Vitamin E for Alzheimer's dementia and mild cognitive impairment
Información
- DOI:
- https://doi.org/10.1002/14651858.CD002854.pub4Copiar DOI
- Base de datos:
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- Cochrane Database of Systematic Reviews
- Versión publicada:
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- 27 enero 2017see what's new
- Tipo:
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- Intervention
- Etapa:
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- Review
- Grupo Editorial Cochrane:
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Grupo Cochrane de Demencia y trastornos cognitivos
- Copyright:
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- Copyright © 2017 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
Cifras del artículo
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Autores
Contributions of authors
Original: NT drew up the protocol. M Isaac (MI) planned the review and protocol, selected studies, critiqued the trials, advised on analyses, revised drafts of protocol and review and supervised the review process.
Update 2006: MI and Rebecca Quinn (RQ) reviewed and selected the included studies. MI extracted the data, performed the analysis and wrote the draft. NT contributed to the text and supervised. The search was carried out by Dymphna Hermans.
Update 2012: NF and MI reviewed and selected the included studies. NF extracted the data and wrote the draft. Annalie R Clark (AC), Jennifer Rusted (JR) and NT contributed to the text. JR and NT supervised. The search was carried out by Anna‐Noel Storr.
Update 2016: NF and DL independently reviewed and extracted descriptive data from included studies. NF, NT and DL independently extracted outcome data. NF wrote the initial draft. DL, MI and NF all contributed to the text. NT made the final decision on any disagreements between authors. The search was carried out by Anna‐Noel Storr.
Sources of support
Internal sources
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Centre for Dementia Studies, Brighton & Sussex Medical School, UK.
External sources
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NIHR, UK.
This update was supported by the National Institute for Health Research (NIHR), via Cochrane Infrastructure funding to the Cochrane Dementia and Cognitive Improvement group. The views and opinions expressed therein are those of the authors and do not necessarily reflect those of the Systematic Reviews Programme, NIHR, National Health Service or the Department of Health
Declarations of interest
Nicolas Farina ‐ None known
David Llewellyn ‐ None known
Mokhtar Gad El Kareem Nasr Isaac‐ None known
Naji Tabet ‐ None known
Acknowledgements
The review authors are grateful to Sue Marcus, Managing Editor, Cochrane Dementia and Cognitive Improvement Group, for her support throughout the review.
The review authors would also like to thank Dr Jenny McCleery, Assistant Co‐ordinating Editor, Cochrane Dementia and Cognitive Improvement Group, for her comments and contributions in the amendment process of the review (June 2012 and April 2016).
Version history
| Published | Title | Stage | Authors | Version |
| 2017 Apr 18 | Vitamin E for Alzheimer's dementia and mild cognitive impairment | Review | Nicolas Farina, David Llewellyn, Mokhtar Gad El Kareem Nasr Isaac, Naji Tabet | |
| 2017 Jan 27 | Vitamin E for Alzheimer's dementia and mild cognitive impairment | Review | Nicolas Farina, David Llewellyn, Mokhtar Gad El Kareem Nasr Isaac, Naji Tabet | |
| 2012 Nov 14 | Vitamin E for Alzheimer's dementia and mild cognitive impairment | Review | Nicolas Farina, Mokhtar Gad El Kareem Nasr Isaac, Annalie R Clark, Jennifer Rusted, Naji Tabet | |
| 2008 Jul 16 | Vitamin E for Alzheimer's disease and mild cognitive impairment | Review | Mokhtar Gad El Kareem Nasr Isaac, Rebecca Quinn, Naji Tabet | |
| 2000 Oct 23 | Vitamin E for Alzheimer's disease and mild cognitive impairment | Review | Mokhtar Gad El Kareem Nasr Isaac, Rebecca Quinn, Naji Tabet | |
Differences between protocol and review
We included 'Summary of findings' tables and GRADE evaluation.
The methods of the review were updated to comply with the most recent version of the Cochrane Handbook for Systematic Reviews of Interventions (Version 5.1; Higgins 2011).
Since the June 2012 update, one new author DL has been added. AC and JR have been removed as authors.
Keywords
MeSH
Medical Subject Headings (MeSH) Keywords
- Activities of Daily Living;
- alpha-Tocopherol [adverse effects, *therapeutic use];
- Alzheimer Disease [*drug therapy, mortality];
- Antioxidants [adverse effects, *therapeutic use];
- Cognition [drug effects];
- Cognitive Dysfunction [*drug therapy, mortality];
- Disease Progression;
- Outcome Assessment, Health Care;
- Randomized Controlled Trials as Topic;
- Vitamin E [adverse effects, *therapeutic use];
Medical Subject Headings Check Words
Humans;
PICO
Study flow diagram for study for the search April 2016.
Risk of bias summary: review authors' judgements about each risk of bias item for each included study.
