Description of the condition
Dementia is a clinical syndrome in which functional independence is compromised due to intellectual and cognitive impairment (mostly of gradual onset). It is typically caused by age-related pathophysiological processes. Alzheimer's disease (AD) and mixed AD and cerebrovascular disease are the most common causes of dementia in older people (Alzheimer's Association 2018). Other common causes include Lewy-body pathology (in dementia with Lewy bodies (DLB) and Parkinson’s disease dementia (PDD)) and frontotemporal lobar degeneration (in the frontotemporal dementias (FTD), and there are numerous other, rarer causes) (Alzheimer's Disease International 2009).
Dementia due to most neurodegenerative conditions is usually associated with aggregates of folded or misfolded proteins (Villemagne 2018). In the case of dementia due to AD, this includes aggregates of the Aβ protein that form into plaques in the space between neurons, as well as aggregates of misfolded tau protein that form neurofibrillary tangles inside neurons. Other protein-aggregates are implicated in other neurodegenerative disease (e.g. TDP-43 in FTD, alpha-synuclein protein aggregates in dementia with Lewy bodies). Aggregated proteinopathies usually spread in a predictable and well-described manner through cortical and subcortical regions (Braak & Braak 2012). In the case of most dementia aetiologies, the pathophysiological chain of events commences years or even decades before the onset of obvious clinical symptoms, at which stage individuals are increasingly brought to clinical attention (Alzheimer's Association 2018).
Regardless of cause, dementia usually has an insidious onset and progressive course (although in some cases, e.g. vascular cognitive impairment, a more rapid onset may be seen) (Wilson 2012). While the clinical presentation in the early or mild stages may vary according to the underlying disease aetiology, global cognitive impairment, changes in personality and behaviour, and compromised functional independence are common characteristics with clinical progression. Cognitive impairment (in the case of AD and vascular disease) and behavioural, personality, or language changes (in the case of frontotemporal neurodegeneration) are typically present well before a clinical diagnosis is made, but in the early stages these can be difficult to differentiate from common age-related changes or from symptoms associated with common psychiatric conditions (e.g. depression), a factor that often leads to delays in bringing the situation to medical attention. During the pre-dementia phase, individuals usually present with mild cognitive impairment (Albert 2011; Petersen 2004), a period in which cognitive impairment can be detected on formal examination, but there is usually no, or only minimal, impairment in the ability of the individual to carry out most activities of daily living. In the mild to moderate stages of dementia, cognitive impairment becomes more profound and widespread, functional disability becomes increasingly evident — particularly in relation to more complex activities — and caregiver burden tends to significantly increase (Berger 2005; Gaugler 2000). In the more advanced stages of dementia, most cognitive and functional abilities are profoundly impaired, and behavioural changes such as apathy, depression, aggression and agitation are frequently observed (Förstl 1999).
Despite some overlap, the cognitive symptom signature that characterises the different disease aetiologies that tend to develop into dementia can often be distinguished, at least in the early stages. In the case of dementia due to AD, the earliest cognitive signs on formal neuropsychological examination are almost invariably related to episodic memory function. Within the memory domain, the most striking deficits are usually observed on measures of new learning and delayed recall, deficits which precede the diagnosis of AD by several years (Weintraub 2012). Once deficits on measures of learning and memory have developed, individuals often show increasing difficulty performing tasks related to semantic memory, language, executive functions, and visuospatial/constructional abilities. In dementia with Lewy bodies, early cognitive impairments are more likely to involve striking visuospatial deficits, fluctuating attention and reduced working memory capacity, and the development of vivid hallucinations. In dementias related to frontotemporal lobar degeneration, early symptoms may be predominantly behavioural and related to social cognition in behavioural-variant FTD, or involve predominantly language skills and verbal expression in the temporal subtypes (Weintraub 2012). Although impaired performance on measures of episodic memory is also central to vascular dementia, people with this condition typically display a more striking deficit on executive and attention tasks, as well as on measures of semantic knowledge and visuospatial function (Graham 2004).
