Review

For reprint orders, please contact: [email protected] Exercising the to avoid cognitive decline: examining the evidence

William E Reichman†1, Alexandra J Fiocco2 & Nathan S Rose3 and related cognitive disorders of the brain are strongly age-associated and prevalence is expected to rise dramatically with a rapidly aging population. As a result, there has been increasing on the prevention and treatment of cognitive decline associated with these conditions. A number of approaches have been designed to maintain and strengthen the cognitive capacity of the healthy, as well as the pathologically damaged brain. Evidence suggests that despite advancing age, our , and thus our cognitive functions, retain the ability to be maintained and strengthened through the biological process of . With this opportunity, a new commercial field of ‘brain fitness’ has been launched to bring to the market training exercises and games that maintain and strengthen cognitive abilities in adulthood. However, the majority of brain fitness methods and products now marketed and sold to consumers have scant scientific evidence to support their effectiveness.

Rationale behind brain exercise to avoid deficits, such as mild cognitive impairment and cognitive decline , remains controversial and is the cen- Increasing attention is being paid to the health, tral subject of this article. Despite this caveat, social and economic challenges and oppor­ ongoing scientific advances in various research tunities posed by a rapidly aging population. fields do support the potential for neural connec- In recent decades, given the projected expan- tivity to be malleable throughout the lifespan. sion of the number of individuals who will Specifically, enhanced understanding of the bio- develop dementia, it is becoming increasingly logical process of neuroplasticity and a retained important to develop comprehensive approaches capacity in late life for neurogenesis may provide to primary, secondary and tertiary prevention the rationale for the continued development of of dementia and related disorders. As the nor- training techniques to maintain and strengthen mal aging process is also strongly associated cognitive performance at any age. As a result, with brain changes that lead to a weakening of the scientific-based potential of ‘cognitive exer- some select cognitive domains in healthy per- cise’ and the accompanying era of a commercial sons, there has been growing interest in finding ‘Brain Fitness’ marketplace have most certainly methods to ‘keep our brains sharp’ by main- now arrived. 1Baycrest Centre, Department of taining or enhancing cognitive performance [1]. Psychiatry, Faculty of Medicine, In addition, as age is the pre-eminent risk fac- Normal & pathological cognitive aging University of Toronto, 1 Kings College Circle, Toronto, ON, M5S 1A8, Canada tor for the development of pathological brain Over the last few decades, a large body of 2Kunin-Lunenfeld Applied Research alterations giving rise to dementia, there is an research has been conducted to identify those Unit, Baycrest Centre, 3560 Bathurst St, Toronto, ON, M6A 2E1, Canada increasing focus on prevention and treatment changes in that represent the normally 3Rotman Research Institute, Baycrest including the use of techniques that maintain or aging brain by contrast to those that may be Centre, 3560 Bathurst St, Toronto, ON, M6A 2E1, Canada strengthen cognition [2]. Not surprisingly, inter- evidence of brain pathology [3]. The areas of cog- †Author for correspondence: est among the consumer public in learning how nition that are often examined in this context Tel.: +1 416 785 2500 to prevent cognitive loss and how to strengthen include , language, visuospatial ability, Fax: +1 416 785 2464 [email protected] cognitive abilities in mid and later life appears speed of information processing, attention and to be steadily rising. This has led to the emer- executive functioning. To assess these different gence of a new ‘Brain Fitness’ commercial indus- domains, neuropsychologists use a broad port- try in which structured, live cognitive training folio of testing paradigms that tap into various Keywords programs, computerized games, internet-based cognitive functions. As it is beyond the scope • aging • brain • cognition course work and other ‘products’ are being of this article to review these specific methods, • exercise • fitness marketed and sold to consumers [1]. Whether there are a number of very comprehensive refer- these and other activities have been rigorously ences for the interested reader [4]. Despite the and reliably demonstrated to enhance cognitive conclusions that have been drawn from the liter- part of skills and functional abilities in healthy adults as ature in normal aging and cognition, it is impor- well as individuals with severe acquired cognitive tant to recognize some caveats. The majority of

10.2217/AHE.10.54 © 2010 Future Medicine Ltd Aging Health (2010) 6(5), 565–584 ISSN 1745-509X 565 review – Reichman, Fiocco & Rose

research in this area has been cross-sectional in most common form appearing in the literature nature, comparing one age group’s performance is the MCI-amnestic subtype (aMCI) [7]. This to another. Any differences between younger represents a disturbance of memory with little versus older participants could be in part, owing to no other cognitive impairment and has shown to cohort-specific effects. Further longitudinal to be a significant risk factor for the eventual research involving specific age cohorts would be development of dementia. Many researchers informative in this regard. In addition, much of believe aMCI to be a prodromal condition of the data reported to support age-related changes Alzheimer’s disease (AD) [8]. in cognition describe mean group differences in test performance. However, great individual Dementia variability in cognitive ability is often seen Dementia is a syndrome of acquired and per- within specific age groups. sistent decline in memory and other realms of cognitive performance leading to functional dis- Normal aging & cognition ability. The most common cause of dementia Different types of cognitive abilities tend to be is AD, accounting for approximately 50–75% grouped into categories or domains which vary of all cases [2]. However, postmortem stud- in the extent of age-related change. Table 1 pro- ies suggest that many cases are in fact ‘mixed vides a rough summary of age-related changes dementia’, a combination of AD and vascular in different domains of cognition. Although dementia. It is widely believed that cerebrovas- theorists debate about the amount of over- cular disease is the second most common cause lap between different cognitive abilities, some of dementia (vascular dementia). Other causes researchers have characterized a general pattern include dementia with Lewy bodies, frontotem- of age-related changes in cognition in terms of poral dementia, trauma, metabolic abnormali- crystallized and fluid intelligence[5] . Fluid intel- ties, nutritional deficiencies and infections of the ligence is the ability to analyze and solve novel CNS. A host of studies have demonstrated that problems, independent of acquired know­ledge. It dementia owing to AD may be prevented by includes problem-solving skills, abstract reason- cognitive stimulation, engagement in lei- ing, learning and , and is more sure activities, level of work complexity and susceptible to aging compared with crystallized educational attainment. intelligence (Cf) [6]. Cf refers to the ability to Whether these three states of cognitive func- use acquired skills and knowledge through edu- tion lie along a continuum remains to be elu- cational and cultural experiences. It includes the cidated. However, research demonstrates that ability to formulate general knowledge/informa- linear and nonlinear changes in various cog- tion, vocabulary, reading com­prehension, anal­ nitive domains, including verbal memory and ogies and the ability to reason using words and fluency, visuospatial abilities and psychomotor numbers. Whereas Cf is either stable with age speed, precede a diagnosis of MCI and dementia or may actually continue to improve over time, by several years [9,10]. Thus, if states of cognitive fluid intelligence may be especially vulnerable function do follow a continuum, at what point is to aging [6]. brain structure and function malleable? Although a number of cognitive domains have been characterized, fervent debate continues Brain plasticity & reserve theory regarding the distinction between the domains, Neurogenesis & neuroplasticity the type and magnitude of age-related changes Although once considered fixed and unable to experienced within each domain and the under- regenerate or reorganize, it is now well known lying mechanisms for such change. Regarding that cells in the adult rodent and mamma- pathological forms of aging, it is important to lian brain are dynamic and modifiable [11,12]. consider how different cognitive functions are Neurogenesis is the ability of the brain to gener- affected in similar ways as normal aging or ate new cells [11], whereas neuroplasticity refers whether certain functions are uniquely affected to the capacity of the brain to change physi- by disease. cal structure (i.e., reorganization of neuronal networks) and function in response to envi- Mild cognitive impairment ronmental attributes or factors [13]. The neu- Mild cognitive impairment (MCI) is an acquired robiological basis for the notion that we can disturbance in cognition without resultant impact (protect or enhance) cognitive func- impairment in daily functioning. While a vari- tion by modifying experience is rooted in the ety of subtypes of MCI have been described, the concept of neuroplasticity.

