. However, heterogeneity seems to be partially explained by investigated effect moderators. cImprecision: downgraded 2 points for very serious concerns related to imprecision because the analysis is based on fewer than 400 participants, and the confidence interval crosses the no effect threshold. dInconsistency: downgraded 2 points for very serious concerns regarding heterogeneity in effect size, which is relatively large and statistically significant. Heterogeneity does not seem to be well explained by investigated effect moderators. eImprecision: downgraded 1 point for serious concerns related to imprecision because the analysis is based on fewer than 400 participants; however the confidence interval does not cross the no effect threshold. | ||||||
| Cognitive training compared to alternative treatment immediately post intervention for people with mild to moderate dementia | ||||||
| Patient or population: people with mild to moderate dementia | ||||||
| Outcomes | Anticipated absolute effects* (95% CI) | Relative effect | No. of participants | Certainty of the evidence | Comments | |
| Risk with alternative treatment immediately post intervention | Risk with cognitive training | |||||
| Change in a global measure of cognition (composite) | Mean change in a global measure of cognition (composite) was 0 SD | SMD 0.21 SD higher | ‐ | 769 | ⊕⊕⊝⊝ | Cognitive training may not have an effect on global cognition |
| Change in a global measure of cognition | Mean change in a global measure of cognition was 0 | SMD 0.16 higher | ‐ | 724 | ⊕⊝⊝⊝ | We are unable to determine whether there is any effect on global cognition (as measured by a screening tool) due to very low quality of evidence |
| Change in delayed memory | Mean change in delayed memory was 0 | SMD 0.71 higher | ‐ | 147 | ⊕⊝⊝⊝ | We are unable to determine whether there is any effect on performance in delayed memory due to very low quality of the evidence |
| Change in participants' mood | Mean change in participants' mood was 0 | SMD 0.11 lower | ‐ | 543 | ⊕⊕⊕⊝ | Cognitive training probably has no effect on participants' mood |
| Change in capacity for activities of daily living | Mean change in capacity for activities of daily living was 0 | SMD 0.25 lower | ‐ | 525 | ⊕⊕⊕⊝ | Cognitive training probably has no effect on capacity for activities of daily living |
| Participant burden (retention rates) | Study population | OR 0.78 | 639 | ⊕⊝⊝⊝ | We are unable to determine whether cognitive training increases participant burden (as measured by retention rates) | |
| 773 per 1000 | 727 per 1000 | |||||
| Change in mood and well‐being (caregiver) | Mean change in mood and well‐being (caregiver) was 0 | SMD 1.5 higher | ‐ | 88 | ⊕⊕⊕⊝ | Cognitive training probably has a large effect on mood and well‐being in the caregiver |
| *The risk in the intervention group (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI). | ||||||
| GRADE Working Group grades of evidence. | ||||||
| aImprecision: downgraded 2 points for very serious concerns related to imprecision because the confidence interval includes positive effect, negligible effect, and effect in the direction of the control group. bInconsistency: downgraded 1 point for serious concerns regarding heterogeneity in effect size, which is moderate and statistically significant. Heterogeneity does not seem to be well explained by investigated effect moderators. cInconsistency: downgraded 2 points for very serious concerns regarding heterogeneity in effect size, which is relatively large and statistically significant. Heterogeneity does not seem to be well explained by investigated effect moderators. dImprecision: downgraded 2 points for very serious concerns related to imprecision because the analysis is based on fewer than 400 participants, and the confidence interval crosses the no effect threshold. eImprecision: downgraded 1 point for serious concerns related to imprecision because the sample size includes fewer than 400 participants. | ||||||
| Cognitive training compared to alternative treatment in the medium term (3 to 12 months post intervention) for people with mild to moderate dementia | ||||||
| Patient or population: people with mild to moderate dementia | ||||||
| Outcomes | Anticipated absolute effects* (95% CI) | Relative effect | No. of participants | Certainty of the evidence | Comments | |
| Risk with alternative treatment in the medium term (3 to 12 months post intervention) | Risk with cognitive training | |||||
| Change in a global measure of cognition (composite) | Mean change in a global measure of cognition (composite) was set at 0 SDs | SMD 1.31 SD higher | ‐ | 73 | ⊕⊝⊝⊝ | We are unable to determine whether there is any effect on global cognition (composite) due to very low quality of the evidence |
| Change in a global measure of cognition | Mean change in a global measure of cognition was set at 0 SDs | SMD 3.2 higher | ‐ | 73 | ⊕⊝⊝⊝ | We are unable to determine whether there is any effect on performance in a screening measure of global cognition due to very low quality of the evidence |
| Change in disease progression | ‐ | See comment | ‐ | (0 studies) | ‐ | None of the included studies have evaluated this outcome |
| Change in delayed memory | Mean change in delayed memory was set at 0 SDs | SMD 3.13 higher | ‐ | 73 | ⊕⊝⊝⊝ | We are unable to determine whether there is any effect on performance in delayed memory due to very low quality of the evidence |
| Change in participants' mood | Mean change in participants' mood was set at 0 SDs | SMD 0.66 lower | ‐ | 39 | ⊕⊕⊝⊝ | Cognitive training may not have an effect on a participants' mood |
| Change in capacity for activities of daily living | ‐ | See comment | ‐ | (0 studies) | ‐ | None of the included studies have evaluated this outcome |
| Change in mood and well‐being (caregiver) | ‐ | See comment | ‐ | (0 studies) | ‐ | None of the included studies have evaluated this outcome |
| *The risk in the intervention group (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI). | ||||||
| GRADE Working Group grades of evidence. | ||||||
| aImprecision: downgraded 2 points for very serious concerns related to imprecision because the confidence interval includes positive effect, negligible effect, and effect in the direction of the control group. | ||||||
| Study | Condition | Sample size (at baseline) | Age, mean (SD), range | Gender balance (m:f) | Education | Medications (number or proportion on dementia‐related medication) | Baseline MMSE score | Retention rates | Adverse reactions |
| Cognitive training | 10 | 74 (range 68 to 75) | 5:5 | Attended college = 2 | None | Not reported | 100% | "many subjects complained of tiring" | |
| Control | 10 | 76 (range 70 to 93) | 3:7 | Attended college = 1 | None | Not reported | 100% | Not specified | |
| Cognitive training | Not reported (18 completed the study) | 65.9 (6.28) | 9:9 | Not reported | None | 20.55 (4.42) | Not reported | Not specified | |
| Control (social support) | Not reported (17 completed the study) | 66.63 (10.17) | 10:7 | Not reported | None | 20.23 (4.10) | Not reported | Not specified | |
| Control (CT+pyritinol) | 17 | 67.18 (8.51) | Not reported | 88.88 | Not reported | 21.64 (4.55) | Not reported | Not specified | |
| Control (CT+phosphatidylserine) | 18 | 66.74 (6.93) | Not reported | 125 | Not reported | 20.88 (4.73) | Not reported | Not specified | |
| Cognitive training | 25 | Not reported | Not reported | Not reported | Not reported | 109.8 (12.0) DRS | Not reported | Not specified | |
| Passive control | 25 | Not reported | Not reported | Not reported | Not reported | 109.2 (11.7) DRS | Not reported | Not specified | |
| Active control | 28 | Not reported | not reported | Not reported | Not reported | 110 (12.2) DRS | Not reported | Not specified | |
| Cognitive training | 12 | NA | NA | NA | NA | NA | NA | NA | |
| Cognitive training+AChE‐I | 12 | Not reported | Not reported | Not reported | All | 17.33 (3.39) | 100% | Not specified | |
| Control (placebo drug) | 12 | Not reported | Not reported | Not reported | All | 17.44 (4.67) | 100% | Not specified | |
| Control (AChE‐I) | 12 | Not reported | Not reported | Not reported | All | 17 (3.20) | 100% | Not specified | |
| Cognitive training | 21 | Not reported | Not reported | Not reported | Not reported | Not assessed | Not reported | Not specified | |
| Passive control | 15 | Not reported | Not reported | Not reported | Not reported | Not assessed | Not reported | Not specified | |
| Dyadic counselling control | 29 | Not reported | Not reported | Not reported | Not reported | Not assessed | Not reported | Not specified | |
| Seminar groups control | 22 | Not reported | Not reported | Not reported | Not reported | Not assessed | Not reported | Not specified | |
| Early‐stage daycare control | 16 | Not reported | Not reported | Not reported | Not reported | Not assessed | Not reported | Not specified | |
| Cognitive training | 19 | 68.67 (3.86) | 10:9 | 15.06 (3.86) | 5 | 21.84 (4.03) | 100% | Not specified | |
| Control | 18 | 72.56 (7.62) | 6:12 | 12.97 (2.56) | 4 | 22.78 (4.45) | 100% | Not specified | |
| Cognitive training (group and individual) ‐ shared data | 16 | 72.9 (6.7) | Not reported | 15.0 (4.0) | Not reported | 22.9 (3.6) | 87.5% (missed: 2 participants from group CT) | Not specified | |
| Control | 8 | 73.9 (7.2) | Not reported | 15.0 (4.0) | Not reported | 26.6 (2.5) | 100% | Not specified | |
| Cognitive training | 19 | 77. 8 (6.9) | 9:8 | 12.7 (2.1) | All participants: donepezil | 24.3 (2.2) | 89.4% (missed: 3 participants) | Not specified | |
| Control | 20 | 76.0 (7.7) | 5:12 | 13.1 (3.5) | All participants: donepezil | 25.1 (1.7) | 85% (missed: 3 participants) | Not specified | |
| Cognitive training | 7 | Not reported | Not reported | Not reported | All | 22.9 (3.1) | 100% | Not specified | |
| Control | 5 | Not reported | Not reported | Not reported | All | 23.1 (1.8) | 80% (missed: 1 participant) | Not specified | |
| Cognitive training | 10 | 74.8 (6.7) | 6:4 | Not reported | Not reported | 22.9 (4.15) | 100% | Not specified | |
| Control | 10 | 77.0 (6.6) | 6:4 | Not reported | Not reported | 18.6 (5.7) | 90% (missed: 1 participant) | Not specified | |
| Cognitive training | 16 | 85.1 (5.4) (range 76 to 96) | Not reported | Not reported | Not reported | 19.9 (7.0) | 100% | Not specified | |
| Control | 16 | 86.3 (4.9) (range 78 to 96) | Not reported | Not reported | Not reported | 19.6 (5.4) | Not reported | Not specified | |
| Cognitive training (recollection) | 12 | 81.58 | 4:8 | 10.92 (2.94) | Not reported | 24 (3.05) | Not reported | Not specified | |
| Cognitive training (recognition) | 12 | 82.67 | 4:8 | 12.08 (2.07) | Not reported | 24.83 (2.12) | Not reported | Not specified | |
| Control | 12 | 79.33 (3.85) | 5:7 | 11.08 (3.85) | Not reported | 25.83 (1.40) | Not reported | Not specified | |
| Cognitive training (BBA) | 15 | 75.80 (4.27) | 9:6 | 7.46 (1.84) | All participants on IaCHe | 19.33 (2.48) | Not reported | Not specified | |