Dementia is highly prevalent in older people, is a leading cause of disability worldwide, and is associated with enormous financial, emotional, and societal burden (Wimo 2017), making research in this area a global priority (World Health Organization 2012). Despite years of research and numerous clinical trials, no cure is yet available for any of the irreversible causes of dementia. Cholinesterase inhibitors remain the primary pharmacological treatment for the cognitive symptoms in AD and related dementias; however, the effects of these drugs are not universal and are always temporary (Birks 2006). A range of non-pharmacological interventions (NPIs) that target different aspects of the clinical syndrome, associated disability and caregiver burden are available (for a comprehensive systematic review, see Olazaran 2010). NPIs are generally not disease-specific and do not directly engage underlying biological targets, and are therefore not 'disease-modifying'. On the other hand, NPIs are more likely to target a broader spectrum of clinically meaningful outcomes, and are less likely to cause adverse reactions. Within the broad category of NPIs, cognition-oriented treatments, and particularly cognitive training, have been the subject of much interest among researchers, clinicians, and the general public.
Description of the intervention
"Cognition-oriented treatments" (COTs), referred to previously as "cognition-focused interventions" (Clare 2002; Clare 2004), is an umbrella term referring to a group of NPIs in which a range of techniques are applied in order to engage thinking and cognition with various degrees of breadth and specificity. Unlike NPIs that are primarily oriented toward outcomes which are behavioural (e.g. wandering), emotional (e.g. anxiety) or physical (e.g. sedentary lifestyle), in COTs the goals include improving or maintaining cognitive processes or addressing the impact of impairment in cognitive processes on associated functional ability in daily life (Bahar-Fuchs 2013; Clare 2004). Cognitive training (CT), sometimes described in the literature as 'brain training', 'retraining' or 'remediation') typically involves guided practice of a set of structured — and usually standardised — tasks, designed to train relatively well-defined cognitive processes and abilities such as speed of information processing, attention, memory, or problem-solving (Bahar-Fuchs 2013; Mowszowski 2010). Other COTs described in the literature include cognitive stimulation therapy (CST), and cognitive rehabilitation (CR), and these approaches are regarded as distinct in terms of their underlying theoretical assumptions, core elements, and the contexts or populations in which they have been traditionally applied, but it is acknowledged that some overlap exists and that differentiating between these approaches is not always straightforward (Bahar-Fuchs 2013; Gates 2014). Indeed, these terms have been and continue to be applied somewhat interchangeably in the literature (e.g. Fernandez-Prado 2012; Giordano 2010), despite the availability of broad definitions and descriptions of these distinct forms of intervention (Bahar-Fuchs 2013; Clare 2004; Woods 2012). Table 1, below, summarises key defining features and common properties of these approaches. Cognitive stimulation is the focus of a separate Cochrane Review, which concluded that general cognitive stimulation consistently produces improvements in general cognition and, in some cases, in self-reported quality of life and well-being, primarily for people with mild to moderate dementia (Woods 2012). Cognitive rehabilitation, which is an inherently individualised approach emphasising collaborative goal-setting and a functional orientation (Bahar-Fuchs 2016; Clare 2001), has been considered alongside CT in previous versions of this Cochrane Review (Bahar-Fuchs 2013; Clare 2004); however, as the body of evidence for this approach has increased in recent years, and as it involves different methods and targets different outcomes, it will be considered in a separate Cochrane Review and the current review will accordingly focus only on CT.
Cognitive training is historically couched within the broader field of neuropsychological rehabilitation of individuals with brain injury and neurological diseases, with efforts to systematically retrain specific cognitive functions originally described by clinical researchers such as Leonard Diller and Yehuda Ben-Yishay in their pioneering work with victims of stroke and head trauma throughout the 1970s (Ben-Yishay 1978; Diller 1974). In the early 1980s, the principles of CT began to be applied in cognitively healthy older adults with subjective cognitive complaints (e.g. Zarit, 1981), however it was not until the late 1980s that cognitive training was first attempted with people with dementia (e.g. Beck 1988). A central assumption underlying cognitive training is that practice has the potential to improve or at least maintain functioning in the given cognitive domain. A further important assumption is that any effects of practice will generalise beyond the immediate training context. In other words, improved performance on a given task should lead to improved performance on other, related tasks that depend on the same cognitive process or ability. Although this last assumption