566 www.futuremedicine.com future science group Exercising the brain to avoid cognitive decline – Review Gf Cf Gf Cf Cf/Gf ) for semanticfor dementia) † ↓ = (possibly ↑ ( ↓ (laboratory-based tasks) = (possibly ↑ for real-world tasks) = primary/short-term ↓ working memory, especially visuospatial = = ↓ ↓ ↓ ↓ ↓ Effects of age NART, vocabularyNART, tests McDaniel and Einstein paradigm, virtual week Digit span, reading span, n-back or corsi blocks Priming performanceContinuous task Dual-task paradigms remember(e.g., words, monitor twofor odd digits presented in succession) Simple choice reaction time Pursuit rotor task, serial reaction time task, mirror tracing task or weather prediction task Cocktail party effect; reading with distraction CVLT, logical memoryCVLT, Common measures Recalling facts or the name of personsfamiliar Remembering take medication to or attend upcoming appointments Maintaining a phone number or mental arithmetic Read words (bone) and then complete word fragment (b_n_) with first word comes that to mind Monitoring the gas gauge or cookies the in oven Driving while conversing; performing a memory or attention task while monitoring digits Press a button when a stimulus appears How ride to or play piano a bike Listening your to friend and not the person at the next table Recalling the details recent of conversations or where you placed your keys yesterday Example Knowledge, facts and meanings Remembering perform to intended actions at the appropriate moment in the future; ‘remembering remember’ to Temporary maintenance and manipulation informationof Behavior affected the by past with awareness focusingConcentration, on relevant information and ignoring irrelevant information extended for periods time of Performing or switching between two tasks at the same time Motor or physical response Tacit knowledgeTacit or lack awareness of Motor memory Focusing on relevant information; ignoring irrelevant information Description The ability a person of or recite ‘declare’ to evidence memory of ability Recalling information about prior experiences, events and episodes Declines may be explained by undiagnosed preclinical dementia [78]. – – Prospective memory – Working memory – Implicit memory Vigilance Divided attention Processing speed Psychomotor speed Nondeclarative – Attention Selective attention 1. Description 1. Table of various cognitive domains and associated effects of age in adulthood. Domain Memory Declarative andCf reflect Gf tasks or abilities thought to capture respectively,Cf andGf, and are only included for those domains that clearly† fall into one or theother category. – Cf: Crystallized intelligence; California CVLT: verbal learning test; Gf: Fluid intelligence; NART: National adult reading test.

future science group Aging Health (2010) 6(5) 567 review – Reichman, Fiocco & Rose Gf Gf Gf Gf Gf Cf Gf Cf/Gf ) (i.e., ‘general slowing’), ‘general ↓ (i.e., especially visuospatial ↓ ↓ ↓ ↓ = (possibly ↑ ↓ Effects of age Lexical decision, mental rotation or enumeration Hanoi of Tower Wisconsin card sort matrices Raven’s Stroop test vocabulary,NART, reading comprehension Drawing, copying, assembling block designs, Hooper Visual Organization test Common measures Press yes if the letter string is a real word or no if it is a nonword Organizing a series steps of pick to up items from grocery store Playing complex video games first-person(e.g., shooters) Understanding analogies; solving problems Resisting dessert when trying to lose weight Read a book, write about it or talk about it Driving Example Description Processing information and making decisions as fast and as accurately as possible initiatePlan, and organize, sequence activities in the performance a of complex task Rapidly shift or change an approach a to task as the situation demands Higher order strategy and conceptual formulation, information manipulation and abstract thinking Interference or conflict resolution or withholding an inappropriate response Both expressive and receptive components and the ability write to and read Mental imagery, mental rotation, distance judgments or spatial/directional relations Declines may be explained by undiagnosed preclinical dementia [78]. Planning Mental flexibility Reasoning Inhibition language/visuospatial abilities Language (verbal) abilities Visuospatial abilities 1. Description 1. Table of various cognitive domains and associated effects of age in adulthood. Domain Processing speed (cont.). Information processing andCf reflect Gf tasks or abilities thought to capture respectively,Cf andGf, and are only included for those domains that clearly† fall into one or theother category. Cf: Crystallized intelligence; California CVLT: verbal learning test; Gf: Fluid intelligence; NART: National adult reading test.

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Neuroplasticity: evidence from by extension, cognitive training may be benefi- animal models cial in diagnosed dementia patients by improving Animal models provide a wealth of infor- or stabilizing cognitive function. mation on the neurobiological correlates of age-related brain dysfunction. Canine stud- Cognitive & brain reserve in humans ies demonstrate that the brains of aged dogs The concept of reserve refers to a threshold accumulate Ab, which correlates with cognitive model of vulnerability to injury or the cumula- impairment [14] and further display increased oxi- tive effects of aging. For example, there appears dative damage [15], decreased myelination [16] and to be significant variability among individuals neuronal loss in the [17]. Rodent in the clinical consequences and severity of dis- data suggest that corticocortical circuitry dete- ability associated with a similar level of patho- rioration may result from factors including logical burden within the brain [29]. This has demyelination [18], decreased neurotransmission been demonstrated in AD, stroke and traumatic (e.g., N-methyl-d-aspartate binding) [19] brain injury. Stern and collaborators have argued and endocrine dysregulation (e.g., of glucocor- that although the terms ‘brain reserve’ and ‘cog- ticoids or estrogen) [20,21]. Finally, monkey data nitive reserve’ are often used interchangeably, demonstrate age-related loss of spines on pyra- they each represent a different concept [30]. midal cells and decreased density of synapses in Specifically, in their framework brain reserve the , all of which correlate with refers to the physical endowment of the brain cognitive impairment [22] . in terms of cranial capacity (a proxy for brain Initial insight into the brain’s capacity of size), the density of neurons and the degree of neuro­plasticity stems from the plethora of ani- connectivity between them (synaptic density). mal research describing the effects that occur , on the other hand, refers in the brain of the adult rodent with the pro- to the potential to increase the efficiency and vision of a more complex living environment capacity of existing neural pathways and/or versus a simple cage. The ‘enriched environ- to recruit new pathways that are not typically ment’ is a large cage that includes items such as used to accomplish a task. Several perspectives toys, tunnels and a running wheel, all of which have been delineated to link theories of brain are considered to create cognitive stimulation. and cognitive reserve. One perspective is that of Studies show that environmentally enriched computational redundancy and flexibility[31] ; an adult rodents display an increase in brain syn- individual with high reserve will display more aptic density and numbers of synapses, enlarged flexible cognitive processes (i.e., high cognitive dendritic length, increased dendritic branching reserve) and a greater number of redundant neu- and the creation (neurogenesis) and matura- ral pathways (i.e., high brain reserve) and thus, tion of new neurons and connections [23,24]. will experience a longer asymptomatic period Presumably, several of these changes are medi- despite neurological insult. Furthermore, two ated by environment-induced increases in neu- individuals with the same level of brain reserve rotrophic factors including brain derived neu- may display differential symptoms follow- rotrophic factor and nerve growth factor [13,23]. ing brain insult depending on complexity and Correlated with these changes is enhancement flexibility of their cognitive processes. of the rodent’s motor and cognitive performance. Thus, the greater the degree of anatomical The effect of has brain reserve that exists, the higher the threshold also been tested in transgenic mice models of of pathological burden that needs to be crossed AD. Following a 30-day enriched housing study, before brain changes are significant enough to Herring and colleagues found that transgenic lead to clinical features of illness (i.e., cogni- CRND8 mice that initially display reduced tive impairment). It has been demonstrated neurogenesis compared with wild-type mice that brain reserve can be influenced and is not exhibited enhanced cell proliferation and neu- merely fixed: a variety of studies have demon- rogenesis in the hippocampus [25]. Other studies strated that aerobic physical exercise leads to have demonstrated improvements in cognitive morphological changes such as increased brain function with reductions in Ab plaque burden volume within the rodent as well as the adult and amyloid angiopathy following enriched human [32]. It is less clear whether cognitive living [26,27], and reductions in hyperphos­ exercises can induce the same type of struc- phorylated tau and oligomeric Ab, two hall- tural alterations. However, Stern and colleagues marks of AD [28]. These studies highlight the have posited that intellectually enriching possibility that environmental enrichment, and activities throughout life (education, mentally

