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Effectiveness of Brain Gaming in Older Adults With Cognitive Impairments: A Systematic Review and Meta-Analysis

      Abstract

      Objective

      This systematic review and meta-analysis evaluates the evidence from randomized clinical trials (RCTs) that designed brain gaming interventions to improve cognitive functions of older adults with cognitive impairments, including mild cognitive impairments and dementia.

      Design

      Systematic review and meta-analysis.

      Setting and Participants

      N/A.

      Measures

      N/A.

      Methods

      Data sources—relevant randomized control trials (RCTs) were identified by a systematic search of databases including Medline, PubMed, PsycINFO, Embase, CINAHL, Web of Science, and Cochrane. RCTs were selected first based on title and abstract review and then on full-text review by independent reviewers using predefined eligibility criteria. Risk of bias (RoB) was assessed using the Cochrane RoB tool and funnel plots. The primary outcome variable was the composite score of global cognitive function.

      Results

      A total of 909 participants with mild cognitive impairment or dementia from 16 RCTs were included in the systematic review. The study quality was modest, and the RoB assessment showed bias in blinding the participants and personnel. Funnel plots showed no evidence of publication bias. The meta-analysis of 14 RCTs revealed no superior effect of brain gaming compared to other interventions on global cognitive function (pooled standardized mean difference = 0.08, 95% confidence interval −0.24, 0.41, P = .61, I2 = 77%). Likewise, no superior effects were found on the cognitive domains of memory, executive function, visuospatial skills, and language.

      Conclusion and Implications

      The findings of this meta-analysis suggest that brain gaming compared with the control intervention does not show significant improvement in standardized tests of cognitive function. Because of considerable heterogeneity in sample size, gaming platform, cognitive status, study design, assessment tools, and training prescription, we cannot confidently refute the premise that brain gaming is an effective cognitive training approach for older adults with cognitive impairments. Recommendations for future research are included.