has not often been supported by the evidence (Owen 2010; Papp 2009), some have argued that failure to produce transferable benefits is related in part to problems with task design (Jaeggi 2010). As noted above, CT traditionally involves the repeated practice of a set of structured tasks designed to target particular cognitive processes and abilities. Some authors have proposed that cognitive training should be divided into subtypes of cognitive exercise, and strategy training (Gates 2011), which involves instruction and practice in the use of specific cognitive strategies designed to further enhance performance, or minimise the impact of impaired cognition (e.g. method of loci, visual imagery) (Hampstead 2016). Cognitive training is different to the type of skill training often exercised by occupational therapists in that the target is usually an underlying process or ability, rather than a specific skill. While early versions of CT tended to be delivered in an inflexible 'one size fits all' approach, technological developments are leading to increasing tailoring of training focus based on individual cognitive profile and adaptive difficulty level in recent years (Bahar-Fuchs 2017; Peretz 2011). Cognitive training may be offered through individual sessions (Davis 2001; de Vreese 1998a; de Vreese 1998b Farina 2002; Koltai 2001; Loewenstein 2004), or group sessions (Cahn-Weiner 2003; Ermini Fuenfsch 1995; Kesslak 1997; Koltai 2001; Moore 2001), or may be facilitated by family members with therapist support (Neely 2009; Quayhagen 1995a; Quayhagen 2000). Initially delivered mainly in paper-and-pencil formats, computerised cognitive training (CCT) programmes have largely replaced more traditional methods over the past two decades (Davis 2001; de Vreese 1998; Quayhagen 1995; Quayhagen 2000). In some cases, the tasks or activities which form the focus of practice/training are analogues of actual daily activities, such as doing online shopping or setting up a dinner table (Farina 2002; Loewenstein 2004; Neely 2009; Zanetti 1994; Zanetti 1997; Zanetti 2001), and in these cases the distinction between cognitive training and functional skills training becomes more difficult. Skills-oriented interventions in which the target task is well structured, broken into relatively well-defined underlying cognitive performance elements, and where the outcomes of interest are cognitive processes rather than merely the performance of the intervention task itself (e.g. Neely 2009), appear to fit the conceptual framework of cognitive training. Conversely, where the focus of the intervention is a specific skill and there is no expectation to improve an underlying cognitive ability/process, and where the cognitive underpinnings are unclear or only vaguely addressed, the intervention might be best classified as ‘functional skills training’. In accordance with the suggestion that cognitive training may enhance the effects of pharmacological therapy (Newhouse 1997), some studies have evaluated the efficacy of cognitive training in combination with the use of cholinesterase-inhibitors (Cahn-Weiner 2003;de Vreese 1998a; de Vreese 1998b Loewenstein 2004), or other medications (Heiss 1993; Yesavage 1981).
|Table 1. Selected characteristics of cognitive training, stimulation, and rehabilitation|
|Cognitive training||Cognitive rehabilitation||Cognitive stimulation|
|Target||Impairment||Participation restriction||Participation restriction|
|Context||Structured tasks and environments||In the person’s natural environment||Usually in 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||A 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||Improve overall orientation and engagement in pleasant abilities|
How the intervention might work
Cognitive training aims to improve or maintain specific cognitive processes or global cognitive ability, and when used as an intervention approach with clinical populations, there is also an expectation that improvements in cognition will generalise to improvements in functional outcomes. Much has been written about the lack of unifying theories in the field of NPIs, including in relation to interventions aimed at changing behaviour (Michie 2008), cognition and function (Wilson 2002), and in relation to rehabilitation in general (Hart 2014). Indeed, no single theory exists that comprehensively explains such issues as why or how cognitive training should lead to improved cognitive and functional outcomes, whether and why some cognitive domains are more likely to respond to training than others, whether training should target single or multiple cognitive domains, or whether it should focus on improving impaired functions or building on preserved ones. To various extents, cognitive training interventions in healthy and in clinical populations draw instead on a range of theories and discoveries grounded in cognitive neuroscience (e.g. Jaeggi 2008; Sohlberg 1987), clinical practice and rehabilitation of patients with neurological injuries and diseases (Stuss 1999; Ponsford 2012), and continues to be shaped in response to relevant technological developments including in the gaming industry (Anguera 2015). Unfortunately, many cognitive training interventions have been and continue to be developed without clear reference to any relevant theoretical work.