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challenging work and certain leisure activi- The greatest degrees of complexity of work that ties) and perhaps, as well, structured cognitive involved analyzing, coordinating and synthesiz- training could enhance cognitive reserve [33]. ing data was associated with reduced dementia As a consequence, cognitive reserve could theo- risk, even among lower educated participants retically modulate the potential impact of age- (relative risk: 0.52; 95% CI: 0.29–0.95). related and pathological brain changes on cog- Wilson and colleagues studied the rela- nitive performance. A number of human studies tionship between participation in cognitively have addressed whether enhancement of reserve stimulating activities that involved information is possible through cognitive exercise. The fol- processing and the risk of incident dementia in a lowing section of the article reviews studies cohort of older Catholic nuns, priests and broth- that have assessed whether cognitive training ers without dementia at baseline [36]. Assessment techniques can enhance cognitive function and of cognitive activity used frequency of engage- possibly alter reserve in later years. ment in common pursuits including viewing tel- evision, listening to radio, reading newspapers, Protecting brain health in late life: magazines and books, playing games such as epidemiological evidence cards, checkers, crosswords and other puzzles, A number of studies have examined how par- and visiting museums. Proportional hazards ticipation in mentally stimulating activities model demonstrated that a one point increase throughout adult life can protect cognitive in cognitive activity score was associated with function in older age through impacting brain a 33% reduction in risk for AD (hazard ratio: reserve, cognitive reserve or both. These stud- 0.67; 95% CI: 0.49–0.92). In their ana­lysis of ies can be grouped into two types based on additional random-effects models, they reported their design: observational and experimental. that a one point increase in cognitive activity Findings of both types of studies have provided was associated with reduced decline in global support for the development of efforts to further cognitive function by 47%, working memory by methodically strengthen cognition through for- 60% and perceptual speed by 30%. The authors mal interventions. First, we review epidemiologi- concluded that on average, a person reporting cal evidence for the potential of various lifestyle frequent cognitive activity at baseline (90th per- factors to protect brain health in late life. Table 2 centile) was 47% less likely to develop AD than a summarizes the epidemiological studies reviewed person with infrequent activity (10th percentile). below. Verghese and colleagues studied whether In a longitudinal study evaluating the relation- participation in leisure activities reduced the risk ship between engagement in cognitive demand- of incident dementia in community-residing ing activities and the degree of cognitive decline older adults [34]. The authors found that leisure experienced over time, Wilson and colleagues activities such as reading, playing board games, reported on a cohort of 4000 community resid- playing musical instruments and dancing were ing older adults [37]. The investigators reported all associated with a reduced risk of developing that more frequent cognitive activity was asso- dementia. Specifically, a one-point increment in ciated with reduced cognitive decline during a cognitive activity score was significantly asso- follow-up. Specifically, a one point increase in ciated with a reduced risk of dementia (hazard cognitive activity score was associated with an ratio: 0.93; 95% CI: 0.90–0.97). By contrast, a approximate 19% decrease in the annual rate of one-point increment in physical activity score cognitive decline. The authors concluded that was not associated with reduced incident demen- frequent participation in cognitively stimulat- tia. The authors concluded that controlled trials ing activities is associated with reduced cognitive are required to prospectively assess the effects of decline in older persons. cognitive leisure activities on the risk of demen- Fritsch and colleagues examined the relation- tia. Karp and coworkers reported on the asso- ship between participation in novelty-seeking ciation of work complexity during midlife and leisure activities and the risk for developing dementia risk after 75 years of age [35]. The inves- AD [38]. Using a case–control method, they com- tigators reported that lower dementia risk was pared the reports of surrogates of AD patients associated with complexity of work as measured (n = 264) with a control group of neighbors and by the use of workplace related data (relative risk: friends of the cases plus a randomly selected 0.85; 95% CI: 0.75–0.95) and engagement with group of community members (n = 545) regard- people (relative risk: 0.88; 95% CI: 0.29–0.95). ing prior participation in different types of men- However, the association was no longer statisti- tal leisure activities, especially those involving cally significant after controlling for education. ‘novelty seeking’. Factor ana­lysis of the activity