      Keywords

      Dementia is one of the leading causes of disability. An estimated 50 million adults live with the disease worldwide.
      World Health Organization
      Dementia fact sheet. 2017.
      With the aging population, the global prevalence of dementia is expected to increase to 82 million by the year 2030.
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      World Alzheimer Report 2015: The Global Impact of Dementia: An Analysis of Prevalence, Incidence, Cost and Trends.
      The socioeconomic burden of dementia on patients, families, and societies is already staggering. Alzheimer's disease (AD), a type of dementia, alone is projected to have cost Medicare and Medicaid $195 billion in 2019.
      Costs of Alzheimer’s to Medicare and Medicaid Alzheimer's impact movement.
      Despite the enormous financial and human cost of dementia, effective pharmacologic treatment options remain unavailable.
      • Briggs R.
      • Kennelly S.P.
      • O’neill D.
      Drug treatments in Alzheimer’s disease.
      Therefore, nonpharmacologic treatment interventions, including computerized cognitive training (CCT), are receiving increasing attention to prevent, delay, or improve cognitive impairments.
      • Basak C.
      • Boot W.R.
      • Voss M.W.
      • et al.
      Can training in a real-time strategy video game attenuate cognitive decline in older adults?.
      ,
      • Kueider A.M.
      • Parisi J.M.
      • Gross A.L.
      • et al.
      Computerized cognitive training with older adults: A systematic review.
      The potential benefits of developing effective CCT programs extend beyond people with dementia to include people with mild cognitive impairment (MCI). MCI is considered an at-risk state between healthy aging and dementia that is associated with subjective memory complaints in the absence of objective impairments in cognitive functions and daily-life activities.
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      Subjective memory complaints, mood and MCI: A follow-up study.
      The optimal point for delivery of CCT of people living with MCI continues to be investigated.
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      Computerized and virtual reality cognitive training for individuals at high risk of cognitive decline: Systematic review of the literature.
      ,
      • Lampit A.
      • Hallock H.
      • Valenzuela M.
      Computerized cognitive training in cognitively healthy older adults: A systematic review and meta-analysis of effect modifiers.
      In particular, brain gaming, a nonimmersive, user-friendly form of CCT, has gained tremendous popularity over the past decade. Although there are subjective components to define brain gaming (ie, features that enhance user engagement and motivation), the ability to adapt games based on level of difficulty and therefore provide a challenging or competitive experience to the user is one of the main criteria for inclusion as a brain gaming paradigm.
      • Lampit A.
      • Hallock H.
      • Valenzuela M.
      Computerized cognitive training in cognitively healthy older adults: A systematic review and meta-analysis of effect modifiers.
      ,
      • Sood P.
      • Kletzel S.L.
      • Krishnan S.
      • et al.
      Nonimmersive brain gaming for older adults with cognitive impairment: A scoping review.
      The cognitive tasks must be engineered to enhance the user's engagement and motivation with the game. This adaptability is a core feature that separates basic CCT programs from brain gaming. Electronic brain gaming software may run on desktop and laptop computers, tablets, or mobile devices (ie, iPad, tablet, phone), and gaming hardware that are accessible and frequently used by older adults.
      • Gell N.M.
      • Rosenberg D.E.
      • Demiris G.
      • et al.
      Patterns of technology use among older adults with and without disabilities.
      ,
      • Rentz D.M.
      • Dekhtyar M.
      • Sherman J.
      • et al.
      The feasibility of at-home iPad cognitive testing for use in clinical trials.
      The ease of access to brain gaming through applications on a smartphone has made this industry a billion-dollar business.
      SharpBrains
      Executive summary: Infographic on the Digital Brain Health Market.
      Studies that investigate the effectiveness of brain gaming in older adults with and without cognitive impairments are vital to confirm or refute the claims that are made by the industry.
      Continuing to understand and advance the utility of effective digital at-home cognitive therapies is also timely given the precautions needed to be taken during COVID-19. Telemedicine and remote rehabilitation are more common during the pandemic—for both patients who have COVID-19 and those who do not.
      • Iannaccone S.
      • Castellazzi P.
      • Tettamanti A.
      • et al.
      Role of rehabilitation department for adult individuals with COVID-19: The experience of the San Raffaele Hospital of Milan.
      The potential benefits of engaging in safe, cognitively challenging, and motivating activities afforded by brain gaming may play a vital role in postcare of patients affected by COVID-19, but also in protecting against accelerated cognitive decline due to detriments on mental health.
      • Vatansever D.
      • Wang S.
      • Sahakian B.J.
      Covid-19 and promising solutions to combat symptoms of stress, anxiety and depression.
      ,
      • Bodner K.A.
      • Goldberg T.E.
      • Devanand D.
      • et al.
      Advancing computerized cognitive training for MCI and Alzheimer’s disease in a pandemic and post-pandemic world.
      Although some systematic reviews and meta-analyses demonstrate beneficial effects of CCT on cognitive functions, psychosocial functioning, daily-life activities, and quality of life,
      • Hill N.T.
      • Mowszowski L.
      • Naismith S.L.
      • et al.
      Computerized cognitive training in older adults with mild cognitive impairment or dementia: A systematic review and meta-analysis.
      no study has evaluated the effectiveness of nonimmersive brain gaming on cognitive functions in older adults with MCI and dementia-related AD. A scoping review conducted by our group found 13 randomized controlled trials (RCTs) investigating brain gaming in older adults with MCI and AD. The included studies demonstrate that nonimmersive electronic brain gaming is a safe, feasible, user-friendly, and potentially effective CCT intervention to maintain or improve cognitive functions among older adults with cognitive impairments.
      • Sood P.
      • Kletzel S.L.
      • Krishnan S.
      • et al.
      Nonimmersive brain gaming for older adults with cognitive impairment: A scoping review.
      Although some differences were found in intervention dose, type of brain gaming, and cognitive outcome measures among the included RCTs, we concluded that the studies were sufficiently homogeneous in research design to evaluate the effectiveness of brain gaming by performing a meta-analysis.
      The primary objective of this systematic review and meta-analysis was to quantify the effects of brain gaming intervention on global cognitive function among older adults with MCI or dementia. Secondary objectives were to (1) assess the effect of brain gaming interventions on the cognitive domains such as memory, executive function, visuospatial skills, and language and (2) determine the effect of brain gaming interventions on secondary outcomes, such as activities of daily living (ADL), instrumental activities of daily living (IADL), depression, and quality of life (QoL). In our subgroup analysis, we hypothesized that brain gaming interventions would show larger effect sizes in adults with MCI as compared to dementia. In addition, we evaluated whether intervention dose and type of setting (home vs controlled settings) would impact the magnitude of the intervention effect.