| Cognitive training (IPP) | 15 | 75.60 (4.55) | 8:7 | 8.40 (2.77) | All participants on IaCHe | 20 (2.92) | Not reported | Not specified | |
| Control | 15 | 75.86 (4.15) | 8:7 | 7.26 (3.34) | All participants on IaCHe | 20.44 (1.90) | Not reported | Not specified | |
| Cognitive training | 5 | 68.8 (10.0) | 2:3 | 9.0 (1.2) | Not reported | 20.2 (2.8) | Not reported | Not specified | |
| Control | 5 | 70.0 (5.9) | 2:3 | 9.6 (1.9) | Not reported | 20.6 (4.1) | Not reported | Not specified | |
| Cognitive training | 20 | 82.9 (3.6) | 2:18 | 6.7 (2.9) | Not reported | 24.4 (2.8) | 100% | Not specified | |
| Control | 20 | 81.8 (5.5) | 5:15 | 8.25 (3.6) | Not reported | 25 (2.6) | 100% | Not specified | |
| Cognitive training | 16 | 78.19 (5.50) | Not reported | 7.25 (3.24) | All participants: donepezil 5 or 10 mg/d | 20.25 (2.95) | Not reported | Not specified | |
| Control | 16 | 77.72 (5.06) | Not reported | 5.61 (2.30) | All participants: donepezil 5 or 10 mg/d | 21.94 (2.01) | Not reported | Not specified | |
| Cognitive training (CELP) | 6 | Not reported | 1:6 | Nil: 42.8% | Not reported | 15.3 (2.7) | Not reported | Not specified | |
| Cognitive training (TELP) | 6 | Not reported | 3:3 | Nil: 16.7% | Not reported | 17.6 (4.7) | Not reported | Not specified | |
| Control | 7 | Reported | 2:4 | Nil: 33.3% | Not reported | 17 (3.5) | Not reported | Not specified | |
| Cognitive training | 10 | 82.6 (4.85) | Not reported | 4.6 (1.5) | Not reported | 20.1 (4.2) | 100% | Not specified | |
| Control (occupational therapy) | 10 | 84.5 (5.06) | Not reported | 4.3 (1.82) | Not reported | 19.7 (3.8) | 100% | Not specified | |
| Control (no treatment) | 10 | 84.7 (4.42) | Not reported | 4 (1.15) | Not reported | 18.8 (2.68) | 100% | Not specified | |
| Cognitve training (LSS‐tele) | 7 | 86 (5.1) | 2:5 | 6 (3.5) | Not reported | 23.7 (2.8) | Not reported | Not specified | |
| Cognitive training (LSS‐direct) | 10 | 82.7 (6) | 3:7 | 6.7 (3.3) | Not reported | 24.9 (2.5) | Not reported | Not specified | |
| Control | 10 | 82.3 (5.9) | 1:9 | 8.7 (3.7) | Not reported | 24.8 (2.7) | Not reported | Not specified | |
| Cognitive training | 32 | Not reported | Not reported | Not reported | 100% donepezil | Not reported | 84.3% | Not specified | |
| Control muscular relaxation | 34 | Not reported | Not reported | Not reported | 100% donepezil | Not reported | 97% | Not specified | |
| Control mindfulness | 36 | Not reported | Not reported | Not reported | 100% donepezil | Not reported | 97.2% | Not specified | |
| Control | 25 | Not reported | Not reported | Not reported | 100% donepezil | Not reported | 100% | Not specified | |
| Cognitive training | 22 | 70.4 (7.9) | 8:14 | 8.7 (3.8) | Not reported | 23.1 (2.1) | 100% | Not specified | |
| Control | 21 | 71.4 (8.2) | 7:14 | 8.5 (3.1) | Not reported | 22.8 (1.8) | 100% | Not specified | |
| Cognitive training | 170 | 78.5 (7.2) | 69:99 (data from 168 participants) | No diploma: 10% | 89.4% IaCHe, memantine | 21.5 (3.2) | 72.94% (missed: 46 participants) | Not specified | |
| Usual care | 154 | 78.7 (6.5) | 63:90 (data from 154 participants) | No diploma: 15.6% | 86.4% IaCHe, memantine | 21.6 (3.3) | 70.78% (missed: 45 participants) | Not specified | |
| Reminiscence therapy | 172 | 78.8 (6.9) | 61:108 (data from 169 participants) | No diploma: 16.3% | 90.1% IaCHe, memantine | 21.1 (3.1) | 68.60% (missed: 54 participants) | Not specified | |
| Individualised cognitive rehabilitation | 157 | 78.9 (6.2) | 64:92 (data from 172 participants) | No diploma: 17.2% | 86.6% IaCHe, memantine | 21.6 (3.0) | 77.07% (missed: 36 participants) | Not specified | |
| Cognitive training | 40 | 76.5 (2.88) | 13:27 | 8.53 (3) | 36/40 | 22.65 (1.74) | 100% | Not specified | |
| Control | 40 | 76,33 (3,83) | 16:24 | 8.12 (2.79) | 38/40 | 23.05 (2.44) | 100% | Not specified | |
| Cognitive training (spaced retrieval) | 48 | 83.10 (5.0) | 33:13 | Illiterate: 14 (30, 4) | Not reported | 12.33 (5.41) | 95.83% (missed: 2 participants) | Not specified | |
| Cognitive training (spaced retrieval+Montessori activities) | 52 | 82.69 (6.81) | 37:12 | Illiterate: 9 (18, 4) | Not reported | 12.08 (4.05) | 94.23% (missed: 3 participants) | Not specified | |
| Control | 48 | 81.82 (5.89) | Male 29 (64, 4) | Illiterate: 13 (28, 9) | Not reported | 11.84 (5.49) | 93.75% (missed: 3 participants) | Not specified | |
| Cognitive training | 42 | 76.5 (5.7) | 13:29 | 8.8 (3.6) | Not reported | 23.4 (1.9) | 94.79% (from the 3 groups, not only PWD) | Not specified | |
| Control | 39 | 76.9 (5.7) | 11:28 | 9.2 (3.7) | Not reported | 23.4 (1.7) | 89.14% (from the 3 groups, not only PWD) | Not specified | |
| Cognitive training | 51 | 76.5 (4.3) | 40:60 | 5.9 (4.1) | Not reported | 20.2 (3.7) | 94.11% (missed: 3 participants) | Not specified | |
| Control | 50 | 78.7 (5.9) | 28:72 | 4.5 (2.3) | Not reported | 20.3 (3.5) | 94% retention (missed: 3 participants) | Not specified | |
| Cognitive training | 20 | 86 (9) | 5:15 | Not reported | No anti‐dementia drugs reported | 14.0 (1.6) | 100% | Not specified | |
| Aerobic exercise | 20 | 84 (7) | 4:16 | Not reported | No anti‐dementia drugs reported | 13.7 (2.3) | 100% | Not specified | |
| Aerobic exercise+Cognitive training | 20 | 85 (8) | 6:14 | Not reported | No anti‐dementia drugs reported | 13.8 (1.5) | 100% | Not specified | |
| Control | 20 | 84 (10) | 17:13 | Not reported | No anti‐dementia drugs reported | 14.2 (1.5) | 100% | Not specified | |
| Cognitive training | 17 | 73.4 (5.7) | Not reported | 9.9 (4.2) | All were on inhibitors of cholinesterase, used for at least 2 years | 23.2 (1.6) | 100% | Not specified | |
| Alternative treatment (cognitive stimulation) | 21 | 74.2 (5.6) | Not reported | 9.5 (4.1) | All were on inhibitors of cholinesterase, used for at least 2 years | 23.1 (1.4) | 100% | Not specified | |
| Control | 17 | 73.3 (4.9) | Not reported | 9.8 (4.0) | All were on inhibitors of cholinesterase, used for at least 2 years | 22.5 (0.9) | 100% | Not specified | |
| Cognitive training | 8 | (53 to 80) | 4:4 | (10 to 17) | 5 participants on anti‐dementia medication | 24 (3.55) | 100% | Not specified | |
| Control | 10 | (59 to 83) | 5:3 | (11 to 17) | All 8 participants were on anti‐dementia medication | 21.75 (3.24) | 80% (missed: 2 participants) | Not specified | |
| VR group ‐ AD | 10 | 86.60 | 1:9 | 9.80 (3.97) | Not reported | 22.05 (1.62) | 100% | Not specified | |
| VR group ‐ normal ageing | 8 | 86.62 (6.19) | 4:4 | 9.12 (5.05) | Not reported | 27.73 (2.02) | 100% | Not specified | |
| Control | 10 | 88.70 (3.59) | 2:8 | 7.00 (5.00) | Not reported | 20.79 (1.80) | 100% | Not specified | |
| Cognitive training | 13 | 71.69 (7.88) | 3:10 | 6.92 (2.46) | Not reported | 23.62 (1.94) | 100% (4 dropped out before treatment) | No adverse effects | |
| Alternative treatment (music therapy) | 13 | 73.92 (7.74) | 7:6 | 10.46 (5.3) | Not reported | 22.85 (6.28) | 100% (4 dropped out before treatment) | No adverse effects | |
| Alternative treatment (neuroeducation) | 13 | 75.31 (5.56) | 8:5 | 7.31 (4.01) | Not reported | 21.15 (3.48) | 100% (3 dropped out before treatment) | No adverse effects | |
| Cognitive training | 54 | 74.26 (6.97) | 28:26 | 8.64 (4.21) | 78% AChEIs | 22.20 (2.37) | 88.80% (missed: 6 participants) | 2 falls (group is not reported) and 2 deaths (1 from each group). Study authors stated that these events were not related to any of the experimental procedures performed | |
| Control | 86 | 76.01 (6.46) | 34:52 | 8.40 (4.12) | 88% AChEIs, | 22.89 (2.72) | 100% | 2 falls (group is not reported) and 2 deaths (1 from each group). Study authors stated that these events were not related to any of the experimental procedures performed | |
| Cognitive training | 76 | 82.6 (5.5) | 34.2% male | 32 < 8 years | 60 (78.9%) taking AD medications; 33 (43.4%) taking anticholinergics | 21.0 (4.3) | 68 of 76 | Not specified | |
|
| Control | 71 | 83.6 (5.4) | 21.1% male | 36 < 8 years | 62 (87.4%) taking AD medications; 37 (52.1%) taking anticholinergics | 19.9 (3.9) | 49 of 71 | Not specified |
| Date in the table, in some cases, are reported only for those participants who completed the interventions. AChEI: anti‐cholinesterase inhibitor. AD: Alzheimer's disease. BBA: Big Brain Academy. CELP: computerised errorless learning‐based memory training programme. CT: cognitive traininng. IPP: Integrated Psychostimulation Program. LSS: lexical‐semantic simulation. TELP: therapist‐led errorless programme. VR: virtual reality. | |||||||||
| Study | Duration (weeks) | Session frequency (per week) | Total number of sessions | Session duration (minutes) | Total direct intervention (minutes) | Total direct intervention (hours) | Session format | Adherence rates | Fidelity measures |
| 6 (cognitive training) | 3 | 18 | Approx. 35 | Approx. 630 | Approx. 10.5 | Individual, with a research assistant | Not reported | Not reported | |
| NA (control) | NA | NA | NA | NA | NA | NA | NA | NA | |
| 24 (cognitive training) | 2 | 48 | 60 | 2880 | 48 | Individual | Not reported | Not reported | |
| 24 (social support) | 1 | 24 | 60 | 1440 | 24 | Individual | Not reported | Not reported | |
| 24 (cognitive training+pyritinol) | 2 | 48 | 60 | 2880 | 48 | Individual | Not reported | Not reported | |
| 24 (cognitive training+phosphatidylserine) | 2 | 48 | 60 | 2880 | 48 | Individual | Not reported | Not reported | |
| 12 (cognitive training) | 6 | 72 | 60 | 4320 | 72 | Individual | Not reported | Caregiver and care recipient were trained together in programme implementation techniques. Return demonstrations by caregivers were required to validate training | |
| NA (passive control) | NA | NA | NA | NA | NA | NA | NA | NA | |
| 12 (active control) | Not reported | Not reported | Not reported | Not reported | Not reported | Not reported | Not reported | Caregiver and care recipient were trained together in programme implementation techniques. Return demonstrations by caregivers were required to validate training | |
| NA (cognitive training) | NA | NA | NA | NA | NA | NA | NA | NA | |
| 12 (cognitive training+ChE‐I, after 12 weeks on drug) | 2 | 24 | 45 | 1080 | 18 | Individual | Not reported | Not reported | |
| 12 (placebo drug) | NA | NA | NA | NA | NA | NA | Not reported | Not reported | |
| 12 (AChE‐I, after 12 weeks on drug) | NA | NA | NA | NA | NA | NA | Not reported | Not reported | |
| 8 (cognitive training) | 1 | 8 | 90 | 720 | 12 | Individual, with help from caregiver | Not reported | Ongoing monitoring of personnel performance to ensure uniformity and consistency of administration of assessments or interventions | |
| 8 (dyadic counselling) | 1 | 8 | 90 | 720 | 12 | Dyad | Not reported | Ongoing monitoring of personnel performance to ensure uniformity and consistency of administration of assessments or interventions | |
| 8 (seminar groups) | 1 | 8 | 90 | 720 | 12 | Group | Not reported | Ongoing monitoring of personnel performance to ensure uniformity and consistency of administration of assessments or interventions | |