Risk of bias graph: review authors' judgements about each risk of bias item presented as percentages across all included studies.
Comparison 1 Vitamin E (capsules 2000 IU/day in two divided doses) versus placebo in people with Alzheimer's disease, Outcome 1 Alzheimer's Disease Assessment Scale ‐ Cognitive subscale (ADAS‐Cog) (least square (LS) mean change from baseline at 6 to 48 months): completers.
Comparison 1 Vitamin E (capsules 2000 IU/day in two divided doses) versus placebo in people with Alzheimer's disease, Outcome 2 Alzheimer's Disease Cooperative Study/Activities of Daily Living (ADCS‐ADL) (LS mean change from baseline at 6 to 48 months): completers.
Comparison 1 Vitamin E (capsules 2000 IU/day in two divided doses) versus placebo in people with Alzheimer's disease, Outcome 3 Deaths (number of deaths over 48 months).
Comparison 1 Vitamin E (capsules 2000 IU/day in two divided doses) versus placebo in people with Alzheimer's disease, Outcome 4 Serious adverse events (number of participants reporting ≥ 1 serious adverse event over 48 months).
Comparison 1 Vitamin E (capsules 2000 IU/day in two divided doses) versus placebo in people with Alzheimer's disease, Outcome 5 Neuropsychiatric Inventory (NPI) (LS mean change from baseline at 6 to 48 months): completers.
Comparison 1 Vitamin E (capsules 2000 IU/day in two divided doses) versus placebo in people with Alzheimer's disease, Outcome 6 Mini‐Mental State Examination (MMSE) (LS mean change from baseline at 6 to 48 months): completers.
Comparison 1 Vitamin E (capsules 2000 IU/day in two divided doses) versus placebo in people with Alzheimer's disease, Outcome 7 Adverse events (number of participants reporting ≥ 1 adverse event over 48 months).
Comparison 2 Vitamin E (capsules 2000 IU/day in two divided doses) versus placebo in people with mild cognitive impairment, Outcome 1 Progression to Alzheimer's disease (AD) (number of people progressing to AD by 36 months).
Comparison 2 Vitamin E (capsules 2000 IU/day in two divided doses) versus placebo in people with mild cognitive impairment, Outcome 2 Deaths (number of deaths over 36 months).
| Vitamin E (capsules 2000 IU/day in 2 divided doses) compared to placebo for people with Alzheimer's disease | ||||||
| Patient or population: people with Alzheimer's disease Settings: multicentre, US Intervention: vitamin E (capsules 2000 IU/day in 2 divided doses) Comparison: placebo | ||||||
| Outcomes | Illustrative comparative risks* (95% CI) | Relative effect | No of participants | Quality of the evidence | Comments | |
| Assumed risk | Corresponding risk | |||||
| Placebo | Vitamin E (capsules 2000 IU/day in 2 divided doses) | |||||
| Cognitive function Scale from: 0 to 70 Follow‐up: 6 to 48 months | The LS mean change from baseline in cognitive function in placebo group was 7.78 | The LS mean change from baseline in cognitive function in the intervention group was 1.81 lower | ‐ | 272 | ⊕⊕⊕⊝ | Higher scores represent worse cognitive function. A 4‐point difference in ADAS‐cog has been considered the MCID. |
| Adverse events Number of participants reporting ≥ 1 serious adverse event Follow‐up: 6 to 48 months | 625 per 1000 | 538 per 1000 | RR 0.86 | 304 | ⊕⊕⊕⊝ | ‐ |
| Deaths Number of deaths Follow‐up: 6 to 48 months | 204 per 1000 | 171 per 1000 | RR 0.84 | 304 | ⊕⊕⊕⊝ | ‐ |
| Activities of daily living Scale from: 0 to 78 Follow‐up: 6 to 48 months | The LS mean change from baseline in activities of daily living in the placebo group was ‐16.96 | The LS mean change from baseline in activities of daily living in the intervention group was 3.15 higher | ‐ | 280 | ⊕⊕⊕⊝ | Higher scores represent better activities of daily living. |
| *The basis for the assumed risk (e.g. the median control group risk across studies) is provided in footnotes. The corresponding risk (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). ADAS‐Cog: Alzheimer Disease Assessment Scale ‐ Cognitive Subscale; ADCS‐ADL: Alzheimer's Disease Cooperative Study/Activities of Daily Living Inventory;CI: confidence interval; LS: least square; MCID: minimum clinically important difference; RR: risk ratio. | ||||||
| GRADE Working Group grades of evidence | ||||||
| 1Quality downgraded one level due to imprecision. Evidence from a single study of modest size. This is supported by dichotomous data not reaching the optimal information size criterion (assuming α of 0.05, and β of 0.2) (Guyatt 2011). | ||||||