      Methods

      PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analysis) guidelines were followed for this review.
      • Moher D.
      • Liberati A.
      • Tetzlaff J.
      • et al.
      Preferred reporting Items for systematic reviews and meta-analyses: The PRISMA statement.
      The protocol for this review was registered on PROSPERO (Central registration Depository: CRD42015023918).

       Search Strategy

      The literature search was conducted using Ovid Medline, PubMed, PsycINFO, Embase, CINAHL, Web of Science, and the Cochrane Library to identify RCTs, written in English and published from inception to April 2021. The search strategy was based on four main concepts: (1) cognitive impairment or dementia; (2) outcomes (ie, cognition, ADL, QoL); (3) nonimmersive, electronic brain gaming interventions (eg, computer gaming, video gaming); and (4) study designs (controlled, randomized). Combination of multiple text words and medical subject headings (MeSH) were used to extract literature with the assistance of a medical librarian (search strategy, Supplementary Material 1). Manual search yielded additional articles from the reference list of review articles, authors’ own literature file, and Google Scholar. Authors of the studies that had insufficient information were contacted directly via e-mail. A comprehensive 2-level eligibility process was followed to identify studies for inclusion. Level 1 involved screening titles and abstracts to exclude articles that failed to meet our inclusion criteria and level 2 involved screening full texts of remaining studies. The data were independently extracted by 2 reviewers; that is, the first reviewer extracted the data and the second reviewer reviewed data for any discrepancies. Disagreements were resolved through study team discussion.

       Selection Criteria

      Studies included were only RCTs that examined the effect of cognitive interventions using nonimmersive, electronic brain gaming methods as defined by Sood et al
      • Sood P.
      • Kletzel S.L.
      • Krishnan S.
      • et al.
      Nonimmersive brain gaming for older adults with cognitive impairment: A scoping review.
      on cognition among older adults with MCI or dementia.
      Brain gaming technology involves a wide range of computer technologies (hardware and software) such as desktop and laptop computers, mobile computers (ie, iPad, tablet, phone), and video game technologies.
      • Rentz D.M.
      • Dekhtyar M.
      • Sherman J.
      • et al.
      The feasibility of at-home iPad cognitive testing for use in clinical trials.
      ,
      • Gigler K.L.
      • Blomeke K.
      • Shatil E.
      • et al.
      Preliminary evidence for the feasibility of at-home online cognitive training with older adults.
      We chose to investigate brain gaming technology as it is relatively easy to access by older adults at home, clinic, or in the research laboratory.
      • Rentz D.M.
      • Dekhtyar M.
      • Sherman J.
      • et al.
      The feasibility of at-home iPad cognitive testing for use in clinical trials.
      Cognitive impairment status, that is, diagnosis of MCI or dementia, was determined by neuropsychological instruments used to define cognitive status (ie, Mini-Mental State Examination or Montreal Cognitive Assessment) or as reported by the authors (based on the criteria or cognitive evaluation) in the original study. Our primary focus was on cognition and domain-specific cognitive functions such as memory, executive functions, visuospatial functions, and language.
      Studies were excluded if they were case reports, protocols, commentaries, dissertations, book chapters, letters, or conference abstracts. Decision was made to exclude brain gaming interventions that involved immersive or semi-immersive virtual reality games as these games required specialized equipment that are harder to access than nonimmersive brain games. Additionally, any non–computer-based games such as paper-and-pencil games or board games were excluded.