| 8 (daycare) | 7 | 8 | 240 | 1920 | 32 | Group | Not reported | Ongoing monitoring of personnel performance to ensure uniformity and consistency of administration of assessments or interventions | |
| NA (wait‐list control) | NA | NA | NA | NA | NA | NA | NA | NA | |
| 5 (cognitive training) | 1 | 5 | 60 | 300 | 5 | Individual | Not reported | Not reported | |
| 5 (control) | 1 | 5 | 60 | 300 | 5 | Individual | Not reported | Not reported | |
| 5 (cognitive training ‐ group) | 1 | 5 | 60 | 300 | 5 | Group | Not reported | Not reported | |
| 6 (cognitive training ‐ individual) | 1 | 6 | Not reported | Not reported | Not reported | Individual | Not reported | Not reported | |
| NA (wait‐list control) | NA | NA | NA | NA | NA | NA | NA | NA | |
| 6 (cognitive training) | 1 | 6 | Not reported | Not reported | Not reported | Group, with a clinical neuropsychologist | 1 participant did not complete the first session, and 2 participants did not complete the fourth session | "All sessions were identical for all participants, with the memory group instructor relying on a trainer's manual with scripts for how to present the information" | |
| 6 (control) | 1 | 6 | 45 | 270 | 4.5 | Group, with a clinical neuropsychologist | 4 participants missed 1 session, and 1 participant missed 2 sessions | Not reported | |
| 4 (cognitive training) | 3 | 12 | 60 | 720 | 12 | Individual, with a neuropsychologist | Not reported | Not reported | |
| 4 (control) | 3 | 12 | 60 | 720 | 12 | Individual, with a neuropsychologist | Not reported | Not reported | |
| 8 (cognitive training ‐ collaborative intervention) | 1 | 8 | 30 to 40 | Approx. 280 | Approx. 4.5 | Dyads, with a research assistant | Not reported | Not reported | |
| 8 (cognitive training ‐ individual intervention) | 1 | 8 | 30 to 40 | Approx. 280 | Approx. 4.5 | Individual, with a research assistant | Not reported | Not reported | |
| NA (control group) | NA | NA | NA | NA | NA | NA | NA | NA | |
| 24 (cognitive training) | 2 to 6 | 48 to 144 | Approx. 20 | 960 to 2880 | 16 to 48 | Individual, with the possibility to ask staff members for advice | Not reported | Not reported | |
| NA (control) | NA | NA | NA | NA | NA | NA | Not reported | Not reported | |
| 2 (cognitive training ‐ recollection) | 12 | 24 | 60 | 1440 | 24 | Not reported | Not reported | Not reported | |
| 2 (cognitive training ‐ recognition) | 12 | 24 | 60 | 1440 | 24 | Not reported | Not reported | Not reported | |
| NA (control) | NA | NA | NA | NA | NA | NA | NA | NA | |
| 12 (cognitive training ‐ BBA) | 3 | 36 | 60 | 2160 | 36 | Individual, with an OT and a psychologist | Not reported | Not reported | |
| 12 (cognitive training ‐ IPP) | 3 | 36 | 60 | 2160 | 36 | Individual, with an OT and a psychologist | Not reported | Not reported | |
| NA (control) | NA | NA | NA | NA | NA | NA | NA | NA | |
| 12 (cognitive training) | 1 | 12 | 50 | 600 | 10 | Individual, with a neuropsychologist. | Not reported | Not reported | |
| 12 (control) | 1 | 12 | 50 | 600 | 10 | Individual, with a clinical psychologist. | Not reported | Not reported | |
| 12 (cognitive training) | 2 | 24 | 60 | 1440 | 24 | Group, provided by a neuropsychologist | Not reported | Not reported | |
| 12 (control) | 2 | 24 | 60 | 1440 | 24 | Group, provided by a neuropsychologist | Not reported | Not reported | |
| 20 (cognitive training) | 5 | 100 | 120 | 12000 | 200 | Group, supervised by a neuropsychologist | Not reported | Not reported | |
| 20 (control) | Presumed to be 5 | Not reported | Not reported | Not reported | Not reported | Group | Not reported | Not reported | |
| 6 (cognitive training ‐ CELP) | 2 | 12 | 30 | 360 | 6 | Individual, with a therapist | Not reported | Not reported | |
| 6 (cognitive training ‐ TELP) | 2 | 12 | 30 | 360 | 6 | Individual, with a therapist | Not reported | Not reported | |
| 6 (active control) | 2 | 12 | 30 | 360 | 6 | Not reported | Not reported | Not reported | |
| 8 (cognitive training) | 5 | 40 | 60 | 2400 | 40 | With a therapist | Not reported | Not reported | |
| 8 (control ‐ occupational therapy) | 5 | 40 | 60 | 2400 | 40 | Not reported | Not reported | Not reported | |
| NA (control ‐ usual care) | NA | NA | NA | NA | NA | NA | NA | NA | |
| 12 (cognitive training ‐ LSS‐tele) | 2 | 24 | 60 | 1440 | 24 | Small groups, provided by a therapist | Not reported | Not reported | |
| 12 (cognitive training ‐ LSS‐direct) | 2 | 24 | 60 | 1440 | 24 | Small groups, provided by a therapist | Not reported | Not reported | |
| 12 (control) | 2 | 24 | 60 | 1440 | 24 | Small groups, provided by a therapist | Not reported | Not reported | |
| 104 (cognitive training) | 3 (IPP) | 288 | 90 | 25920 | 432 | Group, with a clinical psychologist | Not reported | Not reported | |
| 104 (muscular relaxation) | 3 | 288 | 90 | 25920 | 432 | Group, with a clinical psychologist | Not reported | Not reported | |
| 104 (mindfulness) | 3 | 288 | 90 | 25920 | 432 | Group, with a clinical psychologist | Not reported | Not reported | |
| NA (passive control) | NA | NA | NA | NA | NA | NA | Not reported | Not reported | |
| 8 (cognitive training) | 1 | 8 | 60 | 480 | 8 | Individual and in a group | Not reported | Not reported | |
| 8 (control) | 1 | 8 | 60 | 480 | 8 | Not reported | Not reported | Not reported | |
| 96 (cognitive training) | 1 (during the first 3 months); 1 every 6 weeks (for the next 21 months) | 15 | 90 | 1350 | 22.5 | Groups | Not reported | Manual detailing the guidelines of each intervention was provided. Standardised procedures to guarantee homogeneity. Professional visits to therapists to ensure that interventions were applied in accordance with protocol | |
| NA (control ‐ usual care) | NA | NA | NA | NA | NA | NA | NA | NA | |
| 96 (reminiscence therapy) | 1 (during the first 3 months); 1 every 6 weeks (for the next 21 months) | 15 | 90 | 1350 | 22.5 | Groups | Not reported | Manual detailing the guidelines of each intervention was provided. Standardised procedures to guarantee homogeneity. Professional visits to therapists to ensure that interventions were applied in accordance with protocol | |
| 96 (cognitive rehabilitation) | 1 (during the first 3 months); 1 every 6 weeks (for the next 21 months) | 15 | 90 | 1350 | 22.5 | Individual | Not reported | Manual detailing the guidelines of each intervention was provided. Standardised procedures to guarantee homogeneity. Professional visits to therapists to ensure that interventions were applied in accordance with protocol | |
| 12 (cognitive training) | 3 | 36 | 30 | 1080 | 18 | Individual, with a neuropsychologist | Not reported | Not reported | |
| 12 (control) | 3 | 36 | 30 | 1080 | 18 | Individual, with a neuropsychologist | Not reported | Not reported | |
| 6 (cognitive training ‐ spaced retrieval) | 5 | 30 | 40 | 1200 | 20 | With a trainer | Not reported | Not reported | |
| 6 (cognitive training ‐ spaced retrieval+Montessori activities) | 5 | 30 | 40 | 1200 | 20 | With a trainer | Not reported | Not reported | |
| na (control) | NA | NA | NA | NA | NA | NA | NA | NA | |
| 12 (cognitive training) | 2 | 24 | 60 | 1440 | 24 | Small groups, provided by a cognitive therapist | Not reported | Not reported | |
| 12 (control) | NA | NA | NA | NA | NA | NA | NA | NA | |
| 10 (cognitive training) | 1 | 10 | 45 | 450 | 7.5 | Individually, with homewrok exercises with support of a caregiver | Not reported | Not reported | |
| 10 (control) | 1 | 10 | 45 | 450 | 7.5 | Not reported | Not reported | Not reported | |
| 12 (cognitive training) | 5 | 60 | 60 | 3600 | 60 | Performed in collaboration with patients’ caregivers | 85±12% in the CT group | Not reported | |
| 12 (aerobic exercise) | 5 | 60 | 60 | 3600 | 60 | Performed in collaboration with patients’ caregivers | 78±8% in the AE group | Not reported | |
| 12 (aerobic exercise+cognitive training) | 5 | 60 | 60 | 3600 | 60 | Performed in collaboration with patients’ caregivers | 75±14% in the AE+CT group | Not reported | |
| NA (control) | NA | NA | NA | NA | NA | NA | NA | NA | |
| 16 (cognitive training) | 3 | 48 | 90 | 4320 | 72 | Individual with licensed psychologist | Not reported | Not reported | |
| 16 (cognitive stimulation) | 3 | 48 | 90 | 4320 | 72 | Individual with licensed psychologist | Not reported | Not reported | |
| 16 (control) | NA | NA | NA | NA | NA | NA | Not reported | Not reported | |
| 12 (cognitive training) | 5 | 60 | Approx. 15 | Approx. 900 | Approx. 15 | Individual homework, with 1 meeting per month | 100% | Not reported | |
| 12 (cognitive rehabilitation) | 2 | 24 | 60 | 1440 | 24 | Small group guided by a psychologist and an occupational therapist | 100% (including only the 8 participants who completed the study and were, therefore, analysed) | Intervention was based on the CORDIAL programme, via a manual‐guided approach | |
| 12 (cognitive training) | 2 | 24 | 45 | 1080 | 18 | Small groups of 3 participants, guided by a neuropsychologist | Not reported | CT was co‐ordinated by a neuropsychologist using defined materials and procedures | |
| 12 (music therapy) | 2 | 24 | 45 | 1080 | 18 | Small groups of 3 participants, guided by a music therapist | Not reported | Active music therapy was provided by a music therapist. Sessions were videotaped and evaluated via a structured assessment | |
| 12 (neuroeducation) | 2 | 24 | 45 | 1080 | 18 | Small groups of 3 participants, co‐ordinated by a neurologist | Not reported | Not reported | |
| 3‐4 (VR group ‐ AD) | 3 | 10 | 20 | 200 | 3.3 | Individual with a neuropsychologist | Not reported | Not reported | |
| 3‐4 (VR group ‐ normal ageing) | 3 | 10 | 20 | 200 | 3.3 | Individual with a neuropsychologist | Not reported | Not reported | |
| NA (control) | NA | NA | NA | NA | NA | Underwent traditional cognitive rehabilitative activities with the neuropsychological staff | NA | NA | |
| 24 (cognitive training) | 2 | 48 | 75 | 3600 | 60 | Group | 11% (6 participants) attended less than 80% of sessions of the first period of the study (from T0 to T1). | Study authors reported high adherence to a strict protocol | |
| NA | NA | NA | NA | NA | NA | NA | NA | NA | |
| 12 (cognitive training) | 2 | 24 | 45 | 1080 | 18 | Group/individual when required | Mean attendance at 22 (92%) sessions | CT was administered by trained psychology students under the supervision of an experienced neuropsychologist | |
|
| NA (control) | NA | NA | NA | NA | NA | NA | NA | NA |
| AChEI: anti‐cholinesterase inhibitor. AD: Alzheimer's disease. BBA: Big Brain Academy. CELP: computerised errorless learning‐based memory training programme. ChEI: cholinesterase inhibitor. CT: cognitive traininng. IPP: Integrated Psychostimulation Program. LSS: lexical‐semantic simulation. NA: not applicable. TELP: therapist‐led errorless programme. VR: virtual reality. | |||||||||
| Outcome or subgroup title | No. of studies | No. of participants | Statistical method | Effect size |
| 1 Change in a global measure of cognition (composite) Show forest plot | 26 | 1389 | Std. Mean Difference (Random, 95% CI) | 0.42 [0.23, 0.61] |