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Table 2. Epidemiological studies that assess the association between lifestyle factors and cognitive function in late life. Study Sample Lifestyle Statistically Follow-up Significant Generalization Ref. size (n) factors controlled factors (years) factors outcome assessed measures Verghese 469 healthy Cognitive activity, Age, sex, education, 5 Leisure factors Reduced risk [34] et al. older adults physical activity physical morbidity and (reading, playing of dementia baseline cognitive status games, musical instruments or dancing) Karp 931 healthy Occupation Education 6 More complex Reduced progression [35] et al. older adults complexity, social work and to dementia† engagement engagement with people Wilson 801 healthy Cognitive activity Age, sex, education and 4.5 Cognitive activity Reduced cognitive [36] et al. older adults (e.g., reading and baseline cognitive status (e.g., reading and decline and playing games) playing games) progression to dementia Wilson 4000 adults Cognitive activity Baseline level of 5.3 Cognitive activity Reduced cognitive [37] et al. (e.g., reading and cognition, age, sex, race (e.g., reading and decline (e.g., episodic playing games) and education playing games) memory, immediate and delayed recall or perceptual speed and the MMSE) Fritsch 809 adults Mental leisure Age, gender, –‡ Novelty seeking, Reduced risk [38] et al. (including activities (novelty ethnicity, education exchange of ideas of dementia 264 seeking, and occupation surrogates of exchange of ideas AD patients) and social activity) Helzner 283 AD Leisure activity Age, sex, ethnicity, 5 Intellectual activity Higher baseline [39] et al. patients education and cognitive status, baseline IQ fewer physical comorbidity (including stroke), but faster decline postdiagnosis †Effects were positive, but no longer significant after statistically controlling for education. ‡Data not available: a case–control method with logistic regression was used. AD: Alzheimer’s disease; MMSE: Mini-mental status exam. questions identified three activity factors of sig- Paradoxically, in a 5-year longitudinal study nificance: novelty seeking, exchange of ideas that assessed prediagnosis leisure activity on rate and social activity. Logistic regression ana­lysis of cognitive decline in patients with AD, Helzner indicated that greater participation in novelty- and colleagues reported that high leisure activ- seeking and exchange of ideas activities were sig- ity prior to AD diagnosis, especially intellectual nificantly associated with decreased odds of AD. activity, was associated with faster postdiagnosis The odds of AD were lower among those who cognitive decline [39]. Higher leisure activity was participated more often in activities involving associated with higher baseline cognitive func- the exchange of ideas (odds ratio [OR]: 0.695; tion, fewer medical comorbidities and lower 97.5% CI: 0.467–1.034) and were even lower stroke prevalence. Based on these and other for those participants who reported more fre- findings [40], the authors proposed that leisure quent participation in novelty-seeking activities activity serves as a proxy of cognitive reserve. (OR: 0.248; 97.5% CI: 0.139–0.443). Finally, With enhanced compensatory mechanisms at the investigators reported that participation in play, individuals who engage in high leisure social activities did not increase or decrease the activity may delay the adverse effects of AD asso- odds of being in the AD group. ciated pathology, allowing for a longer period of

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normal cognitive function [41]. However, once with a longitudinal follow-up [44]. Of the 54 the higher threshold of AD pathology is met, identified studies, only seven published trials quicker neurocognitive decline ensues [41,42]. involving approximately 3000 participants, Collectively, there is evidence for cognitive possessed eligible criteria for inclusion which reserve in late life in that higher cognitive func- included randomization, repetitive training over tioning in late adulthood is associated with a separate days for more than 1 week, longitudinal lifelong pursuit of complex cognitive activities. follow-up beyond 3 months and participation However, the studies reviewed above are cor- by healthy community-dwelling older adults relational in nature and therefore one cannot be of more than 50 years of age. Participants with certain of the causal role of cognitive activity. any cognitive impairment, including dementia Additional evidence from experimental studies were excluded, as were individuals with a major (ideally randomized clinical case–control trials) neurological or psychiatric disorder. The major provides an even more convincing case. Below, a search engines included MEDLINE, PubMed review of the relevant studies is reported. and key references. The studies examined in this review focused on techniques to improve Cognitive training approaches to cognitive performance in reasoning, memory, protect brain health in later life: information processing speed, problem-solving case–control studies and attentional ability. Many of the studies Two types of training approaches included a combination of both compensa- Two approaches towards cognitive training stud- tory and restorative types of cognitive training. ies have been taken, compensatory and restor- Pre- and post-intervention scores were integrated ative. Compensatory training approaches teach using a random effects weighted mean difference new ways to accomplish a cognitive task by work- (WMD) meta-analytic approach. The investiga- ing around cognitive weaknesses or deficits. This tors concluded that cognitive exercise training is done by training strategies such as categorizing in healthy older adults produces strong and per- or visualizing information that is to be remem- sistent protective effects on longitudinal neuro- bered, as well as utilizing external memory aids psychological performance, particularly in the such as notes, calendars or other environmen- domains that were of major focus for the inter- tal cues [43]. Restorative approaches seek to vention. The effect size was reported as strong strengthen specific cognitive domains in order for cognitive exercises compared with a control to improve functional performance more gener- condition (WMD: 1.07; 95% CI: 0.32–1.83; ally. For example, participants of some studies z = 2.78; n = 7; p = 0.006; n = 3;194). Far trans- practice memory and attention games with the fer was only reported in some of the studies. hope of improving those domains in general. The Notably, the authors concluded that although idea behind restorative training is that training cognitive exercise demonstrated protective on one task might enhance the cognitive ability effects on neuro­psychological function, it has or abilities that are needed to perform similar yet to be shown to prevent incident dementia. tasks (near transfer) or very different tasks such Papp and colleagues also reviewed the state as activities of daily living (far transfer). Whereas of the literature on immediate and delayed compensatory approaches tend to only produce effects of cognitive interventions in healthy eld- near transfer effects by benefiting the specific erly individuals [45]. Their review utilized five training task or domain that was targeted by electronic databases: MEDLINE, Scopus, the the training program, far transfer effects through Cochrane Collaboration, Dissertation Abstract restorative training are considered the ‘holy grail’ International, PsychINFO and two registers: because they suggest cognitive functions can be Current Controlled Trials and Clinicaltrials.gov. enhanced beyond the specific domain of train- Only studies that were randomized, written in ing. To date the training studies that have been English and published after 1992 were included conducted have used either compensatory or for evaluation. Study participants had to be restorative (or both) types of approaches to assess healthy community residing elderly. Using the impact of cognitive training on brain health. these criteria, ten studies met inclusion for their meta-ana­lysis. The authors found a post-training Cognitive training interventions in mean weighted effect size (Cohen’s d) of 0.16 healthy elderly: case–control studies (95% CI: 0.138–0.186), which represents a In a meta-ana­lysis of the cognitive exercise lit- small, but significant benefit of cognitive exer- erature, Valenzuela and Sachdev conducted a cise. However, they concluded that the exist- systematic review of randomized clinical trials ing literature is limited by a lack of consensus