       Risk of Bias and Quality Assessment

      Two reviewers (S.L.K. and P.H.) independently completed risk of bias assessment using a standardized form and Cochrane Risk of Bias tool.
      • Higgins J.P.
      • Altman D.G.
      • Gøtzsche P.C.
      • et al.
      The Cochrane Collaboration’s tool for assessing risk of bias in randomised trials.
      A score of low risk, high risk, or unclear (ie, lack of information or uncertainty over the potential bias) was assigned to each risk of bias criterion.
      • Akl E.A.
      • Sun X.
      • Busse J.W.
      • et al.
      Specific instructions for estimating unclearly reported blinding status in randomized trials were reliable and valid.
      Disagreements were discussed among the reviewers and the research team until an agreement was reached. When the number of studies was at least 10, a comparison-adjusted funnel plot was drawn to assess for publication bias and small study effects. Quality assessment was performed using level-of-evidence hierarchy used in evidence-based clinical medicine as developed by the Center for Evidence-Based Medicine.
      • Phillips B.
      • Ball C.
      • Sackett D.
      • et al.
      Oxford Centre for Evidence-Based Medicine—levels of evidence (March 2009).

       Type of Outcomes

       Primary outcome

      Global cognitive function was considered our primary outcome variable and was obtained from either composite scores or scores on the Mini-Mental State Examination. The composite score was calculated as the grand average mean and standard deviation (SD), derived from the postintervention mean of each cognitive domain measure.

       Secondary outcomes

      Our secondary outcomes included domain-specific cognitive functions such as memory, executive functions, visuospatial functions, and language, reported in at least 2 studies. Other secondary outcomes were ADL, IADL, and QoL.

       Statistical Analysis

      The outcomes in the included studies reported continuous data (mean and SD) and used different outcome measures. Therefore, standardized mean differences (SMDs) with 95% confidence intervals (CIs) were used to estimate the treatment effect to facilitate comparisons across all outcomes. SMDs were pooled and the inverse-variance random effects model was used considering the variability in methodology, participants, and intervention characteristics across studies. SMD between 0.20 and 0.49 represented a small effect, SMD between 0.50 and 0.79 a moderate effect, and SMD of 0.80 and higher a large effect.
      • Higgins J.
      Cochrane Handbook for Systematic Reviews of Interventions. Version 5.1.0.
      Review Manager, version 5 was used for data analysis.
      The Z test was used to determine the treatment effect with a statistical significance threshold of P < .05. Heterogeneity was assessed using the chi-square statistic (2-tailed P < .10) using the Higgins I2 criteria in accordance with the Cochrane Collaboration thresholds, where 25%, 50%, and 75% imply small, moderate, and large heterogeneity, respectively.
      • Higgins J.P.
      • Thompson S.G.
      • Deeks J.J.
      • Altman D.G.
      Measuring inconsistency in meta-analyses.
      Subgroup analysis was conducted to compare the treatment effects in studies with different diagnoses (MCI vs dementia), intervention dosage (intense vs mild, where intense is categorized as more than 3 formal sessions per week whereas less intense interventions is categorized as up to 3 formal sessions per week),
      • Bahar-Fuchs A.
      • Martyr A.
      • Goh A.M.
      • et al.
      Cognitive training for people with mild to moderate dementia.
      and intervention setting (home vs laboratory or clinic).