| 2 Change in a global measure of cognition (composite)_zero correlation Show forest plot | 26 | 1389 | Std. Mean Difference (Random, 95% CI) | 0.24 [0.12, 0.36] |
| 3 Change in a global measure of cognition Show forest plot | 20 | 1288 | Std. Mean Difference (IV, Random, 95% CI) | 0.65 [0.26, 1.05] |
| 4 Change in a global measure of cognition_zero correlation Show forest plot | 20 | 1287 | Std. Mean Difference (IV, Random, 95% CI) | 0.27 [0.04, 0.50] |
| 5 Change in disease progression Show forest plot | 5 | 215 | Std. Mean Difference (IV, Random, 95% CI) | 1.07 [0.59, 1.55] |
| 6 Change in delayed memory Show forest plot | 11 | 543 | Std. Mean Difference (IV, Random, 95% CI) | 0.81 [0.29, 1.32] |
| 7 Change in immediate memory Show forest plot | 17 | 762 | Std. Mean Difference (IV, Random, 95% CI) | 0.74 [0.37, 1.12] |
| 8 Change in attention and working memory Show forest plot | 12 | 551 | Std. Mean Difference (IV, Random, 95% CI) | 0.56 [0.08, 1.05] |
| 9 Change in language (naming) Show forest plot | 5 | 311 | Std. Mean Difference (IV, Random, 95% CI) | 0.62 [0.11, 1.12] |
| 10 Change in verbal letter fluency Show forest plot | 12 | 544 | Std. Mean Difference (IV, Random, 95% CI) | 0.22 [‐0.07, 0.50] |
| 11 Change in verbal category fluency Show forest plot | 9 | 475 | Std. Mean Difference (IV, Random, 95% CI) | 0.52 [0.23, 0.81] |
| 12 Change in executive function Show forest plot | 11 | 511 | Std. Mean Difference (IV, Random, 95% CI) | 0.75 [0.28, 1.22] |
| 13 Change in speed of information processing Show forest plot | 6 | 201 | Std. Mean Difference (IV, Random, 95% CI) | 0.22 [‐0.11, 0.54] |
| 14 Change in meta cognition (self‐reported) Show forest plot | 2 | 41 | Std. Mean Difference (IV, Random, 95% CI) | 0.50 [‐0.15, 1.14] |
| 15 Change in meta cognition (informant‐reported) Show forest plot | 2 | 56 | Std. Mean Difference (IV, Random, 95% CI) | ‐0.01 [‐1.29, 1.26] |
| 16 Change in participants' mood Show forest plot | 8 | 577 | Std. Mean Difference (IV, Random, 95% CI) | 0.72 [‐0.10, 1.54] |
| 17 Change in capacity for activities of daily living Show forest plot | 10 | 687 | Std. Mean Difference (IV, Random, 95% CI) | 0.12 [‐0.11, 0.35] |
| 18 Change in general health and quality of life Show forest plot | 5 | 630 | Std. Mean Difference (IV, Random, 95% CI) | ‐0.04 [‐0.38, 0.29] |
| 19 Change in behavioural and psychological symptoms of dementia (BPSD) Show forest plot | 6 | 493 | Std. Mean Difference (IV, Random, 95% CI) | 0.44 [‐0.34, 1.22] |
| 20 Participant burden (retention rates) Show forest plot | 17 | 1282 | Odds Ratio (M‐H, Random, 95% CI) | 0.73 [0.37, 1.43] |
| 21 Change in burden of care (CAREGIVER) Show forest plot | 2 | 405 | Std. Mean Difference (IV, Random, 95% CI) | ‐0.11 [‐0.36, 0.15] |
| 22 Change in quality of life (CAREGIVER) Show forest plot | 1 | 36 | Std. Mean Difference (IV, Random, 95% CI) | 0.16 [‐0.50, 0.83] |
| 23 Change in mood and well‐being (CAREGIVER) Show forest plot | 1 | 36 | Std. Mean Difference (IV, Random, 95% CI) | 0.98 [0.27, 1.68] |
| Outcome or subgroup title | No. of studies | No. of participants | Statistical method | Effect size |
| 1 Change in a global measure of cognition (composite) Show forest plot | 7 | 387 | Std. Mean Difference (Random, 95% CI) | 0.65 [0.11, 1.20] |
| 2 Change in a global measure of cognition (composite)_zero correlation Show forest plot | 7 | 387 | Std. Mean Difference (Random, 95% CI) | 0.40 [0.09, 0.71] |
| 3 Change in a global measure of cognition Show forest plot | 6 | 387 | Std. Mean Difference (IV, Random, 95% CI) | 1.33 [0.31, 2.34] |
| 4 Change in a global measure of cognition (zero correlation) Show forest plot | 6 | 387 | Std. Mean Difference (IV, Random, 95% CI) | 0.68 [0.06, 1.30] |
| 5 Change in disease progression Show forest plot | 2 | 98 | Std. Mean Difference (IV, Random, 95% CI) | 0.55 [0.12, 0.98] |
| 6 Change in disease progression (zero correlation) Show forest plot | 2 | 98 | Std. Mean Difference (IV, Random, 95% CI) | 0.28 [‐0.14, 0.71] |
| 7 Change in delayed memory Show forest plot | 4 | 274 | Std. Mean Difference (IV, Random, 95% CI) | 0.97 [0.02, 1.92] |
| 8 Change in immediate memory Show forest plot | 7 | 383 | Std. Mean Difference (IV, Random, 95% CI) | 0.62 [0.00, 1.24] |
| 9 Change in attention and working memory Show forest plot | 3 | 215 | Std. Mean Difference (IV, Random, 95% CI) | 0.50 [‐0.43, 1.43] |
| 10 Change in language (naming) Show forest plot | 4 | 274 | Std. Mean Difference (IV, Random, 95% CI) | 0.71 [0.07, 1.34] |
| 11 Change in verbal letter fluency Show forest plot | 4 | 247 | Std. Mean Difference (IV, Random, 95% CI) | 0.47 [‐0.28, 1.23] |
| 12 Change in verbal category fluency Show forest plot | 3 | 213 | Std. Mean Difference (IV, Random, 95% CI) | 0.78 [0.38, 1.18] |
| 13 Change in executive function Show forest plot | 5 | 330 | Std. Mean Difference (IV, Random, 95% CI) | 0.56 [0.02, 1.10] |
| 14 Change in speed of information processing Show forest plot | 2 | 45 | Std. Mean Difference (IV, Random, 95% CI) | 0.30 [‐0.44, 1.04] |
| 15 Change in meta cognition (self‐reported) Show forest plot | 1 | 19 | Std. Mean Difference (IV, Random, 95% CI) | 0.99 [‐0.01, 1.99] |
| 16 Change in meta cognition (informant‐reported) Show forest plot | 1 | 34 | Std. Mean Difference (IV, Random, 95% CI) | ‐0.06 [‐0.73, 0.62] |
| 17 Change in participants' mood Show forest plot | 2 | 30 | Std. Mean Difference (IV, Random, 95% CI) | 0.21 [‐0.54, 0.96] |
| 18 Change in capacity for activities of daily living Show forest plot | 3 | 64 | Std. Mean Difference (IV, Random, 95% CI) | 0.22 [‐0.50, 0.94] |
| 19 Change in general health and quality of life Show forest plot | 1 | 117 | Std. Mean Difference (IV, Random, 95% CI) | ‐0.02 [‐0.39, 0.35] |
| 20 Change in behavioural and psychological symptoms of dementia (BPSD) Show forest plot | 1 | 11 | Std. Mean Difference (IV, Random, 95% CI) | ‐1.34 [‐2.75, 0.07] |
| 21 Change in burden of care (CAREGIVER) | 0 | 0 | Std. Mean Difference (IV, Random, 95% CI) | 0.0 [0.0, 0.0] |
| 22 Change in quality of life (CAREGIVER) | 0 | 0 | Std. Mean Difference (IV, Random, 95% CI) | 0.0 [0.0, 0.0] |
| 23 Change in mood and well‐being (CAREGIVER) | 0 | 0 | Std. Mean Difference (IV, Random, 95% CI) | 0.0 [0.0, 0.0] |
| Outcome or subgroup title | No. of studies | No. of participants | Statistical method | Effect size |
| 1 Change in a global measure of cognition (composite) Show forest plot | 7 | 769 | Std. Mean Difference (Random, 95% CI) | 0.21 [‐0.23, 0.64] |
| 2 Change in a global measure of cognition (composite)_zero correlation Show forest plot | 7 | 769 | Std. Mean Difference (Random, 95% CI) | ‐0.03 [‐0.23, 0.17] |
| 3 Change in a global measure of cognition Show forest plot | 7 | 724 | Std. Mean Difference (IV, Random, 95% CI) | 0.16 [‐0.28, 0.60] |
| 4 Change in a global measure of cognition_zero correlation Show forest plot | 7 | 724 | Std. Mean Difference (IV, Random, 95% CI) | ‐0.02 [‐0.24, 0.20] |
| 5 Change in disease progression Show forest plot | 3 | 131 | Std. Mean Difference (IV, Random, 95% CI) | 0.15 [‐0.33, 0.63] |
| 6 Change in delayed memory Show forest plot | 3 | 147 | Std. Mean Difference (IV, Random, 95% CI) | 0.71 [‐0.33, 1.75] |
| 7 Change in immediate memory Show forest plot | 3 | 147 | Std. Mean Difference (IV, Random, 95% CI) | 0.51 [‐0.19, 1.21] |
| 8 Change in attention and working memory Show forest plot | 2 | 69 | Std. Mean Difference (IV, Random, 95% CI) | 0.91 [‐0.46, 2.27] |
| 9 Change in language (naming) Show forest plot | 1 | 16 | Std. Mean Difference (IV, Random, 95% CI) | ‐0.63 [‐1.65, 0.38] |
| 10 Change in verbal letter fluency Show forest plot | 3 | 75 | Std. Mean Difference (IV, Random, 95% CI) | 0.34 [‐0.38, 1.05] |
| 11 Change in verbal category fluency Show forest plot | 2 | 55 | Std. Mean Difference (IV, Random, 95% CI) | ‐0.28 [‐1.46, 0.89] |
| 12 Change in executive function Show forest plot | 4 | 163 | Std. Mean Difference (IV, Random, 95% CI) | 1.44 [‐0.26, 3.14] |
| 13 Change in speed of information processing Show forest plot | 2 | 55 | Std. Mean Difference (IV, Random, 95% CI) | 0.00 [‐0.55, 0.55] |
| 14 Change in meta cognition (self‐reported) | 0 | 0 | Std. Mean Difference (IV, Random, 95% CI) | 0.0 [0.0, 0.0] |
| 15 Change in meta cognition (informant‐reported) | 0 | 0 | Std. Mean Difference (IV, Random, 95% CI) | 0.0 [0.0, 0.0] |
| 16 Change in participants' mood Show forest plot | 3 | 543 | Std. Mean Difference (IV, Random, 95% CI) | ‐0.11 [‐0.29, 0.07] |
| 17 Change in capacity for activities of daily living Show forest plot | 3 | 525 | Std. Mean Difference (IV, Random, 95% CI) | ‐0.25 [‐0.43, ‐0.07] |
| 18 Change in general health and quality of life Show forest plot | 4 | 631 | Std. Mean Difference (IV, Random, 95% CI) | ‐0.49 [1.00, 0.02] |
| 19 Change in behavioural and psychological symptoms of dementia (BPSD) Show forest plot | 3 | 672 | Std. Mean Difference (IV, Random, 95% CI) | ‐0.11 [‐0.27, 0.06] |
| 20 Participant burden (retention rates) Show forest plot | 4 | 639 | Odds Ratio (M‐H, Random, 95% CI) | 0.78 [0.24, 2.57] |
| 21 Change in burden of care (CAREGIVER) Show forest plot | 3 | 591 | Std. Mean Difference (IV, Random, 95% CI) | ‐0.15 [‐0.47, 0.17] |
| 22 Change in quality of life (CAREGIVER) Show forest plot | 1 | 88 | Std. Mean Difference (IV, Random, 95% CI) | ‐0.25 [‐0.74, 0.24] |
| 23 Change in mood and well‐being (CAREGIVER) Show forest plot | 1 | 88 | Std. Mean Difference (IV, Random, 95% CI) | 1.50 [0.96, 2.04] |
| Outcome or subgroup title | No. of studies | No. of participants | Statistical method | Effect size |
| 1 Change in a global measure of cognition (composite) Show forest plot | 2 | 73 | Std. Mean Difference (Random, 95% CI) | 1.31 [‐1.03, 3.65] |
| 2 Change in a global measure of cognition (composite)_zero correlation Show forest plot | 2 | 73 | Std. Mean Difference (Random, 95% CI) | 0.62 [‐0.52, 1.75] |
| 3 Change in a global measure of cognition Show forest plot | 2 | 73 | Std. Mean Difference (IV, Random, 95% CI) | 3.20 [‐2.89, 9.29] |
| 4 Change in disease progression (zero correlation) | 0 | 0 | Std. Mean Difference (IV, Random, 95% CI) | 0.0 [0.0, 0.0] |
| 5 Change in disease progression | 0 | 0 | Std. Mean Difference (IV, Random, 95% CI) | 0.0 [0.0, 0.0] |
| 6 Change in delayed memory Show forest plot | 2 | 73 | Std. Mean Difference (IV, Random, 95% CI) | 0.61 [‐1.07, 2.30] |
| 7 Change in immediate memory Show forest plot | 2 | 73 | Std. Mean Difference (IV, Random, 95% CI) | 0.75 [‐0.61, 2.10] |
| 8 Change in attention and working memory Show forest plot | 1 | 39 | Std. Mean Difference (IV, Random, 95% CI) | ‐0.05 [‐0.72, 0.61] |
| 9 Change in language (naming) Show forest plot | 1 | 34 | Std. Mean Difference (IV, Random, 95% CI) | 1.98 [1.14, 2.82] |
| 10 Change in verbal letter fluency Show forest plot | 1 | 39 | Std. Mean Difference (IV, Random, 95% CI) | 0.29 [‐0.38, 0.96] |
| 11 Change in verbal category fluency Show forest plot | 1 | 39 | Std. Mean Difference (IV, Random, 95% CI) | ‐0.08 [‐0.74, 0.59] |