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on what constitutes the most effective type of the memory or speed of information processing cognitive training, insufficient follow-up times, groups. However, all three groups maintained a lack of matched active controls and few out- the specific cognitive domain improvement comes demonstrating transfer of any cognitive initially reported at the beginning of the study. gains to daily function or global cognition. This Further, the booster training for speed of infor- ana­lysis also failed to detect any evidence that mation processing, but not for the other two cognitive training prevents the incident AD in groups, led to a significant performance-based healthy older adults. cognitive improvement. Included in both of the above analyses is the In summary, this study demonstrated that largest and perhaps most informative study ever specific-domain cognitive training, as com- carried out examining the long-term effects of pared with a control condition, improves ability cognitive training in healthy older adults: the in specific targeted domains, which persist for Advanced Cognitive Training for Independent at least five years in study completers. In terms and Vital Elderly (ACTIVE) study. It included of maintaining functional ability in IADLs, 2832 volunteer participants, with a mean age only reasoning training seems to have had this of 74 years and was conducted in multiple sites. specific positive effect. Wolinsky and colleagues Participants were recruited from senior hous- reported that the ACTIVE trial interventions ing, community centers, clinics and hospitals. also had a positive impact on well-being by miti- The intervention consisted of ten small group gating decline on health-related quality of life sessions designed to train one of three cogni- measures. Specifically, they reported that at the tive areas: memory, reasoning or processing 2-year follow-up, there was a protective effect speed [46–48]. Training sessions lasted 60–75 demonstrated by the speed of processing, but min each and were led by a certified trainer. The not for the memory or reasoning interventions. memory training sessions consisted of learning However, at the 5-year follow-up, all interven- mnemonic strategies (organization, visualization tion groups demonstrated a protective effect on and association) for recalling word lists and texts decline in health-related quality of life [49]. This (verbal material) followed by practice using those latter point is important because it suggests that, strategies. Reasoning training included learning unlike many medical treatment interventions, and practicing strategies for finding and com- participants in this cognitive training program pleting patterns in a letter/word series. Speed did not appear to experience any negative side of processing training involved learning how effects of treatment and some even appeared to to effectively visually search and divide atten- have experienced an enhanced quality of life. tion by doing challenging tasks on a computer Mahncke and colleagues conducted a study screen [46]. Participants were randomized into assessing the potential benefits of a computer- one of the three training groups or a fourth ized cognitive training program developed by a control group. In a random sample of those commercial entity, Posit Science [50]. The ‘exper- who completed initial training, four ‘booster’ imental’ group engaged in six computer-based training sessions were provided at 11 months exercises of increasing difficulty tied to gains in and 35 months. Assessments were conducted at performance using the Posit Science Program. baseline, immediately following the interven- This involved using the program in 1-h ses- tion and then at 1, 2, 3 and 5 years follow-up. sions, five-times per week for 8–10 weeks. The The immediate ACTIVE results demonstrated ‘active control’ group accessed a computer-based improved cognitive function in each of the educational program on how to maintain good three domains targeted for intervention. These cognitive health and were asked to recall what improvements were maintained through 2 years they had learned. The ‘no contact’ control group of follow-up, although no far transfer effects received no intervention. Compared with the were observed [48]. Willis and colleagues specifi- control groups, the experimental group demon­ cally reported data on the 5-year follow-up of the strated an immediate improvement in specifi- initial study [46]. Approximately two-thirds of cally trained cognitive domains including speed the original sample was available. As compared of processing and a variety of verbal memory with controls, those who had been randomized related tasks. to the reasoning training conditions had less In a larger follow-up investigation, Improve­ functional decline in self-reported instrumental ment in Memory with Plasticity-Based Adaptive activities of daily living (IADLs) at the 5-year Cognitive Training (IMPACT), Smith and mark (effect size: 0.29; 99% CI: 0.03–0.55). coworkers further reported on the efficacy of This effect on function was not seen in either the ‘Posit Science Brain Fitness Program’ in

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community residing older adults [51]. Participants patients meeting clinical criteria for mild AD, were randomly assigned to two groups: an experi- and 12 MCI patients allocated to a waiting list mental group and an active control group. The control condition. Both intervention groups experimental group used the Posit Science com- participated in a 4-week group format cogni- puterized training method while the active con- tive training regimen that included activity trol group used computers to view educational planning, training in self-assertiveness, stress programs on history, art and literature and then management, relaxation techniques and the use were quizzed after each training session on the of external memory aids, memory training and content of the programs. All participants endured physical exercise. The investigators reported 1 h of training per day, 5 days a week for a total that after four weeks, MCI participants dem- of 8 weeks. The investigators reported that on onstrated significant improvements on IADL, a standard of auditory verbal and nonverbal episodic recall and mood. memory and attention (RBANS auditory mem- However, participants with mild AD seemed to ory/attention), the experimental group dem- gain no measurable benefits from the program onstrated significant (p = 0.02) improvement other than an improvement in verbal memory, (3.9 points; 95% CI: 2.7–5.1) compared with which failed to reach statistical significance. The the active control group (1.8 points; 95% CI: MCI control participants demonstrated a signifi- 0.6–3.0). Therefore, the computerized training cant retest effect on verbal episodic memory, but method of Posit Science resulted in near transfer no other significant changes. It is promising that effects; however, it is unknown whether these individuals with MCI showed some response to were long-lasting effects or if there were any the training program, but owing to the multiple far transfer effects on more global or everyday factors that were trained, it is difficult to dif- cognitive functions. ferentiate between types of training that were In addition to enhancing cognitive perform- beneficial and those that were not. ance, Engviv and colleagues reported on the Troyer and colleagues conducted a rand- effects of an 8-week intensive memory training omized controlled trial to evaluate the effec- program on cortical thickness in older adult tiveness of a multidisciplinary group-based participants [52]. Compared with the controls, intervention program designed to change eve- memory trainers displayed increased cortical ryday ‘memory behavior’ in participants with a thickness of the right fusiform and lateral orbito­ MCI [54]. The active intervention consisted of frontal cortex, which were both correlated with evidence-based memory training techniques and improvement in source memory performance. lifestyle education consisting of ten 2-h small Although only short-term effects were exam- group sessions conducted over 6 months. The ined, these findings support the notion of neuro­ investigators reported that the active interven- plasticity in later life, and of enhanced brain tion group demonstrated an increase in mem- reserve following cognitive training. However, ory-strategy knowledge and use from pretest to longitudinal research is needed to determine the immediate post-test, and these gains were main- lasting effects of cognitive training on reserve. tained at 3-months post-test, relative to wait-list Although exciting prospects are emerging, controls. Notably, there were no group differ- more research is required to determine the most ences in memory beliefs or on neuropsychologi- effective type of cognitive training for protect- cal test measures of objective memory perform- ing cognitive function and producing transfer ance. The authors concluded that individuals to everyday life. With regards to cognitive train- with MCI can acquire and maintain knowledge ing interventions in populations associated with about memory strategies and can alter their daily pathological aging, the need for more research memory behavior by applying this knowledge is even greater. Table 3 summarizes the cognitive into everyday functioning. training studies on healthy aging as well as those Belleville and collaborators reported on the involving MCI and AD populations, some of efficacy of cognitive training in participants which are reviewed in detail below. with MCI and individuals with ‘normal cog- nitive aging’ [55]. The intervention consisted of Cognitive training interventions in MCI teaching the participants strategies to improve Kurz and colleagues explored the benefits episodic memory. Three tasks of episodic of a multicomponent cognitive rehabilita- memory (list recall, face–name association tion program in patients with MCI [53]. Their and text memory) were used as primary out- study included two active intervention groups come measures. The authors reported that, composed of 18 patients with MCI and ten relative to a wait-list control condition, the