      Results

       Included Studies

      Figure 1 depicts the PRISMA flowchart of the systematic review and meta-analysis. After duplicate studies were removed, a total of 1291 original studies were initially screened for eligibility. Following title and abstract screening, 207 were full-text articles were independently reviewed by 2 authors. Sixteen studies were included in the systematic review. Two studies were excluded from the meta-analysis. Authors of these 2 studies were contacted but we could not retrieve the necessary data required to conduct the analysis.
      • Barnes D.E.
      • Yaffe K.
      • Belfor N.
      • et al.
      Computer-based cognitive training for mild cognitive impairment: Results from a pilot randomized, controlled trial.
      ,
      • Gooding A.L.
      • Choi J.
      • Fiszdon J.M.
      • et al.
      Comparing three methods of computerised cognitive training for older adults with subclinical cognitive decline.
      Figure thumbnail gr1
      Fig. 1PRISMA flow diagram describing identification and selection of studies for the review.

       Characteristics of Included Studies

      The 16 studies included in this systematic review encompassed 909 participants with mean age ranging from 67 to 82 years. Of those, 461 (51%) participants were males as detailed in Table 1. Twelve studies (75%) included participants with MCI, whereas 3 studies (19%) included participants with dementia. Only 1 study focused on both MCI and dementia.
      Table 1Study Sample Characteristics Table According to Cognitive Status
      Author (Year)Sample size, nAge, y, Mean (SD)Gender, Male/Female, nMMSE Score, Mean
      MCI
       Barnes (2009)
      • Barnes D.E.
      • Yaffe K.
      • Belfor N.
      • et al.
      Computer-based cognitive training for mild cognitive impairment: Results from a pilot randomized, controlled trial.
      Total = 47 (Exp. = 22; Control = 25)Exp. = 74.1 (8.7); Control = 74.8 (7.2)28/19N/R
       Basak (2008)
      • Basak C.
      • Boot W.R.
      • Voss M.W.
      • et al.
      Can training in a real-time strategy video game attenuate cognitive decline in older adults?.
      Total = 39 (Exp. = 19; control = 20)Exp. = 70.05 (4.94); control = 69.10 (6.06)10/29Exp. = 55.68; control = 55.65
      Modified MMSE scores.
       Finn (2011)
      • Finn M.
      • McDonald S.
      Computerised cognitive training for older persons with mild cognitive impairment: A pilot study using a randomised controlled trial design.
      Total = 25 (Exp. = 8; control = 8)Exp. = 69 (7.69); control = 76.38 (6.47)9/16Both groups = 27.76
       Gooding (2015)
      • Gooding A.L.
      • Choi J.
      • Fiszdon J.M.
      • et al.
      Comparing three methods of computerised cognitive training for older adults with subclinical cognitive decline.
      Total = 74 (Exp. = 31; control = 43)Both groups = 75.59 (8.75)43/31Both groups = 50.58 (2.72)
      Modified MMSE scores.
       Hagovská (2016)
      • Hagovská M.
      • Olekszyová Z.
      Impact of the combination of cognitive and balance training on gait, fear and risk of falling and quality of life in seniors with mild cognitive impairment.
      Total = 60 (Exp. = 30; control = 30)Exp. = 67.8 (6.5); control = 68.2 (4.2)29/31Exp. = 25.6 (2.41); control = 24.9 (2.52)
       Hyer (2016)
      • Hyer L.
      • Scott C.
      • Atkinson M.M.
      • et al.
      Cognitive training program to improve working memory in older adults with MCI.
      Total = 68 (Exp. = 34; control = 34)Exp. = 75.1 (7.4); control = 75.2 (7.8)32/36Both groups = 26
       Lin (2016)
      • Lin F.
      • Heffner K.L.
      • Ren P.
      • et al.
      Cognitive and neural effects of vision-based speed-of-processing training in older adults with amnestic mild cognitive impairment: A pilot study.
      Total = 21 (Exp. = 10; control = 11)Exp. = 72.9 (8.2); control = 73.1 (9.6)11/10N/R
       Miller (2013)
      • Miller K.J.
      • Dye R.V.