| 12 Change in executive function Show forest plot | 1 | 39 | Std. Mean Difference (IV, Random, 95% CI) | ‐0.30 [‐0.97, 0.37] |
| 13 Change in speed of information processing Show forest plot | 1 | 39 | Std. Mean Difference (IV, Random, 95% CI) | ‐0.11 [‐0.77, 0.56] |
| 14 Change in meta cognition (self‐reported) | 0 | 0 | Std. Mean Difference (IV, Random, 95% CI) | 0.0 [0.0, 0.0] |
| 15 Change in meta cognition (informant‐reported) | 0 | 0 | Std. Mean Difference (IV, Random, 95% CI) | 0.0 [0.0, 0.0] |
| 16 Change in participants' mood Show forest plot | 1 | 39 | Std. Mean Difference (IV, Random, 95% CI) | ‐0.66 [‐1.35, 0.02] |
| 17 Change in capacity for activities of daily living | 0 | 0 | Std. Mean Difference (IV, Random, 95% CI) | 0.0 [0.0, 0.0] |
| 18 Change in general health and quality of life Show forest plot | 1 | 39 | Std. Mean Difference (IV, Random, 95% CI) | 0.33 [‐0.34, 1.00] |
| 19 Change in behavioural and psychological symptoms of dementia (BPSD) | 0 | 0 | Std. Mean Difference (IV, Random, 95% CI) | 0.0 [0.0, 0.0] |
| 20 Change in burden of care (CAREGIVER) | 0 | 0 | Std. Mean Difference (IV, Random, 95% CI) | 0.0 [0.0, 0.0] |
| 21 Change in quality of life (CAREGIVER) | 0 | 0 | Std. Mean Difference (IV, Random, 95% CI) | 0.0 [0.0, 0.0] |
| 22 Change in mood and well‐being (CAREGIVER) | 0 | 0 | Std. Mean Difference (IV, Random, 95% CI) | 0.0 [0.0, 0.0] |
| Outcome or subgroup title | No. of studies | No. of participants | Statistical method | Effect size |
| 1 Change in a global measure of cognition Show forest plot | 20 | 1288 | Std. Mean Difference (IV, Random, 95% CI) | 0.65 [0.26, 1.05] |
| 1.1 Lower risk | 14 | 1010 | Std. Mean Difference (IV, Random, 95% CI) | 0.79 [0.28, 1.30] |
| 1.2 Higher risk | 6 | 278 | Std. Mean Difference (IV, Random, 95% CI) | 0.30 [‐0.26, 0.87] |
| 2 Change in a global measure of cognition_zero correlation Show forest plot | 20 | 1287 | Std. Mean Difference (IV, Random, 95% CI) | 0.27 [0.04, 0.50] |
| 2.1 Lower risk | 14 | 1009 | Std. Mean Difference (IV, Random, 95% CI) | 0.33 [0.03, 0.63] |
| 2.2 Higher risk | 6 | 278 | Std. Mean Difference (IV, Random, 95% CI) | 0.07 [‐0.20, 0.34] |
| 3 Change in a global measure of cognition (composite) Show forest plot | 26 | 1389 | Std. Mean Difference (Random, 95% CI) | 0.42 [0.23, 0.61] |
| 3.1 Lower risk | 19 | 1034 | Std. Mean Difference (Random, 95% CI) | 0.46 [0.19, 0.72] |
| 3.2 Higher risk | 7 | 355 | Std. Mean Difference (Random, 95% CI) | 0.33 [0.12, 0.55] |
| 4 Change in a global measure of cognition (composite)_zero correlation Show forest plot | 26 | 1390 | Std. Mean Difference (Random, 95% CI) | 0.24 [0.12, 0.36] |
| 4.1 Lower risk | 19 | 1035 | Std. Mean Difference (Random, 95% CI) | 0.23 [0.08, 0.38] |
| 4.2 Higher risk | 7 | 355 | Std. Mean Difference (Random, 95% CI) | 0.28 [0.07, 0.49] |
| 5 Change in immediate memory Show forest plot | 17 | 762 | Std. Mean Difference (IV, Random, 95% CI) | 0.74 [0.37, 1.12] |
| 5.1 Lower risk | 13 | 542 | Std. Mean Difference (IV, Random, 95% CI) | 0.95 [0.46, 1.44] |
| 5.2 Higher risk | 5 | 220 | Std. Mean Difference (IV, Random, 95% CI) | 0.33 [0.06, 0.60] |
| 6 Change in delayed memory Show forest plot | 11 | 543 | Std. Mean Difference (IV, Random, 95% CI) | 0.81 [0.29, 1.32] |
| 6.1 Lower risk | 8 | 413 | Std. Mean Difference (IV, Random, 95% CI) | 0.87 [0.16, 1.59] |
| 6.2 Higher risk | 3 | 130 | Std. Mean Difference (IV, Random, 95% CI) | 0.56 [0.21, 0.92] |
| 7 Change in attention and working memory Show forest plot | 12 | 551 | Std. Mean Difference (IV, Random, 95% CI) | 0.56 [0.08, 1.05] |
| 7.1 Lower risk | 9 | 394 | Std. Mean Difference (IV, Random, 95% CI) | 0.57 [‐0.03, 1.17] |
| 7.2 Higher risk | 3 | 157 | Std. Mean Difference (IV, Random, 95% CI) | 0.56 [‐0.57, 1.69] |
| 8 Change in language (naming) Show forest plot | 5 | 311 | Std. Mean Difference (IV, Random, 95% CI) | 0.62 [0.11, 1.12] |
| 9 Change in verbal letter fluency Show forest plot | 12 | 544 | Std. Mean Difference (IV, Random, 95% CI) | 0.22 [‐0.07, 0.50] |
| 10 Change in speed of information processing Show forest plot | 6 | 201 | Std. Mean Difference (IV, Random, 95% CI) | 0.22 [‐0.11, 0.54] |
| 11 Change in executive function Show forest plot | 11 | 511 | Std. Mean Difference (IV, Random, 95% CI) | 0.75 [0.28, 1.22] |
| 12 Change in verbal category fluency Show forest plot | 9 | 475 | Std. Mean Difference (IV, Random, 95% CI) | 0.52 [0.23, 0.81] |
| 12.1 Lower risk | 6 | 318 | Std. Mean Difference (IV, Random, 95% CI) | 0.49 [0.06, 0.93] |
| 12.2 Higher risk | 3 | 157 | Std. Mean Difference (IV, Random, 95% CI) | 0.48 [0.16, 0.80] |
| 13 Change in meta cognition (self‐reported) Show forest plot | 2 | 41 | Std. Mean Difference (IV, Random, 95% CI) | 0.12 [‐0.87, 1.12] |
| 14 Change in meta cognition (informant‐reported) Show forest plot | 2 | 56 | Std. Mean Difference (IV, Random, 95% CI) | ‐0.65 [‐1.19, ‐0.10] |
| 15 Change in participants' mood Show forest plot | 8 | 576 | Std. Mean Difference (IV, Random, 95% CI) | 0.72 [‐0.10, 1.54] |
| 16 Change in capacity for activities of daily living Show forest plot | 10 | 705 | Std. Mean Difference (IV, Random, 95% CI) | 0.12 [‐0.10, 0.34] |
| 16.1 Lower risk | 7 | 516 | Std. Mean Difference (IV, Random, 95% CI) | 0.09 [‐0.19, 0.37] |
| 16.2 Higher risk | 3 | 189 | Std. Mean Difference (IV, Random, 95% CI) | 0.18 [‐0.21, 0.58] |
| 17 Change in general health and quality of life Show forest plot | 4 | 542 | Std. Mean Difference (IV, Random, 95% CI) | ‐0.00 [‐0.42, 0.41] |
| 18 Change in behavioural and psychological symptoms of dementia (BPSD) Show forest plot | 6 | 493 | Std. Mean Difference (IV, Random, 95% CI) | 0.44 [‐0.34, 1.22] |
| 19 Change in disease progression Show forest plot | 5 | 215 | Std. Mean Difference (IV, Random, 95% CI) | 1.07 [0.59, 1.55] |
| 20 Change in burden of care (CAREGIVER) Show forest plot | 2 | 405 | Std. Mean Difference (IV, Random, 95% CI) | ‐0.11 [‐0.36, 0.15] |
| 21 Change in quality of life (CAREGIVER) Show forest plot | 1 | 36 | Std. Mean Difference (IV, Random, 95% CI) | 0.16 [‐0.50, 0.83] |
| 22 Change in mood and well‐being (CAREGIVER) Show forest plot | 1 | 36 | Std. Mean Difference (IV, Random, 95% CI) | 0.98 [0.27, 1.68] |
| 23 Participant burden (retention rates) Show forest plot | 17 | 1282 | Odds Ratio (M‐H, Random, 95% CI) | 0.73 [0.37, 1.43] |
| 24 Change in general health and quality of life Show forest plot | 5 | 630 | Std. Mean Difference (IV, Random, 95% CI) | ‐0.04 [‐0.38, 0.29] |
| Outcome or subgroup title | No. of studies | No. of participants | Statistical method | Effect size |
| 1 Change in a global measure of cognition Show forest plot | 20 | 1288 | Std. Mean Difference (IV, Random, 95% CI) | 0.65 [0.26, 1.05] |
| 1.1 Up to 3 times | 15 | 1112 | Std. Mean Difference (IV, Random, 95% CI) | 0.51 [0.06, 0.95] |
| 1.2 More than 3 times | 5 | 176 | Std. Mean Difference (IV, Random, 95% CI) | 1.14 [0.27, 2.01] |
| 2 Change in a global measure of cognition_zero correlation Show forest plot | 20 | 1287 | Std. Mean Difference (IV, Random, 95% CI) | 0.27 [0.04, 0.50] |
| 2.1 Up to 3 times | 15 | 1111 | Std. Mean Difference (IV, Random, 95% CI) | 0.23 [‐0.01, 0.47] |
| 2.2 More than 3 times | 5 | 176 | Std. Mean Difference (IV, Random, 95% CI) | 0.42 [‐0.30, 1.15] |
| 3 Change in a global measure of cognition (composite) Show forest plot | 26 | 1389 | Std. Mean Difference (Random, 95% CI) | 0.42 [0.23, 0.61] |
| 3.1 Up to 3 times | 20 | 1138 | Std. Mean Difference (Random, 95% CI) | 0.33 [0.13, 0.53] |
| 3.2 More than 3 times | 6 | 251 | Std. Mean Difference (Random, 95% CI) | 0.71 [0.27, 1.14] |
| 4 Change in a global measure of cognition (composite)_zero correlation Show forest plot | 26 | 1338 | Std. Mean Difference (Random, 95% CI) | 0.24 [0.12, 0.36] |
| 4.1 Up to 3 times | 20 | 1139 | Std. Mean Difference (Random, 95% CI) | 0.14 [0.02, 0.26] |
| 4.2 More than 3 times | 6 | 199 | Std. Mean Difference (Random, 95% CI) | 0.54 [0.28, 0.80] |
| 5 Change in immediate memory Show forest plot | 17 | 762 | Std. Mean Difference (IV, Random, 95% CI) | 0.74 [0.37, 1.12] |
| 5.1 Up to 3 times | 14 | 636 | Std. Mean Difference (IV, Random, 95% CI) | 0.73 [0.27, 1.19] |
| 5.2 More than 3 times | 4 | 126 | Std. Mean Difference (IV, Random, 95% CI) | 0.74 [0.29, 1.19] |
| 6 Change in delayed memory Show forest plot | 11 | 543 | Std. Mean Difference (IV, Random, 95% CI) | 0.81 [0.29, 1.32] |
| 7 Change in attention and working memory Show forest plot | 12 | 551 | Std. Mean Difference (IV, Random, 95% CI) | 0.56 [0.08, 1.05] |
| 8 Change in language (naming) Show forest plot | 5 | 311 | Std. Mean Difference (IV, Random, 95% CI) | 0.62 [0.11, 1.12] |
| 9 Change in verbal letter fluency Show forest plot | 12 | 544 | Std. Mean Difference (IV, Random, 95% CI) | 0.22 [‐0.07, 0.50] |
| 9.1 Up to 3 times | 9 | 460 | Std. Mean Difference (IV, Random, 95% CI) | 0.05 [‐0.13, 0.24] |
| 9.2 More than 3 times | 3 | 84 | Std. Mean Difference (IV, Random, 95% CI) | 1.00 [0.09, 1.92] |
| 10 Change in speed of information processing Show forest plot | 6 | 201 | Std. Mean Difference (IV, Random, 95% CI) | 0.22 [‐0.11, 0.54] |
| 11 Change in executive function Show forest plot | 11 | 511 | Std. Mean Difference (IV, Random, 95% CI) | 0.75 [0.28, 1.22] |
| 11.1 Up to 3 times | 8 | 380 | Std. Mean Difference (IV, Random, 95% CI) | 0.57 [0.01, 1.13] |
| 11.2 More than 3 times | 3 | 131 | Std. Mean Difference (IV, Random, 95% CI) | 1.20 [0.20, 2.20] |
| 12 Change in verbal category fluency Show forest plot | 9 | 475 | Std. Mean Difference (IV, Random, 95% CI) | 0.52 [0.23, 0.81] |
| 13 Change in meta cognition (self‐reported) Show forest plot | 2 | 41 | Std. Mean Difference (IV, Random, 95% CI) | 0.12 [‐0.87, 1.12] |
| 14 Change in meta cognition (informant‐reported) Show forest plot | 2 | 56 | Std. Mean Difference (IV, Random, 95% CI) | ‐0.65 [‐1.19, ‐0.10] |
| 15 Change in participants' mood Show forest plot | 8 | 576 | Std. Mean Difference (IV, Random, 95% CI) | 0.72 [‐0.10, 1.54] |
| 16 Change in capacity for activities of daily living Show forest plot | 10 | 705 | Std. Mean Difference (IV, Random, 95% CI) | 0.12 [‐0.10, 0.34] |
| 17 Change in disease progression Show forest plot | 5 | 215 | Std. Mean Difference (IV, Random, 95% CI) | 1.07 [0.59, 1.55] |
| 18 Change in behavioural and psychological symptoms of dementia (BPSD) Show forest plot | 6 | 493 | Std. Mean Difference (IV, Random, 95% CI) | 0.44 [‐0.34, 1.22] |
| 19 Change in attention and working memory Show forest plot | 12 | 551 | Std. Mean Difference (IV, Random, 95% CI) | 0.56 [0.08, 1.05] |
| 20 Change in burden of care (CAREGIVER) Show forest plot | 2 | 405 | Std. Mean Difference (IV, Random, 95% CI) | ‐0.11 [‐0.36, 0.15] |
| 21 Change in quality of life (CAREGIVER) Show forest plot | 1 | 36 | Std. Mean Difference (IV, Random, 95% CI) | 0.16 [‐0.50, 0.83] |
| 22 Change in mood and well‐being (CAREGIVER) Show forest plot | 1 | 36 | Std. Mean Difference (IV, Random, 95% CI) | 0.98 [0.27, 1.68] |