574 www.futuremedicine.com future science group Exercising the brain to avoid cognitive decline – Review [51] [55] [53] [52] [50] [79] [48] [54] [46] Ref. Significantfar transfer effects ADL, IADL and driving habits questionnaire IADL Auditory memory and attention Not reported Volumetric changes in structural MRI ADL and mood MCI; in no change in AD Everyday memory strategy knowledge and multifactorialuse, memory questionnaire Subjective memory and well-being GDS Significant training and near transfer effects Domain of targeted training Domain of targeted training Attention, episodic memory, visuospatial abilities Attention, episodic memory, visuospatial abilities recognitionWord and source memory andVerbal nonverbal episodic memory in MCI; no change in AD Episodic recall, digit span and laboratory memory strategy use Episodic recall lists of and face–name associations Attention, episodic memory, visuospatial abilities and verbal fluency 24 72 8 weeks 3 2 1 3 2 – Follow-up (months) 10 See above 40–50 40 8 20 10 8 30 Total Total sessions (n) 120–150 120–150 See above 300 240 60 1320 25 120 500 Duration (min/week) No contact See above Active Active contact and no contact No contact listWait listWait listWait Active Control condition Three training groups: memory reasoning strategy, and computerized speed processingof See above Auditory information processing (Posit Science, CA, USA) Auditory information processing (Posit Science) Memory strategy (method loci)of Activity planning, self-assertiveness training, relaxation techniques, stress management, use of external memory aids, memory training and motor exercise Memory strategy training (spaced retrieval, memory book, semantic association, logical location) within a larger mixed intervention Memory strategy training Auditory information processing (Posit Science) Cognitive training Sample size (n) 2832 healthy 2832 older adults randomly assigned of 67% original sample 487 healthy older adults healthy 182 older adults 22 healthy older adults and MCI 18 AD patients10 50 MCI patients MCI 20 patients MCI 47 patients ACTIVE: Advanced Cognitive Training for Independent and Vital Elderly; AD: Alzheimer’s disease; ADAS-Cog: Alzheimer’sinhibitors; disease assessment GDS: Geriatric scale-cognitive depression scale; subscale; IADL: Instrumental ADL: Activities activities daily of living; daily of living; ChEI: Cholinesterase MCI: Mild cognitive impairment; MMSE: Mini-mental status exam; NPI: Neuropsychiatry inventory. 3. Case–controlTable studies that assess the effects of cognitive training on cognitive function in older adults. Study Ball al. et (ACTIVE) Willis al. et (ACTIVE) Smith al. et (IMPACT) Mahncke al. et (IMPACT) Engviv al. et Kurz al. et al. et Troyer Belleville al. et Barnes al. et

future science group Aging Health (2010) 6(5) 575 review – Reichman, Fiocco & Rose [81] [85] [83] [82] [80] [86] [84] Ref. Significantfar transfer effects MMSE, behavioral disturbances; depressive symptoms Profileof mood states MMSE, GDS ADAS-Cog MMSE, NPI, GDS, IADL, basic ADL ADL MMSE, basic ADL, depression MMSE, functional activities questionnaire, GDS ADAS-Cog Significant training and near transfer effects Memory, verbal fluency, matrices Raven’s Memory functioning questionnaire, memory controllability questionnaire,episodic recall (words, stories, grocery lists, names and faces) – Prose memory, word repetition test, Corsi blocks, Raven’s matrices, digit cancellation, semantic and phonemic fluency, constructional and ideomotor apraxia andVerbal visuospatial memory, verbal fluency, visuospatial processing speed Face–name association, orientation, object memory, change (for purchase), balancing checkbook, continuous performance test – 3 6 – 9 2 3 12 Follow-up (months) 72 96 520 12 6 24 103 Total Total sessions (n) 12 6 225 180 45 90 60 Duration (min/week) No contact and ChEI alone No contact Active Active Active Active Active Control condition Computerized cognitive training with ChEI Computerized training of attention, reasoning, visuospatial abilities with ChEI Memory strategy training (cueing, categorization, chunking, method loci) of within a larger, multifaceted intervention Multidomain computer training, NPT Memory strategy training Cognitive rehabilitation training Multidomain training (pen and paper) Cognitive training Sample size (n) 86 AD patients 59 MCI MCI 59 patients MCI 19 patients AD patients 11 34 AD patients 44 AD patients MCI 12 AD, 72 patients al. et 3. Case–controlTable studies that assess the effects of cognitive training on cognitive function in older adults. Study Rozzini al. et Rapp al. et Requena Galante al. et Cahn-Weiner al. et Loewenstein al. et Olazaran al. et ACTIVE: Advanced Cognitive Training for Independent and Vital Elderly; AD: Alzheimer’s disease; ADAS-Cog: Alzheimer’sinhibitors; disease assessment GDS: Geriatric scale-cognitive depression scale; subscale; IADL: Instrumental ADL: Activities activities daily of living; daily of living; ChEI: Cholinesterase MCI: Mild cognitive impairment; MMSE: Mini-mental status exam; NPI: Neuropsychiatry inventory.

576 www.futuremedicine.com future science group Exercising the brain to avoid cognitive decline – Review [88] [87] Ref. Significantfar transfer effects MMSE, quality life of assessment and GDS ADAS-Cog, MMSE, rapid disability rating scale-2 and GDS Significant training and near transfer effects Logical memory test, visual reproduction test, digit span test, verbal series attention test and verbal fluencytest fluencyVerbal and story recall – 5.5 Follow-up (months) 5 72 Total Total sessions (n) 60 75 Duration (min/week) Active Active Control condition Memory strategy and attention training Multidomain (attention, gnosis language, memory, orientation, calculation), internet-based program within a multifactorial intervention Cognitive training Sample size (n) 37 AD37 patients 46 AD patients ACTIVE: Advanced Cognitive Training for Independent and Vital Elderly; AD: Alzheimer’s disease; ADAS-Cog: Alzheimer’sinhibitors; disease assessment GDS: Geriatric scale-cognitive depression scale; subscale; IADL: Instrumental ADL: Activities activities daily of living; daily of living; ChEI: Cholinesterase MCI: Mild cognitive impairment; MMSE: Mini-mental status exam; NPI: Neuropsychiatry inventory. 3. Case–controlTable studies that assess the effects of cognitive training on cognitive function in older adults. Study Davis al. et al. et Tarraga