      • Kim J.
      • et al.
      Effect of a computerized brain exercise program on cognitive performance in older adults.
      Total = 74 (Exp. = 38; control = 36)Exp. = 82.2 (4.4); control = 81.5 (7.6)24/50Exp = 28 (1.5); control = 27.9 (1.7)
       Park (2018)
      • Park J.H.
      • Park J.H.
      Does cognition-specific computer training have better clinical outcomes than non-specific computer training? A single-blind, randomized controlled trial.
      Total = 78 (Exp. = 39; Control = 39)Exp. = 67.64 (4.55); control = 66.95 (4.10)42/36Exp. = 26.67 (1.68); control = 26.41 (1.94)
       Savulich (2017)
      • Savulich G.
      • Piercy T.
      • Fox C.
      • et al.
      Cognitive training using a novel memory game on an iPad in patients with amnestic mild cognitive impairment (aMCI).
      Total = 42 (Exp. = 21; control = 21)Exp. = 75.2 (7.4); Control = 76.9 (8.3)25/17Exp. = 26.6 (2.9); Control = 26.8 (2.2)
       Styliadis
      Styliadis (2015) had 2 control groups.
      (2015)
      • Styliadis C.
      • Kartsidis P.
      • Paraskevopoulos E.
      • et al.
      Neuroplastic effects of combined computerized physical and cognitive training in elderly individuals at risk for dementia: An eLORETA controlled study on resting states.
      Total = 42 (Exp. = 14; control = 28)Exp. = 72.71 (6.57); AC = 71.07 (4.38); PC = 67.64 (3.97)15/27Exp. = 25.14 (3.22); AC = 26.21 (1.97); PC = 25 (1.77)
       Valdes (2012)
      • Valdes G.E.
      • O’Connor L.M.
      • Edwards D.J.
      The effects of cognitive speed of processing training among older adults with psychometrically-defined mild cognitive impairment.
      Total = 195 (Exp. = 85; control = 110)Exp. = 76.95 (6.53); control = 78.34 (6.3)129/66N/R
      Dementia
       Cavallo (2016)
      • Cavallo M.
      • Hunter E.M.
      • van der Hiele K.
      • et al.
      Computerized structured cognitive training in patients affected by early-stage Alzheimer’s disease is feasible and effective: A randomized controlled study.
      Total = 80 (Exp. = 40; control = 40)Exp. = 76.5 (2.88); control = 76.33 (3.82)29/51Exp. = 22.65 (1.74); control = 23.05 (2.44)
       Lee (2013)
      • Lee G.Y.
      • Yip C.C.
      • Yu E.C.
      • et al.
      Evaluation of a computer-assisted errorless learning-based memory training program for patients with early Alzheimer’s disease in Hong Kong: A pilot study.
      Total = 13 (Exp. = 7; control = 6)N/R6/13Exp. = 17 (3.5); control = 17.6 (4.7)
       Man (2011)
      • Man D.W.
      • Chung J.C.
      • Lee G.Y.
      Evaluation of a virtual reality-based memory training programme for Hong Kong Chinese older adults with questionable dementia: A pilot study.
      Total = 34 (Exp. = 20; control = 14)Exp. = 80.3 (1.21); control = 80.22 (1.31)5/12Exp. = 21 (3.79); control = 23 (3.96)
      Both
       Galante (2007)
      • Galante E.
      • Venturini G.
      • Fiaccadori C.
      Computer-based cognitive intervention for dementia: Preliminary results of a randomized clinical trial.
      Total = 11 (Exp. = 7; control = 4)Both groups = 76 (6)N/RExp. = 22.9 (3.1); control = 23.1 (1.8)
      AC, active control; Exp., experimental; MCI, mild cognitive impairment; MMSE, Mini-Mental State Examination; N/R, not reported; PC, passive control.
      Modified MMSE scores.
      Styliadis (2015) had 2 control groups.
      The type of control group varied across studies, with sample sizes ranging from 11 to 195 participants. Eleven studies used an active comparison group such as other nongaming computer-based activities,
      • Barnes D.E.
      • Yaffe K.
      • Belfor N.
      • et al.
      Computer-based cognitive training for mild cognitive impairment: Results from a pilot randomized, controlled trial.
      • Gooding A.L.
      • Choi J.
      • Fiszdon J.M.
      • et al.
      Comparing three methods of computerised cognitive training for older adults with subclinical cognitive decline.
      • Cavallo M.