| 23 Participant burden (retention rates) Show forest plot | 17 | 1282 | Odds Ratio (M‐H, Random, 95% CI) | 0.73 [0.37, 1.43] |
| 23.1 Up to 3 times | 14 | 1047 | Odds Ratio (M‐H, Random, 95% CI) | 0.98 [0.53, 1.81] |
| 23.2 More than 3 times | 3 | 235 | Odds Ratio (M‐H, Random, 95% CI) | 0.33 [0.10, 1.09] |
| 24 Change in general health and quality of life Show forest plot | 5 | 630 | Std. Mean Difference (IV, Random, 95% CI) | ‐0.04 [‐0.38, 0.29] |
| Outcome or subgroup title | No. of studies | No. of participants | Statistical method | Effect size |
| 1 Change in a global measure of cognition Show forest plot | 20 | 1288 | Std. Mean Difference (IV, Random, 95% CI) | 0.65 [0.26, 1.05] |
| 1.1 Up to 3 months | 14 | 682 | Std. Mean Difference (IV, Random, 95% CI) | 0.49 [0.09, 0.89] |
| 1.2 More than 3 months | 6 | 606 | Std. Mean Difference (IV, Random, 95% CI) | 1.03 [0.04, 2.02] |
| 2 Change in a global measure of cognition_zero correlation Show forest plot | 20 | 1287 | Std. Mean Difference (IV, Random, 95% CI) | 0.27 [0.04, 0.50] |
| 2.1 Up to 3 months | 14 | 682 | Std. Mean Difference (IV, Random, 95% CI) | 0.15 [‐0.08, 0.38] |
| 2.2 More than 3 months | 6 | 605 | Std. Mean Difference (IV, Random, 95% CI) | 0.51 [‐0.04, 1.05] |
| 3 Change in a global measure of cognition (composite) Show forest plot | 26 | 1389 | Std. Mean Difference (Random, 95% CI) | 0.42 [0.23, 0.61] |
| 3.1 Up to 3 months | 20 | 790 | Std. Mean Difference (Random, 95% CI) | 0.38 [0.18, 0.58] |
| 3.2 More than 3 months | 6 | 599 | Std. Mean Difference (Random, 95% CI) | 0.54 [0.07, 1.01] |
| 4 Change in a global measure of cognition (composite)_zero correlation Show forest plot | 26 | 1390 | Std. Mean Difference (Random, 95% CI) | 0.24 [0.12, 0.36] |
| 4.1 Up to 3 months | 20 | 790 | Std. Mean Difference (Random, 95% CI) | 0.28 [0.14, 0.42] |
| 4.2 More than 3 months | 6 | 600 | Std. Mean Difference (Random, 95% CI) | 0.21 [‐0.03, 0.46] |
| 5 Change in immediate memory Show forest plot | 17 | 762 | Std. Mean Difference (IV, Random, 95% CI) | 0.74 [0.37, 1.12] |
| 5.1 Up to 3 months | 14 | 565 | Std. Mean Difference (IV, Random, 95% CI) | 0.75 [0.29, 1.21] |
| 5.2 More than 3 months | 3 | 197 | Std. Mean Difference (IV, Random, 95% CI) | 0.76 [0.26, 1.26] |
| 6 Change in delayed memory Show forest plot | 11 | 543 | Std. Mean Difference (IV, Random, 95% CI) | 0.81 [0.29, 1.32] |
| 7 Change in attention and working memory Show forest plot | 12 | 551 | Std. Mean Difference (IV, Random, 95% CI) | 0.56 [0.08, 1.05] |
| 8 Change in language (naming) Show forest plot | 5 | 311 | Std. Mean Difference (IV, Random, 95% CI) | 0.62 [0.11, 1.12] |
| 9 Change in verbal letter fluency Show forest plot | 12 | 544 | Std. Mean Difference (IV, Random, 95% CI) | 0.22 [‐0.07, 0.50] |
| 9.1 Up to 3 months | 9 | 350 | Std. Mean Difference (IV, Random, 95% CI) | 0.03 [‐0.23, 0.28] |
| 9.2 More than 3 months | 3 | 194 | Std. Mean Difference (IV, Random, 95% CI) | 0.66 [‐0.05, 1.38] |
| 10 Change in speed of information processing Show forest plot | 6 | 201 | Std. Mean Difference (IV, Random, 95% CI) | 0.22 [‐0.11, 0.54] |
| 11 Change in executive function Show forest plot | 11 | 511 | Std. Mean Difference (IV, Random, 95% CI) | 0.75 [0.28, 1.22] |
| 12 Change in verbal category fluency Show forest plot | 9 | 475 | Std. Mean Difference (IV, Random, 95% CI) | 0.52 [0.23, 0.81] |
| 13 Change in meta cognition (self‐reported) Show forest plot | 2 | 41 | Std. Mean Difference (IV, Random, 95% CI) | 0.12 [‐0.87, 1.12] |
| 14 Change in meta cognition (informant‐reported) Show forest plot | 2 | 56 | Std. Mean Difference (IV, Random, 95% CI) | ‐0.65 [‐1.19, ‐0.10] |
| 15 Change in participants' mood Show forest plot | 8 | 576 | Std. Mean Difference (IV, Random, 95% CI) | 0.72 [‐0.10, 1.54] |
| 16 Change in capacity for activities of daily living Show forest plot | 10 | 705 | Std. Mean Difference (IV, Random, 95% CI) | 0.12 [‐0.10, 0.34] |
| 17 Change in disease progression Show forest plot | 5 | 215 | Std. Mean Difference (IV, Random, 95% CI) | 1.07 [0.59, 1.55] |
| 18 Change in behavioural and psychological symptoms of dementia (BPSD) Show forest plot | 6 | 493 | Std. Mean Difference (IV, Random, 95% CI) | 0.44 [‐0.34, 1.22] |
| 18.1 Up to 3 months | 3 | 92 | Std. Mean Difference (IV, Random, 95% CI) | 0.66 [‐1.70, 3.02] |
| 18.2 More than 3 months | 3 | 401 | Std. Mean Difference (IV, Random, 95% CI) | 0.12 [‐0.29, 0.53] |
| 19 Participant burden (retention rates) Show forest plot | 17 | 1282 | Odds Ratio (M‐H, Random, 95% CI) | 0.73 [0.37, 1.43] |
| 19.1 Up to 3 months | 14 | 761 | Odds Ratio (M‐H, Random, 95% CI) | 0.78 [0.35, 1.73] |
| 19.2 More than 3 months | 3 | 521 | Odds Ratio (M‐H, Random, 95% CI) | 0.24 [0.02, 2.57] |
| 20 Change in burden of care (CAREGIVER) Show forest plot | 2 | 405 | Std. Mean Difference (IV, Random, 95% CI) | ‐0.11 [‐0.36, 0.15] |
| 21 Change in quality of life (CAREGIVER) Show forest plot | 1 | 36 | Std. Mean Difference (IV, Random, 95% CI) | 0.16 [‐0.50, 0.83] |
| 22 Change in mood and well‐being (CAREGIVER) Show forest plot | 1 | 36 | Std. Mean Difference (IV, Random, 95% CI) | 0.98 [0.27, 1.68] |
| 23 Change in general health and quality of life Show forest plot | 5 | 630 | Std. Mean Difference (IV, Random, 95% CI) | ‐0.04 [‐0.38, 0.29] |
| Outcome or subgroup title | No. of studies | No. of participants | Statistical method | Effect size |
| 1 Change in a global measure of cognition Show forest plot | 20 | 1288 | Std. Mean Difference (IV, Random, 95% CI) | 0.65 [0.26, 1.05] |
| 1.1 Traditional | 13 | 975 | Std. Mean Difference (IV, Random, 95% CI) | 0.84 [0.30, 1.39] |
| 1.2 Augmented | 7 | 313 | Std. Mean Difference (IV, Random, 95% CI) | 0.25 [‐0.21, 0.70] |
| 2 Change in a global measure of cognition_zero correlation Show forest plot | 20 | 1287 | Std. Mean Difference (IV, Random, 95% CI) | 0.27 [0.04, 0.50] |
| 2.1 Traditional | 13 | 974 | Std. Mean Difference (IV, Random, 95% CI) | 0.41 [0.11, 0.71] |
| 2.2 Augmented | 7 | 313 | Std. Mean Difference (IV, Random, 95% CI) | ‐0.03 [‐0.33, 0.26] |
| 3 Change in a global measure of cognition (composite) Show forest plot | 26 | 1389 | Std. Mean Difference (Random, 95% CI) | 0.42 [0.23, 0.61] |
| 3.1 Traditional | 17 | 1026 | Std. Mean Difference (Random, 95% CI) | 0.43 [0.18, 0.68] |
| 3.2 Augmented | 9 | 363 | Std. Mean Difference (Random, 95% CI) | 0.37 [0.10, 0.65] |
| 4 Change in a global measure of cognition (composite)_zero correlation Show forest plot | 26 | 1390 | Std. Mean Difference (Random, 95% CI) | 0.24 [0.12, 0.36] |
| 4.1 Traditional | 17 | 1027 | Std. Mean Difference (Random, 95% CI) | 0.30 [0.12, 0.47] |
| 4.2 Augmented | 9 | 363 | Std. Mean Difference (Random, 95% CI) | 0.18 [‐0.02, 0.39] |
| 5 Change in immediate memory Show forest plot | 17 | 762 | Std. Mean Difference (IV, Random, 95% CI) | 0.74 [0.37, 1.12] |
| 5.1 Traditional | 12 | 559 | Std. Mean Difference (IV, Random, 95% CI) | 0.82 [0.33, 1.30] |
| 5.2 Augmented | 5 | 203 | Std. Mean Difference (IV, Random, 95% CI) | 0.53 [0.04, 1.02] |
| 6 Change in delayed memory Show forest plot | 11 | 543 | Std. Mean Difference (IV, Random, 95% CI) | 0.81 [0.29, 1.32] |
| 6.1 Traditional | 7 | 383 | Std. Mean Difference (IV, Random, 95% CI) | 0.86 [0.15, 1.58] |
| 6.2 Augmented | 4 | 160 | Std. Mean Difference (IV, Random, 95% CI) | 0.68 [‐0.11, 1.46] |
| 7 Change in attention and working memory Show forest plot | 12 | 551 | Std. Mean Difference (IV, Random, 95% CI) | 0.56 [0.08, 1.05] |
| 7.1 Traditional | 8 | 379 | Std. Mean Difference (IV, Random, 95% CI) | 0.56 [‐0.17, 1.30] |
| 7.2 Augmented | 4 | 172 | Std. Mean Difference (IV, Random, 95% CI) | 0.51 [0.07, 0.95] |
| 8 Change in language (naming) Show forest plot | 5 | 311 | Std. Mean Difference (IV, Random, 95% CI) | 0.62 [0.11, 1.12] |
| 9 Change in verbal letter fluency Show forest plot | 12 | 544 | Std. Mean Difference (IV, Random, 95% CI) | 0.22 [‐0.07, 0.50] |
| 9.1 Traditional | 8 | 386 | Std. Mean Difference (IV, Random, 95% CI) | 0.26 [‐0.09, 0.62] |
| 9.2 Augmented | 4 | 158 | Std. Mean Difference (IV, Random, 95% CI) | 0.14 [‐0.42, 0.70] |
| 10 Change in speed of information processing Show forest plot | 6 | 201 | Std. Mean Difference (IV, Random, 95% CI) | 0.22 [‐0.11, 0.54] |
| 11 Change in executive function Show forest plot | 11 | 511 | Std. Mean Difference (IV, Random, 95% CI) | 0.75 [0.28, 1.22] |
| 11.1 Traditional | 8 | 442 | Std. Mean Difference (IV, Random, 95% CI) | 0.64 [0.14, 1.14] |
| 11.2 Augmented | 3 | 69 | Std. Mean Difference (IV, Random, 95% CI) | 1.32 [‐0.26, 2.91] |
| 12 Change in verbal category fluency Show forest plot | 9 | 475 | Std. Mean Difference (IV, Random, 95% CI) | 0.52 [0.23, 0.81] |
| 12.1 Traditional | 6 | 323 | Std. Mean Difference (IV, Random, 95% CI) | 0.64 [0.26, 1.01] |
| 12.2 Augmented | 3 | 152 | Std. Mean Difference (IV, Random, 95% CI) | 0.33 [0.00, 0.65] |
| 13 Change in meta cognition (self‐reported) Show forest plot | 2 | 41 | Std. Mean Difference (IV, Random, 95% CI) | 0.12 [‐0.87, 1.12] |
| 14 Change in meta cognition (informant‐reported) Show forest plot | 2 | 56 | Std. Mean Difference (IV, Random, 95% CI) | ‐0.65 [‐1.19, ‐0.10] |
| 15 Change in participants' mood Show forest plot | 8 | 576 | Std. Mean Difference (IV, Random, 95% CI) | 0.72 [‐0.10, 1.54] |
| 15.1 Traditional | 5 | 423 | Std. Mean Difference (IV, Random, 95% CI) | 0.90 [‐0.30, 2.10] |
| 15.2 Augmented | 3 | 153 | Std. Mean Difference (IV, Random, 95% CI) | 0.46 [‐0.94, 1.86] |
| 16 Change in capacity for activities of daily living Show forest plot | 10 | 705 | Std. Mean Difference (IV, Random, 95% CI) | 0.12 [‐0.10, 0.34] |
| 17 Change in disease progression Show forest plot | 5 | 215 | Std. Mean Difference (IV, Random, 95% CI) | 1.07 [0.59, 1.55] |
| 18 Change in behavioural and psychological symptoms of dementia (BPSD) Show forest plot | 6 | 493 | Std. Mean Difference (IV, Random, 95% CI) | 0.44 [‐0.34, 1.22] |
| 19 Participant burden (retention rates) Show forest plot | 17 | 1282 | Odds Ratio (M‐H, Random, 95% CI) | 0.73 [0.37, 1.43] |
| 19.1 Traditional | 10 | 1017 | Odds Ratio (M‐H, Random, 95% CI) | 0.59 [0.23, 1.53] |
| 19.2 Augmented | 7 | 265 | Odds Ratio (M‐H, Random, 95% CI) | 1.02 [0.27, 3.87] |
| 20 Change in burden of care (CAREGIVER) Show forest plot | 2 | 405 | Std. Mean Difference (IV, Random, 95% CI) | ‐0.11 [‐0.36, 0.15] |
| 21 Change in quality of life (CAREGIVER) Show forest plot | 1 | 36 | Std. Mean Difference (IV, Random, 95% CI) | 0.16 [‐0.50, 0.83] |
| 22 Change in mood and well‐being (CAREGIVER) Show forest plot | 1 | 36 | Std. Mean Difference (IV, Random, 95% CI) | 0.98 [0.27, 1.68] |
| 23 Change in general health and quality of life Show forest plot | 5 | 630 | Std. Mean Difference (IV, Random, 95% CI) | ‐0.04 [‐0.38, 0.29] |
| Outcome or subgroup title | No. of studies | No. of participants | Statistical method | Effect size |
| 1 Change in a global measure of cognition Show forest plot | 20 | 1288 | Std. Mean Difference (IV, Random, 95% CI) | 0.65 [0.26, 1.05] |