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intervention effect (pre- and post-intervention conclusions with the observation that the number difference) was significant on two of the three of well-controlled studies and numbers of partici- primary outcome memory performance meas- pants was limited at the time of their ana­lysis. ures (delayed list recall and face-name asso- In addition, none of the studies they evaluated ciation). A significant pre-post effect was also employed an individualized cognitive training found on measures of subjective memory and strategy that was specifically geared towards the well-being. There was no improvement in the deficits and needs of each patient. performance of either individuals with MCI or In a more recent review, Sitzer and coworkers normal elderly people who were randomized to also conducted a meta-ana­lysis [43]. They the wait-list condition. The investigators con- searched MEDLINE and PsycINFO databases cluded that the results of this study suggest that to identify peer-reviewed reports of controlled individuals with MCI can improve their per- trials of cognitive training for AD. Based on formance on episodic memory when provided their inclusion criteria, 17 published articles with structured cognitive training. were analyzed using Cohen’s d to establish effect In summary, in all three studies that enlisted sizes. The authors reported that an overall effect individuals with MCI into a cognitive training size of 0.47 was observed for all cognitive train- intervention, participants benefited from the ing strategies across all measured outcomes. treatment in some way, including improvements Mean effect sizes were higher for restorative in near transfer tasks (e.g., recall of lists or face– (0.54) than for compensatory (0.36) strategies. name associations) to domains as far reaching Cognitive domain-specific effect sizes ranged as activities of daily living and subjective meas- from 2.16 (verbal and visual learning) to -0.38 ures of memory, mood and overall well-being. (visuospatial functioning). The investigators Although these studies suggest enhancement concluded that cognitive training does demon- effects, longitudinal studies are required to deter- strate promise in the treatment of AD. Medium mine whether interventions prevent or slow the effect sizes were evident for learning, memory, progression to AD. executive functioning, activities of daily liv- ing, general cognitive problems, depression and Cognitive training interventions self-rated general functioning. However, they in dementia cautioned that most studies report small sample The results of cognitive interventions in dementia sizes and use of neuropsychological test meas- have been mixed. Clare and coworkers conducted ures instead of performance-based measures of a Cochrane Database systematic review on the daily functioning to determine the effectiveness effectiveness and impact of cognitive rehabilita- of the training intervention. Finally, a majority tion and cognitive training focused on improv- of studies employ a combination of treatment ing memory for early-stage AD and vascular strategies that confound the ability to draw dementia [56]. Their review utilized the CDCIG conclusions about the effect of any one specific Specialized Register, containing records from intervention. Therefore, the effectiveness of MEDLINE, EMBASE, CINAHL, PsycINFO cognitive training interventions in AD remains and several other databases. For their ana­lysis, equivocal. Clearly more research is needed. they only included randomized clinical trials comparing cognitive rehabilitation or cognitive Nontraditional cognitive methods training interventions with comparison condi- & alternative approaches tions. Ultimately, six studies met the inclusion A variety of studies have now been published criteria. Data from ordinal scales were treated exploring the cognitive benefits of recreational as continuous and a fixed-effects model was activities, social networks, physical fitness and applied in calculating WMD and 95% CI. The other related and integrated activities. The goal investigators reported that none of the six studies of these investigations is to determine whether demonstrated a statistically significant effect of activities that are part of everyday life may result cognitive training interventions in any domain. in better transfer effects to function than stand- However, there were indications of some mod- alone cognitive exercises (training workshops or est effects in various cognitive domains that did computer based). Many of these investigations not reach statistical significance. The research- explore the benefit of activities that are multidi- ers concluded that their findings did not provide mensional and that require creativity as well as strong support for the use of cognitive training new skill acquisition. Although these studies do interventions for patients with early-stage AD or not match the scientific rigor of clinical trials that vascular dementia. However, they tempered their isolate and train a specific cognitive ability, they

578 www.futuremedicine.com future science group Exercising the brain to avoid cognitive decline – Review

fulfill an important role by potentially revealing significant trend towards improvements in exec- potent factors to be targeted by more controlled utive functions and memory [61]. However, active intervention studies in the future. volunteer participants with impaired baseline executive functions showed the greatest degree Nontraditional training of improvement in executive and memory func- In a study using nontraditional cognitive tioning at follow-up while the similarly impaired approaches, de Medeiros and coworkers studied controls declined in executive functions ability whether participation in an autobiographical (p < 0.05). Carlson and colleagues assessed the writing workshop had positive effects on cogni- benefits of Experience Corps in ‘at risk’ volun- tion [57]. A total of 18 physically and cognitively teers (i.e., African–American women with low healthy seniors were enrolled in 90-min writing level education, low income and low Mini-mental sessions over an 8-week period, and were taught a status exam [MMSE] score at baseline) [62]. Not variety of different writing techniques. The inves- only were cognitive improvements found in tigators reported that participants in the struc- executive inhibitory processes, but intervention- tured workshop demonstrated improvements in specific increases in brain activity were observed processing speed, verbal learning and attention. in the prefrontal and anterior Noice and colleagues studied the effects of the- at 6-month follow-up using functional MRI. atre training on cognitive, emotional and physi- This study suggests that engaging in stimulat- ological functions in a cohort of 124 community- ing activities (via volunteering) may enhance dwelling seniors [58]. Participants were assigned to brain plasticity, and presents the possibility of one of two intervention groups (theatre training mapping brain changes to behavioral outcomes. and visual arts education), consisting of nine ses- Overall, nontraditional cognitive approaches sions over 4 weeks. There was a third, no-inter- provide some promising results; however, more vention control group. The authors reported that vigorous randomized control studies are required theatre training participants showed significant in order to elucidate beneficial components of improvements over controls in memory recall, each activity and to isolate the specific cognitive problem-solving and emotional well-being. These domains that are being altered as a result. effects were not seen in the visual arts educa- tion group, who did not perform as well as the Alternative approaches theatre group in and emotional Epidemiological studies show that physical well-being. After 4 months, the problem solving activity [63,64], nutrition [65] and social engage- effects were stable and memory performance con- ment [66,67] may play a protective role against tinued to improve. These same investigators con- brain aging. Furthermore, these findings coin- ducted a related study in a sample of seniors who cide with the animal literature. For example, were less educated and of a lower socioeconomic monkey [68,69] and rodent [19,70] studies have status, residing in publicly subsidized retirement demonstrated that caloric intake restriction may homes. These participants also demonstrated the prevent age-related decrements in brain structure positive impact of theatre training on cognitive and function. In addition, it has been shown that performance [59]. the exercise component of the rodent enriched In an ongoing pilot program called Experience environment (i.e., the running wheel) produces ® Corps [60], researchers are starting to report on additional neurogenesis effects by enabling the benefits of volunteering on brain health. the maturation of neuroblasts into functional The program provides a model that enhances hippo­campal neurons [71]. These studies sug- physical, social and cognitive activity, which is gest that cognitive function may be enhanced expected to produce enhanced mental flexibility, by alternative strategies that indirectly affect improved working memory skills, cooperative brain function. problem solving and other cognitive and func- Given the important role of exercise on brain tional benefits. The initiative consists of older function [72,73], researchers have started to assess volunteers working within a school for grades the combined effects of physical and cognitive K-3 for a minimum of 15 h per week. The work activity on brain health. In a 6-month, rand- involves special areas of need within the school; omized control trial, Klusmann and colleagues literacy tutoring, behavior management and assessed the effects of mental and physical activ- library use. In an 8-month follow-up study, ity on cognitive performance in older women Carlson and coworkers found that when com- 70–93 years of age [74]. Women were randomly pared with controls, older adults who volunteered assigned to an exercise group, a computer course in Experience Corps displayed a nonstatistically group or a control group. At follow-up, women