      • Hunter E.M.
      • van der Hiele K.
      • et al.
      Computerized structured cognitive training in patients affected by early-stage Alzheimer’s disease is feasible and effective: A randomized controlled study.
      • Valdes G.E.
      • O’Connor L.M.
      • Edwards D.J.
      The effects of cognitive speed of processing training among older adults with psychometrically-defined mild cognitive impairment.
      • Galante E.
      • Venturini G.
      • Fiaccadori C.
      Computer-based cognitive intervention for dementia: Preliminary results of a randomized clinical trial.
      • Hagovská M.
      • Olekszyová Z.
      Impact of the combination of cognitive and balance training on gait, fear and risk of falling and quality of life in seniors with mild cognitive impairment.
      • Hyer L.
      • Scott C.
      • Atkinson M.M.
      • et al.
      Cognitive training program to improve working memory in older adults with MCI.
      • Lee G.Y.
      • Yip C.C.
      • Yu E.C.
      • et al.
      Evaluation of a computer-assisted errorless learning-based memory training program for patients with early Alzheimer’s disease in Hong Kong: A pilot study.
      • Lin F.
      • Heffner K.L.
      • Ren P.
      • et al.
      Cognitive and neural effects of vision-based speed-of-processing training in older adults with amnestic mild cognitive impairment: A pilot study.
      • Man D.W.
      • Chung J.C.
      • Lee G.Y.
      Evaluation of a virtual reality-based memory training programme for Hong Kong Chinese older adults with questionable dementia: A pilot study.
      • Styliadis C.
      • Kartsidis P.
      • Paraskevopoulos E.
      • et al.
      Neuroplastic effects of combined computerized physical and cognitive training in elderly individuals at risk for dementia: An eLORETA controlled study on resting states.
      whereas 5 studies used a passive control group.
      • Basak C.
      • Boot W.R.
      • Voss M.W.
      • et al.
      Can training in a real-time strategy video game attenuate cognitive decline in older adults?.
      ,
      • Man D.W.
      • Chung J.C.
      • Lee G.Y.
      Evaluation of a virtual reality-based memory training programme for Hong Kong Chinese older adults with questionable dementia: A pilot study.
      ,
      • Finn M.
      • McDonald S.
      Computerised cognitive training for older persons with mild cognitive impairment: A pilot study using a randomised controlled trial design.
      • Miller K.J.
      • Dye R.V.
      • Kim J.
      • et al.
      Effect of a computerized brain exercise program on cognitive performance in older adults.
      • Savulich G.
      • Piercy T.
      • Fox C.
      • et al.
      Cognitive training using a novel memory game on an iPad in patients with amnestic mild cognitive impairment (aMCI).
      One study used both active and passive control groups,
      • Styliadis C.
      • Kartsidis P.
      • Paraskevopoulos E.
      • et al.
      Neuroplastic effects of combined computerized physical and cognitive training in elderly individuals at risk for dementia: An eLORETA controlled study on resting states.
      and another study used a therapist-led training program as control intervention.
      • Man D.W.
      • Chung J.C.
      • Lee G.Y.
      Evaluation of a virtual reality-based memory training programme for Hong Kong Chinese older adults with questionable dementia: A pilot study.
      Seven of 16 studies were conducted in the United States, 2 each were conducted in Italy and China, and 1 each in Australia, Eastern Slovakia, Greece, Republic of Korea, and United Kingdom (Supplementary Table 1). Although the type of brain gaming varied considerably across studies, most studies (n = 14, 88%) used a computer platform. Intervention periods ranged between 4 and 16 weeks. The training frequency varied between 2 and 15 sessions per week and the duration per session varied between 20 and 100 minutes.