| 1.1 Multidomain | 16 | 1165 | Std. Mean Difference (IV, Random, 95% CI) | 0.63 [0.19, 1.07] |
| 1.2 Single domain | 4 | 123 | Std. Mean Difference (IV, Random, 95% CI) | 0.75 [‐0.14, 1.63] |
| 2 Change in a global measure of cognition_zero correlation Show forest plot | 20 | 1287 | Std. Mean Difference (IV, Random, 95% CI) | 0.27 [0.04, 0.50] |
| 2.1 Multidomain | 16 | 1164 | Std. Mean Difference (IV, Random, 95% CI) | 0.25 [‐0.01, 0.52] |
| 2.2 Single domain | 4 | 123 | Std. Mean Difference (IV, Random, 95% CI) | 0.37 [‐0.04, 0.79] |
| 3 Change in a global measure of cognition (composite) Show forest plot | 26 | 1389 | Std. Mean Difference (Random, 95% CI) | 0.42 [0.23, 0.61] |
| 3.1 Multidomain | 16 | 990 | Std. Mean Difference (Random, 95% CI) | 0.44 [0.18, 0.71] |
| 3.2 Single domain | 10 | 399 | Std. Mean Difference (Random, 95% CI) | 0.35 [0.10, 0.59] |
| 4 Change in a global measure of cognition (composite)_zero correlation Show forest plot | 26 | 1390 | Std. Mean Difference (Random, 95% CI) | 0.24 [0.12, 0.36] |
| 4.1 Multidomain | 16 | 991 | Std. Mean Difference (Random, 95% CI) | 0.27 [0.10, 0.44] |
| 4.2 Single domain | 10 | 399 | Std. Mean Difference (Random, 95% CI) | 0.23 [0.04, 0.43] |
| 5 Change in immediate memory Show forest plot | 17 | 762 | Std. Mean Difference (IV, Random, 95% CI) | 0.74 [0.37, 1.12] |
| 5.1 Multidomain | 10 | 540 | Std. Mean Difference (IV, Random, 95% CI) | 0.80 [0.24, 1.35] |
| 5.2 Single domain | 7 | 222 | Std. Mean Difference (IV, Random, 95% CI) | 0.58 [0.22, 0.94] |
| 6 Change in delayed memory Show forest plot | 11 | 543 | Std. Mean Difference (IV, Random, 95% CI) | 0.81 [0.29, 1.32] |
| 6.1 Multidomain | 6 | 369 | Std. Mean Difference (IV, Random, 95% CI) | 1.15 [0.32, 1.97] |
| 6.2 Single domain | 5 | 174 | Std. Mean Difference (IV, Random, 95% CI) | 0.41 [‐0.11, 0.94] |
| 7 Change in attention and working memory Show forest plot | 12 | 551 | Std. Mean Difference (IV, Random, 95% CI) | 0.56 [0.08, 1.05] |
| 7.1 Multidomain | 8 | 411 | Std. Mean Difference (IV, Random, 95% CI) | 0.50 [‐0.14, 1.15] |
| 7.2 Single domain | 4 | 140 | Std. Mean Difference (IV, Random, 95% CI) | 0.68 [‐0.14, 1.49] |
| 8 Change in language (naming) Show forest plot | 5 | 311 | Std. Mean Difference (IV, Random, 95% CI) | 0.62 [0.11, 1.12] |
| 9 Change in verbal letter fluency Show forest plot | 12 | 544 | Std. Mean Difference (IV, Random, 95% CI) | 0.22 [‐0.07, 0.50] |
| 9.1 Multidomain | 8 | 406 | Std. Mean Difference (IV, Random, 95% CI) | 0.37 [‐0.04, 0.78] |
| 9.2 Single domain | 4 | 138 | Std. Mean Difference (IV, Random, 95% CI) | ‐0.04 [‐0.37, 0.30] |
| 10 Change in speed of information processing Show forest plot | 6 | 201 | Std. Mean Difference (IV, Random, 95% CI) | 0.22 [‐0.11, 0.54] |
| 11 Change in executive function Show forest plot | 11 | 511 | Std. Mean Difference (IV, Random, 95% CI) | 0.75 [0.28, 1.22] |
| 11.1 Multidomain | 8 | 408 | Std. Mean Difference (IV, Random, 95% CI) | 0.99 [0.44, 1.55] |
| 11.2 Single domain | 3 | 103 | Std. Mean Difference (IV, Random, 95% CI) | 0.08 [‐0.53, 0.68] |
| 12 Change in verbal category fluency Show forest plot | 9 | 475 | Std. Mean Difference (IV, Random, 95% CI) | 0.52 [0.23, 0.81] |
| 12.1 Multidomain | 6 | 371 | Std. Mean Difference (IV, Random, 95% CI) | 0.70 [0.38, 1.02] |
| 12.2 Single domain | 3 | 104 | Std. Mean Difference (IV, Random, 95% CI) | 0.14 [‐0.25, 0.52] |
| 13 Change in meta cognition (self‐reported) Show forest plot | 2 | 41 | Std. Mean Difference (IV, Random, 95% CI) | 0.12 [‐0.87, 1.12] |
| 14 Change in meta cognition (informant‐reported) Show forest plot | 2 | 56 | Std. Mean Difference (IV, Random, 95% CI) | ‐0.65 [‐1.19, ‐0.10] |
| 15 Change in participants' mood Show forest plot | 8 | 576 | Std. Mean Difference (IV, Random, 95% CI) | 0.72 [‐0.10, 1.54] |
| 16 Change in capacity for activities of daily living Show forest plot | 10 | 705 | Std. Mean Difference (IV, Random, 95% CI) | 0.12 [‐0.10, 0.34] |
| 17 Change in disease progression Show forest plot | 5 | 215 | Std. Mean Difference (IV, Random, 95% CI) | 1.07 [0.59, 1.55] |
| 18 Change in behavioural and psychological symptoms of dementia (BPSD) Show forest plot | 6 | 493 | Std. Mean Difference (IV, Random, 95% CI) | 0.44 [‐0.34, 1.22] |
| 19 Participant burden (retention rates) Show forest plot | 17 | 1282 | Odds Ratio (M‐H, Random, 95% CI) | 0.73 [0.37, 1.43] |
| 19.1 Multidomain | 12 | 988 | Odds Ratio (M‐H, Random, 95% CI) | 0.61 [0.21, 1.81] |
| 19.2 Single domain | 5 | 294 | Odds Ratio (M‐H, Random, 95% CI) | 0.66 [0.24, 1.77] |
| 20 Change in burden of care (CAREGIVER) Show forest plot | 2 | 405 | Std. Mean Difference (IV, Random, 95% CI) | ‐0.11 [‐0.36, 0.15] |
| 21 Change in quality of life (CAREGIVER) Show forest plot | 1 | 36 | Std. Mean Difference (IV, Random, 95% CI) | 0.16 [‐0.50, 0.83] |
| 22 Change in mood and well‐being (CAREGIVER) Show forest plot | 1 | 36 | Std. Mean Difference (IV, Random, 95% CI) | 0.98 [0.27, 1.68] |
| 23 Change in general health and quality of life Show forest plot | 5 | 630 | Std. Mean Difference (IV, Random, 95% CI) | ‐0.04 [‐0.38, 0.29] |
| Outcome or subgroup title | No. of studies | No. of participants | Statistical method | Effect size |
| 1 Change in a global measure of cognition Show forest plot | 20 | 1288 | Std. Mean Difference (IV, Random, 95% CI) | 0.65 [0.26, 1.05] |
| 1.1 Passive | 11 | 912 | Std. Mean Difference (IV, Random, 95% CI) | 0.75 [0.22, 1.28] |
| 1.2 Active | 9 | 376 | Std. Mean Difference (IV, Random, 95% CI) | 0.54 [‐0.11, 1.19] |
| 2 Change in a global measure of cognition_zero correlation Show forest plot | 20 | 1287 | Std. Mean Difference (IV, Random, 95% CI) | 0.27 [0.04, 0.50] |
| 2.1 Passive | 11 | 911 | Std. Mean Difference (IV, Random, 95% CI) | 0.27 [‐0.04, 0.58] |
| 2.2 Active | 9 | 376 | Std. Mean Difference (IV, Random, 95% CI) | 0.27 [‐0.10, 0.65] |
| 3 Change in a global measure of cognition (composite) Show forest plot | 26 | 1389 | Std. Mean Difference (Random, 95% CI) | 0.42 [0.23, 0.61] |
| 3.1 Passive | 14 | 875 | Std. Mean Difference (Random, 95% CI) | 0.31 [0.06, 0.55] |
| 3.2 Active | 13 | 514 | Std. Mean Difference (Random, 95% CI) | 0.53 [0.26, 0.81] |
| 4 Change in a global measure of cognition (composite)_zero correlation Show forest plot | 26 | 1390 | Std. Mean Difference (Random, 95% CI) | 0.24 [0.12, 0.36] |
| 4.1 Passive | 14 | 876 | Std. Mean Difference (Random, 95% CI) | 0.24 [0.04, 0.43] |
| 4.2 Active | 13 | 514 | Std. Mean Difference (Random, 95% CI) | 0.30 [0.13, 0.48] |
| 5 Change in immediate memory Show forest plot | 17 | 762 | Std. Mean Difference (IV, Random, 95% CI) | 0.74 [0.37, 1.12] |
| 5.1 Passive | 7 | 311 | Std. Mean Difference (IV, Random, 95% CI) | 0.64 [0.20, 1.08] |
| 5.2 Active | 11 | 451 | Std. Mean Difference (IV, Random, 95% CI) | 0.82 [0.25, 1.39] |
| 6 Change in delayed memory Show forest plot | 11 | 543 | Std. Mean Difference (IV, Random, 95% CI) | 0.81 [0.29, 1.32] |
| 6.1 Passive | 6 | 325 | Std. Mean Difference (IV, Random, 95% CI) | 0.52 [0.11, 0.94] |
| 6.2 Active | 5 | 218 | Std. Mean Difference (IV, Random, 95% CI) | 1.04 [‐0.04, 2.12] |
| 7 Change in attention and working memory Show forest plot | 12 | 551 | Std. Mean Difference (IV, Random, 95% CI) | 0.56 [0.08, 1.05] |
| 7.1 Passive | 4 | 206 | Std. Mean Difference (IV, Random, 95% CI) | 0.37 [‐0.25, 0.99] |
| 7.2 Active | 8 | 345 | Std. Mean Difference (IV, Random, 95% CI) | 0.63 [‐0.03, 1.29] |
| 8 Change in language (naming) Show forest plot | 5 | 311 | Std. Mean Difference (IV, Random, 95% CI) | 0.62 [0.11, 1.12] |
| 9 Change in verbal letter fluency Show forest plot | 12 | 544 | Std. Mean Difference (IV, Random, 95% CI) | 0.22 [‐0.07, 0.50] |
| 9.1 Passive | 4 | 263 | Std. Mean Difference (IV, Random, 95% CI) | 0.35 [‐0.03, 0.72] |
| 9.2 Active | 8 | 281 | Std. Mean Difference (IV, Random, 95% CI) | 0.14 [‐0.27, 0.55] |
| 10 Change in speed of information processing Show forest plot | 6 | 201 | Std. Mean Difference (IV, Random, 95% CI) | 0.22 [‐0.11, 0.54] |
| 11 Change in executive function Show forest plot | 11 | 511 | Std. Mean Difference (IV, Random, 95% CI) | 0.75 [0.28, 1.22] |
| 11.1 Passive | 6 | 285 | Std. Mean Difference (IV, Random, 95% CI) | 1.37 [0.60, 2.14] |
| 11.2 Active | 6 | 226 | Std. Mean Difference (IV, Random, 95% CI) | 0.21 [‐0.11, 0.53] |
| 12 Change in verbal category fluency Show forest plot | 9 | 475 | Std. Mean Difference (IV, Random, 95% CI) | 0.52 [0.23, 0.81] |
| 13 Change in meta cognition (self‐reported) Show forest plot | 2 | 41 | Std. Mean Difference (IV, Random, 95% CI) | 0.12 [‐0.87, 1.12] |
| 14 Change in meta cognition (informant‐reported) Show forest plot | 2 | 56 | Std. Mean Difference (IV, Random, 95% CI) | ‐0.65 [‐1.19, ‐0.10] |
| 15 Change in participants' mood Show forest plot | 8 | 576 | Std. Mean Difference (IV, Random, 95% CI) | 0.72 [‐0.10, 1.54] |
| 15.1 Passive | 3 | 383 | Std. Mean Difference (IV, Random, 95% CI) | 1.02 [‐1.07, 3.10] |
| 15.2 Active | 5 | 193 | Std. Mean Difference (IV, Random, 95% CI) | 0.58 [‐0.34, 1.49] |
| 16 Change in capacity for activities of daily living Show forest plot | 10 | 705 | Std. Mean Difference (IV, Random, 95% CI) | 0.12 [‐0.10, 0.34] |
| 17 Change in disease progression Show forest plot | 5 | 215 | Std. Mean Difference (IV, Random, 95% CI) | 1.07 [0.59, 1.55] |
| 18 Change in behavioural and psychological symptoms of dementia (BPSD) Show forest plot | 6 | 493 | Std. Mean Difference (IV, Random, 95% CI) | 0.44 [‐0.34, 1.22] |
| 19 Participant burden (retention rates) Show forest plot | 17 | 1282 | Odds Ratio (M‐H, Random, 95% CI) | 0.73 [0.37, 1.43] |
| 19.1 Passive | 9 | 910 | Odds Ratio (M‐H, Random, 95% CI) | 0.49 [0.17, 1.40] |
| 19.2 Active | 8 | 372 | Odds Ratio (M‐H, Random, 95% CI) | 1.17 [0.38, 3.64] |
| 20 Change in burden of care (CAREGIVER) Show forest plot | 2 | 405 | Std. Mean Difference (IV, Random, 95% CI) | ‐0.11 [‐0.36, 0.15] |
| 21 Change in quality of life (CAREGIVER) Show forest plot | 1 | 36 | Std. Mean Difference (IV, Random, 95% CI) | 0.16 [‐0.50, 0.83] |
| 22 Change in mood and well‐being (CAREGIVER) Show forest plot | 1 | 36 | Std. Mean Difference (IV, Random, 95% CI) | 0.98 [0.27, 1.68] |
| 23 Change in general health and quality of life Show forest plot | 5 | 630 | Std. Mean Difference (IV, Random, 95% CI) | ‐0.04 [‐0.38, 0.29] |
| Outcome or subgroup title | No. of studies | No. of participants | Statistical method | Effect size |
| 1 Change in a global measure of cognition Show forest plot | 7 | 724 | Std. Mean Difference (IV, Random, 95% CI) | 0.16 [‐0.28, 0.60] |
| 1.1 Up to 3 times | 3 | 551 | Std. Mean Difference (IV, Random, 95% CI) | 0.32 [‐0.48, 1.12] |
| 1.2 More than 3 times | 4 | 173 | Std. Mean Difference (IV, Random, 95% CI) | 0.13 [‐0.63, 0.89] |
| 2 Change in a global measure of cognition_zero correlation Show forest plot | 7 | 724 | Std. Mean Difference (IV, Random, 95% CI) | ‐0.02 [‐0.24, 0.20] |
| 2.1 Up to 3 times | 3 | 551 | Std. Mean Difference (IV, Random, 95% CI) | 0.02 [‐0.35, 0.40] |