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in the computer group and the exercise group sector, insurance companies, schools and related demonstrated improvements in episodic memory educational programs. These products include and maintenance in working memory, compared web-based cognitive exercise programs, DVDs, with controls who showed a decline in cognitive corporate training programs and recreational performance. However, this study did not assess games played online or on hand-held devices. the interaction effect between exercise and mental Very few of these products have been scientifi- activity on cognitive outcomes. In a sample of cally tested and fewer still have reported their 19 middle-aged and older adults with subjective findings in peer-reviewed journals. Yet advertise- mild memory complaints, Small and colleagues ments for various products may make rather bold reported on the combined effects of cognitive and claims, such as ‘improve memory by 10 years’. physical exercise, stress reduction and a healthy When scientific studies do attempt to evaluate diet on cognitive performance and cerebral meta- the effectiveness of cognitive training programs bolic activity as measured by positron emission for improving cognitive function, they may reveal tomography data [75]. They reported improve- nothing more than marketing myths. For exam- ment in verbal fluency with correlated changes ple, Owen and colleagues recently conducted in prefrontal cortical metabolism, perhaps indi- an internet-based study on the benefits of play- cating enhanced cognitive reserve. Finally, the ing video games similar to the Nintendo DS™ investigators concluded that such a lifestyle pro- Brain Age games for producing improved cogni- gram may result in enhanced cognitive efficiency tive function [77]. A total of 11,430 volunteers, of a brain region involved in working memory. including experimental (n = 8692) and control In summary, more research is needed to (n = 2738) participants, aged 18–60 years prac- understand what constitutes the most effective ticed a variety of video games designed to train type of cognitive training, the long-term reten- functions such as reasoning, memory and atten- tion of training effects and whether training can tion over 6 weeks. Although improvements were demonstrate transfer of cognitive gains to daily found in the specific trained cognitive tasks, the function or global cognition. Initially, promising authors reported no evidence for transfer effects associations were found between a reduced level of of training to cognitively related untrained tasks. cognitive decline in late-adulthood and a life-long It is important to mention a number of limita- pursuit of cognitive engagement, which supports tions with the study. The study did not enroll the idea of a brain/cognitive reserve. However, adults over 60 years of age, there were substantial the limited number of well-designed trials that dropout rates (approximately 80%) and partici- fully test the nature of benefits attainable from pants only had to perform at least two 10-min cognitive training interventions prevent one from training sessions over 6 weeks in order to be definitively concluding that it is possible to main- included in the ana­lysis. Therefore, the results tain or improve cognitive function, or prevent of the Owen et al. study should not be taken cognitive decline associated with healthy or patho- as definitive evidence against the possibility that logical aging. Furthermore, additional research cognitive training can provide benefits to cogni- is required to assess other life-style domains tive function in later adulthood. Future research (e.g., exercise and nutrition) and how they may is required to determine the effectiveness of interact with cognitive training strategies on various ‘brain training’ video games. brain function. Nonetheless, it is important to Despite the lack of substantiated claims for note that there is also ‘little evidence to suggest cognitive training benefits, the brain fitness that interventions designed to improve cognitive commercial industry is rapidly growing world- function either worsen it or produce unwanted wide with reported sales of US$100 million in side effects’ [76]. Additional research is also needed 2005 having grown to $265 million in 2008. It to determine the intervention-based neurological is anticipated by leading brain fitness industry changes that may occur: whether these changes analysts that this market could achieve between are short or long-lived and whether they may be $1 billion and $4 billion in revenue by 2015 [56]. observed in both healthy and patient groups. Conclusion & future perspective Rise of the commercial brain It is anticipated that as the population contin- fitness movement ues to age rapidly across the globe, cognitive Despite the need for more research to determine disorders such as AD will pose even greater intervention efficacy, a new market of ‘brain fit- public health challenges. As a result, increasing ness’ products have already been developed for attention is being devoted to methods to help the consumer public, the corporate training prevent age-associated cognitive decline. At the

580 www.futuremedicine.com future science group Exercising the brain to avoid cognitive decline – Review

same time, new scientific insights into how cog- the unfortunate experience with the neutra­ nition changes with normal as well as patho- ceutical industry in which commercial interests logical aging continue to emerge. For example, have touted the cognition sparing benefits of observational evidence suggests that throughout herbal and other supplements and remedies in adult life, there may be opportunities to protect the absence of sound supporting scientific data. and even enhance brain and cognitive function However, with these cautions in mind, the through prudent attention to modifying factors opportunities for offering valid hope to protect such as lifestyle, work and recreational choices, our cognitive functions and strengthen our cog- exercise, diet, health management and even nitive weaknesses as we age remains very promis- by other means such as cognitive training. To ing as the understanding of neuroplasticity, brain date, the available scientific data offer promise, reserve and cognitive reserve continues to evolve. but few definitive conclusions. Clearly, much more research is needed in this area. The com- Financial & competing interests disclosure ing decade will probably see an aggressive and William Reichman is President and CEO of Baycrest, focused international research effort to identify which has a major equity stake in a new brain fitness com- proven means to prevent cognitive decline and pany called Cogniciti, Inc. in which he is also a Director. strengthen cognitive functions in healthy aging Alexandra J Fiocco is supported by a Canadian Institute of adults as well as to treat evident dementia. A Health Research Fellowship. The authors have no other potential risk for the field of cognition and aging relevant affiliations or financial involvement with any is that the growth of the largely unregulated organization or entity with a financial interest in or finan- commercial market for brain fitness products cial conflict with the subject matter or materials discussed targeted to consumers will continue to out-pace in the manuscript apart from those disclosed. the advancement of science that demonstrates No writing assistance was utilized in the production of the benefits of these approaches. This has been this manuscript.

Executive summary Rationale behind brain exercise to avoid cognitive decline • The population is aging across the globe at an unprecedented rate. • The aging process is associated with a decline in certain cognitive functions in healthy elderly as well as an increased prevalence of more significant cognitive decline or dementia due to disorders such as Alzheimer’s disease. • Adults appear to retain the ability to maintain and improve cognitive function through mid and late life through the innate biological process of neuroplasticity. Aging-related cognitive decline • Normal aging is associated with changes in specific cognitive domains. Acquired information (vocabulary, knowledge and facts), often described as ‘crystallized intelligence’ is stable with age and may continue to improve over time. • The more dynamic abilities to problem solve, recall new information, manipulate data, and to do so with speed, sometimes described as ‘fluid intelligence’, may decline in the normal aging process. • A substantial number of older people will suffer pathological changes in cognition such as mild cognitive impairment and overt dementia, of which Alzheimer’s disease and stroke are the most common causes. Cognitive training strategies • A limited number of rigorously designed and well-controlled cognitive training programs have demonstrated benefit in improving domain-specific cognitive functions in healthy elderly and mild cognitive impairment patients. • Whether improvement in test performance as a result of domain-specific training is associated with significant improvement in day-to-day functioning in the activities of daily living remains nonconclusive and additional scientific study is required. Brain fitness market • Despite the need for more rigorous studies to validate the efficacy of structured cognitive training programs, a rapidly growing commercial market of ‘brain fitness’ products targeted to consumers has developed. These involve web-based programs, games, executive training sessions and other modalities. Future perspective • With an aging population across the globe, there will be growing interest in preserving brain and cognitive health through adulthood. • More scientific studies will need to be conducted to examine what cognitively stimulating activities, lifestyle choices, nutritional practices and health factors most positively impact brain health as we age. • Ultimately, we will think of ‘brain fitness’ in a similar fashion to how we now approach cardiovascular fitness. To maintain optimal cognitive function as one ages will likely require a combination of good health practices, a steady routine of cognitive and aerobic exercise, pursuing optimal nutrition and having active engagement in stimulating, novel and rewarding social and recreational activities.

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