A central assumption held by many advocates of cognitive training is that training an underlying cognitive ability or process will lead to generalised improvements that go beyond the training context (Lampit 2014). In cognitively healthy younger and older adults, and to a lesser extent, in individuals with mild cognitive impairment (MCI), there is little doubt that CT leads to improvements on trained or 'criterion' tasks. However, in both healthy and clinical populations, the evidence concerning learning transfer remains mixed, and the issue is hotly debated, with much of the debate concerning the identification of barriers and enablers of transfer of gains to untrained tasks that reflect the cognitive domain targeted by the training (near transfer) and other untrained cognitive domains as well as non-cognitive outcomes (far transfer) (Jaeggi 2010). In a recent comprehensive review and critique of the commercial cognitive training industry, Simons and colleagues point out that the discussion concerning transfer of learning can be traced back to very early theoretical accounts (Simons 2016), such as the so-called formal discipline theory, and the theory of transfer by identical elements proposed by Edward Thorndike in the early 20th century. It is beyond the scope of this review to cover these in detail, but a critical discussion of these accounts in relation to the cognitive training literature and industry is included in the review by Simons and colleagues (Simons 2016). Contemporary empirical findings suggest that factors that appear to be implicated in cognitive training-related gain-transfer include the degree of similarity or overlap in elements of trained and transfer tasks, extent of actual gain on trained tasks, baseline cognitive abilities, and age (Zinke 2014).
In addition to theories of learning and transfer, knowledge and expertise related to brain-behaviour relationships — as well as of mechanisms of injury, disease and recovery — are critical in informing the development of COTs, including cognitive training, in the context of work with persons with acquired disorders of the central nervous system (including traumatic brain injury, stroke and neurodegenerative conditions). Historically, such interventions have reflected two broad conceptual frameworks for the recovery of function after brain illness or injury: a restorative approach, and a contextualised or compensatory approach (Ylvisaker 2002). Techniques usually associated with cognitive rehabilitation, such as optimising residual cognitive abilities in impaired domains and making the most of unimpaired cognitive abilities, lend themselves more to compensatory approaches (Clare 2001b). In contrast, techniques usually associated with CT, such as the repeated exercise of standardised cognitive tests of increasing difficulty, and the targeting of specific cognitive domains, tend to reflect restorative principles and “thrive on the lure of neuroplasticity” (Rabipour & Raz 2012). Indeed, a range of neuroplasticity-related observations in animal and human studies, including changes at the molecular, synaptic, structural, and functional level associated with enriched environments and a structured training programme, are routinely cited as the proposed mechanisms of action in cognitive training (Valenzuela 2012). In recent years, growing evidence has shown that cognitive training is associated with changes in patterns of neural activation in key brain regions in healthy older adults (Belleville 2014), and in people with MCI (Belleville 2011; Hampstead 2011). Such increased brain activation may be the result of processes of synaptic growth and repair triggered by repeated practice on standardised tests.
Why it is important to do this review
The Alzheimer's disease drug development pipeline is slow and trials of disease modifying treatments have generally failed to produce improvements in any clinically-meaningful outcomes, despite succeeding in disrupting targeted pathophysiological processes (Cummings 2014; Cummings 2016; Salomone 2012), leading some to question the relevance of the dominant amyloid cascade hypothesis when it comes to the development of an effective treatment for dementia as a clinical syndrome (D'Alton 2011). NPIs aimed at developing ways for living better with dementia, in part by targeting relevant clinical outcomes and caregiver burden, are assuming an increasingly central role in the management of dementia and are recognised as an important adjunct, and even alternative, to available pharmacological treatments. A recent Lancet Commission on Dementia Prevention, Intervention, and Care argues that some NPIs can already play an important role in managing some of the cognitive, behavioural and neuropsychiatric symptoms of dementia, and points to the positive findings for cognitive stimulation therapy and the preliminary supportive evidence on cognitive rehabilitation (Livingston 2017).
In healthy older adults (Edwards 2017; Lampit 2014), and in persons with MCI (Chandler 2016; Hill 2017), systematic review findings on the effects of cognitive training on cognitive and several non-cognitive outcomes have been generally encouraging, and factors associated with increased intervention efficacy in CT are becoming better understood. Indeed, in recently published clinical practice guidelines for MCI, cognitive training has been classified as having Level C evidence, meaning that clinicians may recommend this form of intervention (Petersen 2018).
In contrast, most systematic reviews of CT for persons with dementia have to date produced largely negative findings (e.g. Bahar-Fuchs 2013; Hill 2017; but see Sitzer 2006). Our previous Cochrane Review of CT for persons with dementia included 11 randomised controlled trials, but there was no evidence to support CT in relation to any of the examined outcomes. We noted, however, that the certainty of these findings may be reduced by the relatively small number of highly heterogenous studies, which were often of low methodological quality. Against the background of a heavily divided scientific community, and an ever growing industry of commercial CT products that have at times made highly misleading claims, it is vital that clinicians, policy-makers, and the general public are presented with up-to-date, rigorous and unbiased review of the current literature on cognitive training for persons with mild to moderate dementia.