| 2.2 More than 3 times | 4 | 173 | Std. Mean Difference (IV, Random, 95% CI) | 0.01 [‐0.41, 0.43] |
| 3 Change in a global measure of cognition (composite) Show forest plot | 7 | 769 | Std. Mean Difference (Random, 95% CI) | 0.21 [‐0.23, 0.64] |
| 3.1 Up to 3 times | 4 | 636 | Std. Mean Difference (Random, 95% CI) | 0.23 [‐0.27, 0.74] |
| 3.2 More than 3 times | 3 | 133 | Std. Mean Difference (Random, 95% CI) | 0.32 [‐0.90, 1.55] |
| 4 Change in a global measure of cognition (composite)_zero correlation Show forest plot | 7 | 769 | Std. Mean Difference (Random, 95% CI) | ‐0.03 [‐0.23, 0.17] |
| 4.1 Up to 3 times | 4 | 636 | Std. Mean Difference (Random, 95% CI) | ‐0.04 [‐0.22, 0.14] |
| 4.2 More than 3 times | 3 | 133 | Std. Mean Difference (Random, 95% CI) | 0.05 [‐0.59, 0.70] |
| 5 Change in immediate memory Show forest plot | 3 | 147 | Std. Mean Difference (IV, Random, 95% CI) | 0.51 [‐0.19, 1.21] |
| 6 Change in delayed memory Show forest plot | 3 | 147 | Std. Mean Difference (IV, Random, 95% CI) | 0.71 [‐0.33, 1.75] |
| 7 Change in attention and working memory Show forest plot | 2 | 69 | Std. Mean Difference (IV, Random, 95% CI) | 0.91 [‐0.46, 2.27] |
| 8 Change in language (naming) Show forest plot | 1 | 16 | Std. Mean Difference (IV, Random, 95% CI) | ‐0.63 [‐1.65, 0.38] |
| 9 Change in verbal letter fluency Show forest plot | 3 | 75 | Std. Mean Difference (IV, Random, 95% CI) | 0.34 [‐0.38, 1.05] |
| 10 Change in verbal category fluency Show forest plot | 2 | 55 | Std. Mean Difference (IV, Random, 95% CI) | ‐0.28 [‐1.46, 0.89] |
| 11 Change in executive function Show forest plot | 4 | 163 | Std. Mean Difference (IV, Random, 95% CI) | 1.44 [‐0.26, 3.14] |
| 12 Change in meta cognition (self‐reported) | 0 | 0 | Std. Mean Difference (IV, Random, 95% CI) | 0.0 [0.0, 0.0] |
| 13 Change in meta cognition (informant‐reported) | 0 | 0 | Std. Mean Difference (IV, Random, 95% CI) | 0.0 [0.0, 0.0] |
| 14 Change in participants' mood Show forest plot | 3 | 543 | Std. Mean Difference (IV, Random, 95% CI) | ‐0.11 [‐0.29, 0.07] |
| 15 Change in capacity for activities of daily living Show forest plot | 3 | 525 | Std. Mean Difference (IV, Random, 95% CI) | ‐0.25 [‐0.43, ‐0.07] |
| 16 Change in behavioural and psychological symptoms of dementia (BPSD) Show forest plot | 3 | 672 | Std. Mean Difference (IV, Random, 95% CI) | ‐0.11 [‐0.27, 0.06] |
| 17 Change in disease progression Show forest plot | 3 | 131 | Std. Mean Difference (IV, Random, 95% CI) | 0.15 [‐0.33, 0.63] |
| 18 Participant burden (retention rates) Show forest plot | 4 | 639 | Odds Ratio (M‐H, Random, 95% CI) | 0.78 [0.24, 2.57] |
| 19 Change in mood and well‐being (CAREGIVER) Show forest plot | 1 | 88 | Std. Mean Difference (IV, Random, 95% CI) | 1.50 [0.96, 2.04] |
| 20 Change in burden of care (CAREGIVER) Show forest plot | 3 | 591 | Std. Mean Difference (IV, Random, 95% CI) | ‐0.15 [‐0.47, 0.17] |
| 21 Change in quality of life (CAREGIVER) Show forest plot | 1 | 88 | Std. Mean Difference (IV, Random, 95% CI) | ‐0.25 [‐0.74, 0.24] |
| 22 Change in speed of information processing Show forest plot | 2 | 55 | Std. Mean Difference (IV, Random, 95% CI) | ‐0.21 [‐0.77, 0.34] |
| 23 Change in general health and quality of life Show forest plot | 4 | 631 | Std. Mean Difference (IV, Random, 95% CI) | ‐0.49 [1.00, 0.02] |
| Outcome or subgroup title | No. of studies | No. of participants | Statistical method | Effect size |
| 1 Change in a global measure of cognition Show forest plot | 7 | 724 | Std. Mean Difference (IV, Random, 95% CI) | 0.16 [‐0.28, 0.60] |
| 1.1 Traditional | 4 | 646 | Std. Mean Difference (IV, Random, 95% CI) | ‐0.19 [‐0.35, ‐0.02] |
| 1.2 Augmented | 3 | 78 | Std. Mean Difference (IV, Random, 95% CI) | 1.04 [‐0.29, 2.36] |
| 2 Change in a global measure of cognition_zero correlation Show forest plot | 7 | 724 | Std. Mean Difference (IV, Random, 95% CI) | ‐0.02 [‐0.24, 0.20] |
| 2.1 Traditional | 4 | 646 | Std. Mean Difference (IV, Random, 95% CI) | ‐0.12 [‐0.29, 0.04] |
| 2.2 Augmented | 3 | 78 | Std. Mean Difference (IV, Random, 95% CI) | 0.44 [‐0.18, 1.06] |
| 3 Change in a global measure of cognition (composite) Show forest plot | 7 | 769 | Std. Mean Difference (Random, 95% CI) | 0.21 [‐0.23, 0.64] |
| 3.1 Traditional | 4 | 643 | Std. Mean Difference (Random, 95% CI) | ‐0.17 [‐0.34, ‐0.00] |
| 3.2 Augmented | 3 | 126 | Std. Mean Difference (Random, 95% CI) | 1.09 [0.14, 2.04] |
| 4 Change in a global measure of cognition (composite)_zero correlation Show forest plot | 7 | 769 | Std. Mean Difference (Random, 95% CI) | ‐0.03 [‐0.23, 0.17] |
| 4.1 Traditional | 4 | 643 | Std. Mean Difference (Random, 95% CI) | ‐0.11 [‐0.28, 0.06] |
| 4.2 Augmented | 3 | 126 | Std. Mean Difference (Random, 95% CI) | 0.43 [‐0.04, 0.90] |
| 5 Change in immediate memory Show forest plot | 3 | 147 | Std. Mean Difference (IV, Random, 95% CI) | 0.51 [‐0.19, 1.21] |
| 6 Change in delayed memory Show forest plot | 3 | 147 | Std. Mean Difference (IV, Random, 95% CI) | 0.71 [‐0.33, 1.75] |
| 7 Change in attention and working memory Show forest plot | 2 | 69 | Std. Mean Difference (IV, Random, 95% CI) | 0.91 [‐0.46, 2.27] |
| 8 Change in language (naming) Show forest plot | 1 | 16 | Std. Mean Difference (IV, Random, 95% CI) | ‐0.63 [‐1.65, 0.38] |
| 9 Change in verbal letter fluency Show forest plot | 3 | 75 | Std. Mean Difference (IV, Random, 95% CI) | 0.34 [‐0.38, 1.05] |
| 10 Change in verbal category fluency Show forest plot | 2 | 55 | Std. Mean Difference (IV, Random, 95% CI) | ‐0.28 [‐1.46, 0.89] |
| 11 Change in executive function Show forest plot | 4 | 163 | Std. Mean Difference (IV, Random, 95% CI) | 1.44 [‐0.26, 3.14] |
| 12 Change in meta cognition (self‐reported) | 0 | 0 | Std. Mean Difference (IV, Random, 95% CI) | 0.0 [0.0, 0.0] |
| 13 Change in meta cognition (informant‐reported) | 0 | 0 | Std. Mean Difference (IV, Random, 95% CI) | 0.0 [0.0, 0.0] |
| 14 Change in participants' mood Show forest plot | 3 | 543 | Std. Mean Difference (IV, Random, 95% CI) | ‐0.11 [‐0.29, 0.07] |
| 15 Change in capacity for activities of daily living Show forest plot | 3 | 525 | Std. Mean Difference (IV, Random, 95% CI) | ‐0.25 [‐0.43, ‐0.07] |
| 16 Change in behavioural and psychological symptoms of dementia (BPSD) Show forest plot | 3 | 672 | Std. Mean Difference (IV, Random, 95% CI) | ‐0.11 [‐0.27, 0.06] |
| 17 Change in disease progression Show forest plot | 3 | 131 | Std. Mean Difference (IV, Random, 95% CI) | 0.15 [‐0.33, 0.63] |
| 18 Participant burden (retention rates) Show forest plot | 4 | 639 | Odds Ratio (M‐H, Random, 95% CI) | 0.78 [0.24, 2.57] |
| 19 Change in mood and well‐being (CAREGIVER) Show forest plot | 1 | 88 | Std. Mean Difference (IV, Random, 95% CI) | 1.50 [0.96, 2.04] |
| 20 Change in burden of care (CAREGIVER) Show forest plot | 3 | 591 | Std. Mean Difference (IV, Random, 95% CI) | ‐0.15 [‐0.47, 0.17] |
| 21 Change in quality of life (CAREGIVER) Show forest plot | 1 | 88 | Std. Mean Difference (IV, Random, 95% CI) | ‐0.25 [‐0.74, 0.24] |
| 22 Change in speed of information processing Show forest plot | 2 | 55 | Std. Mean Difference (IV, Random, 95% CI) | ‐0.21 [‐0.77, 0.34] |
| 23 Change in general health and quality of life Show forest plot | 4 | 631 | Std. Mean Difference (IV, Random, 95% CI) | ‐0.49 [1.00, 0.02] |
| Outcome or subgroup title | No. of studies | No. of participants | Statistical method | Effect size |
| 1 Change in a global measure of cognition Show forest plot | 6 | 387 | Std. Mean Difference (IV, Random, 95% CI) | 1.33 [0.31, 2.34] |
| 2 Change in a global measure of cognition (zero correlation) Show forest plot | 6 | 387 | Std. Mean Difference (IV, Random, 95% CI) | 0.68 [0.06, 1.30] |
| 3 Change in a global measure of cognition (composite) Show forest plot | 7 | Std. Mean Difference (Random, 95% CI) | 0.65 [0.11, 1.20] | |
| 3.1 Up to 3 months | 3 | Std. Mean Difference (Random, 95% CI) | ‐0.05 [‐0.54, 0.43] | |
| 3.2 More than 3 months | 4 | Std. Mean Difference (Random, 95% CI) | 1.03 [0.33, 1.72] | |
| 4 Change in a global measure of cognition (composite)_zero correlation Show forest plot | 7 | Std. Mean Difference (Random, 95% CI) | 0.40 [0.09, 0.71] | |
| 4.1 Up to 3 months | 3 | Std. Mean Difference (Random, 95% CI) | ‐0.06 [‐0.54, 0.42] | |
| 4.2 More than 4 months | 4 | Std. Mean Difference (Random, 95% CI) | 0.57 [0.21, 0.93] | |
| 5 Change in disease progression (zero correlation) Show forest plot | 2 | 98 | Std. Mean Difference (IV, Random, 95% CI) | 0.28 [‐0.14, 0.71] |
| 6 Change in disease progression Show forest plot | 2 | 98 | Std. Mean Difference (IV, Random, 95% CI) | 0.55 [0.12, 0.98] |
| 7 Change in immediate memory Show forest plot | 7 | 383 | Std. Mean Difference (IV, Random, 95% CI) | 0.62 [0.00, 1.24] |
| 7.1 Up to 3 months | 3 | 64 | Std. Mean Difference (IV, Random, 95% CI) | ‐0.34 [‐1.12, 0.43] |
| 7.2 More than 3 months | 4 | 319 | Std. Mean Difference (IV, Random, 95% CI) | 1.14 [0.53, 1.74] |
| 8 Change in delayed memory Show forest plot | 4 | 270 | Std. Mean Difference (IV, Random, 95% CI) | 0.97 [0.02, 1.92] |
| 9 Change in language (naming) Show forest plot | 4 | 274 | Std. Mean Difference (IV, Random, 95% CI) | ‐0.87 [‐3.81, 2.08] |
| 10 Change in verbal letter fluency Show forest plot | 4 | 247 | Std. Mean Difference (IV, Random, 95% CI) | 0.47 [‐0.28, 1.23] |
| 11 Change in verbal category fluency Show forest plot | 3 | 213 | Std. Mean Difference (IV, Random, 95% CI) | 0.78 [0.38, 1.18] |
| 12 Change in attention and working memory Show forest plot | 3 | 215 | Std. Mean Difference (IV, Random, 95% CI) | 0.50 [‐0.43, 1.43] |
| 13 Change in speed of information processing Show forest plot | 2 | 45 | Std. Mean Difference (IV, Random, 95% CI) | 0.30 [‐0.44, 1.04] |
| 14 Change in meta cognition (self‐reported) Show forest plot | 1 | 19 | Std. Mean Difference (IV, Random, 95% CI) | 0.99 [‐0.01, 1.99] |
| 15 Change in meta cognition (informant‐reported) Show forest plot | 1 | 34 | Std. Mean Difference (IV, Random, 95% CI) | ‐0.06 [‐0.73, 0.62] |
| 16 Change in capacity for activities of daily living Show forest plot | 3 | 64 | Std. Mean Difference (IV, Random, 95% CI) | 0.22 [‐0.50, 0.94] |
| 17 Change in behavioural and psychological symptoms of dementia (BPSD) Show forest plot | 1 | 11 | Std. Mean Difference (IV, Random, 95% CI) | ‐1.34 [‐2.75, 0.07] |
| 18 Change in general health and quality of life Show forest plot | 1 | 117 | Std. Mean Difference (IV, Random, 95% CI) | ‐0.02 [‐0.39, 0.35] |
| 19 Change in participants' mood Show forest plot | 2 | 30 | Std. Mean Difference (IV, Random, 95% CI) | 0.21 [‐0.54, 0.96] |
| 20 Change in mood and well‐being (CAREGIVER) | 0 | 0 | Std. Mean Difference (IV, Random, 95% CI) | 0.0 [0.0, 0.0] |
| 21 Change in burden of care (CAREGIVER) | 0 | 0 | Std. Mean Difference (IV, Random, 95% CI) | 0.0 [0.0, 0.0] |
| 22 Change in quality of life (CAREGIVER) | 0 | 0 | Std. Mean Difference (IV, Random, 95% CI) | 0.0 [0.0, 0.0] |
| 23 Change in executive function Show forest plot | 5 | 330 | Std. Mean Difference (IV, Random, 95% CI) | 0.56 [0.02, 1.10] |