| Vitamin E (capsules 2000 IU/day in 2 divided doses) compared to placebo for people with mild cognitive impairment | ||||||
| Patient or population: people with mild cognitive impairment | ||||||
| Outcomes | Illustrative comparative risks* (95% CI) | Relative effect | No of participants | Quality of the evidence | Comments | |
| Assumed risk | Corresponding risk | |||||
| Placebo | Vitamin E (capsules 2000 IU/day in 2 divided doses) | |||||
| Progression to Alzheimer's disease Number of people progressing to AD Follow‐up: 36 months | 284 per 1000 | 293 per 1000 | RR 1.03 | 516 | ⊕⊕⊕⊝ | ‐ |
| Cognitive function Mean change from baseline of ADAS‐Cog Scale from: 0 to 70 Follow‐up: 36 months | Not possible to extract data for analysis. | ‐ | Not possible to extract data for analysis. | Unable to evaluate quality of evidence. | Uncertainty about how missing data were handled. Study reports no significant difference between intervention and control groups. | |
| Adverse events Number of participants reporting ≥ 1 serious adverse event. Follow‐up: 36 months | Not possible to extract data for analysis. | ‐ | 516 | Unable to evaluate quality of evidence. | Overall adverse event rates not reported. | |
| Death Number of deaths over 36 months Follow‐up: 36 months | 19 per 1000 | 19 per 1000 | RR 1.01 | 516 | ⊕⊕⊕⊝ | ‐ |
| Activities of daily living Mean change from baseline using the ADCS Scale from: 0 to 53 Follow‐up: 36 months | Not possible to extract data for analysis. | ‐ | Not possible to extract data for analysis. | Unable to evaluate quality of evidence. | Uncertainty about how missing data were handled. Study reports no significant difference between intervention and control groups. | |
| *The basis for the assumed risk (e.g. the median control group risk across studies) is provided in footnotes. The corresponding risk (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). ADAS‐Cog: Alzheimer Disease Assessment Scale ‐ Cognitive Subscale; ADCS‐ADL: Alzheimer's Disease Cooperative Study/Activities of Daily Living Inventory;CI: confidence interval; RR: risk ratio. | ||||||
| GRADE Working Group grades of evidence | ||||||
| 1Quality downgraded one level due to imprecision. Evidence from a single study of modest size. This was supported by dichotomous data not reaching the optimal information size criterion (assuming α of 0.05, and β of 0.2) (Guyatt 2011). | ||||||
| Outcome or subgroup title | No. of studies | No. of participants | Statistical method | Effect size |
| 1 Alzheimer's Disease Assessment Scale ‐ Cognitive subscale (ADAS‐Cog) (least square (LS) mean change from baseline at 6 to 48 months): completers Show forest plot | 1 | 272 | Mean Difference (IV, Random, 95% CI) | ‐1.81 [‐3.75, 0.13] |
| 2 Alzheimer's Disease Cooperative Study/Activities of Daily Living (ADCS‐ADL) (LS mean change from baseline at 6 to 48 months): completers Show forest plot | 1 | 280 | Mean Difference (IV, Fixed, 95% CI) | 3.15 [0.07, 6.23] |
| 3 Deaths (number of deaths over 48 months) Show forest plot | 1 | 304 | Risk Ratio (M‐H, Fixed, 95% CI) | 0.84 [0.52, 1.34] |
| 4 Serious adverse events (number of participants reporting ≥ 1 serious adverse event over 48 months) Show forest plot | 1 | 304 | Risk Ratio (M‐H, Fixed, 95% CI) | 0.86 [0.71, 1.05] |
| 5 Neuropsychiatric Inventory (NPI) (LS mean change from baseline at 6 to 48 months): completers Show forest plot | 1 | 280 | Mean Difference (IV, Fixed, 95% CI) | ‐1.47 [‐4.26, 1.32] |
| 6 Mini‐Mental State Examination (MMSE) (LS mean change from baseline at 6 to 48 months): completers Show forest plot | 1 | 273 | Mean Difference (IV, Fixed, 95% CI) | 0.19 [‐0.72, 1.10] |
| 7 Adverse events (number of participants reporting ≥ 1 adverse event over 48 months) Show forest plot | 1 | 304 | Risk Ratio (M‐H, Fixed, 95% CI) | 1.02 [0.85, 1.23] |
| Outcome or subgroup title | No. of studies | No. of participants | Statistical method | Effect size |
| 1 Progression to Alzheimer's disease (AD) (number of people progressing to AD by 36 months) Show forest plot | 1 | 516 | Risk Ratio (M‐H, Fixed, 95% CI) | 1.03 [0.79, 1.35] |
| 2 Deaths (number of deaths over 36 months) Show forest plot | 1 | 516 | Risk Ratio (M‐H, Fixed, 95% CI) | 1.01 [0.30, 3.44] |