       Risk Bias Assessment and Quality of Studies

      Based on OCEBM level of evidence, all RCTs were rated as level 1B, except 1 study that was 1C.
      • Styliadis C.
      • Kartsidis P.
      • Paraskevopoulos E.
      • et al.
      Neuroplastic effects of combined computerized physical and cognitive training in elderly individuals at risk for dementia: An eLORETA controlled study on resting states.
      Five studies categorized themselves as pilot studies.
      • Barnes D.E.
      • Yaffe K.
      • Belfor N.
      • et al.
      Computer-based cognitive training for mild cognitive impairment: Results from a pilot randomized, controlled trial.
      ,
      • Lee G.Y.
      • Yip C.C.
      • Yu E.C.
      • et al.
      Evaluation of a computer-assisted errorless learning-based memory training program for patients with early Alzheimer’s disease in Hong Kong: A pilot study.
      • Lin F.
      • Heffner K.L.
      • Ren P.
      • et al.
      Cognitive and neural effects of vision-based speed-of-processing training in older adults with amnestic mild cognitive impairment: A pilot study.
      • Man D.W.
      • Chung J.C.
      • Lee G.Y.
      Evaluation of a virtual reality-based memory training programme for Hong Kong Chinese older adults with questionable dementia: A pilot study.
      ,
      • Finn M.
      • McDonald S.
      Computerised cognitive training for older persons with mild cognitive impairment: A pilot study using a randomised controlled trial design.
      Eight of the 16 studies specified their randomization method. Some studies used a computer-generated randomization method,
      • Valdes G.E.
      • O’Connor L.M.
      • Edwards D.J.
      The effects of cognitive speed of processing training among older adults with psychometrically-defined mild cognitive impairment.
      ,
      • Hagovská M.
      • Olekszyová Z.
      Impact of the combination of cognitive and balance training on gait, fear and risk of falling and quality of life in seniors with mild cognitive impairment.
      ,
      • Park J.H.
      • Park J.H.
      Does cognition-specific computer training have better clinical outcomes than non-specific computer training? A single-blind, randomized controlled trial.
      pseudo-randomization method,
      • Cavallo M.
      • Hunter E.M.
      • van der Hiele K.
      • et al.
      Computerized structured cognitive training in patients affected by early-stage Alzheimer’s disease is feasible and effective: A randomized controlled study.
      or site-specific block method,
      • Barnes D.E.
      • Yaffe K.
      • Belfor N.
      • et al.
      Computer-based cognitive training for mild cognitive impairment: Results from a pilot randomized, controlled trial.
      whereas others allocated participants into groups based on order of recruitment
      • Galante E.
      • Venturini G.
      • Fiaccadori C.
      Computer-based cognitive intervention for dementia: Preliminary results of a randomized clinical trial.
      or by drawing lots or slips of paper.
      • Man D.W.
      • Chung J.C.
      • Lee G.Y.
      Evaluation of a virtual reality-based memory training programme for Hong Kong Chinese older adults with questionable dementia: A pilot study.
      ,
      • Finn M.
      • McDonald S.
      Computerised cognitive training for older persons with mild cognitive impairment: A pilot study using a randomised controlled trial design.
      Overall, the quality of the studies was modest (Figure 2). The results of risk of bias assessment revealed that description of blinding of the participant and personnel was mostly unclear or low. In addition, the blinding of outcome assessment (detection bias) was largely unclear or low. Attrition bias was low. The funnel plot suggested no evidence of publication bias for overall cognitive functions from the composite scores (Supplementary Figure 1).

       Primary Outcome

       Global cognitive function from composite scores

      Fourteen studies were included for calculation of global cognition function (Figure 3). The overall effect size was small (SMD –0.08, 95% CI –0.24, 0.41) and nonsignificant (P = .61). The heterogeneity across the studies was high (I2 = 77%).
      Figure thumbnail gr3
      Fig. 3Effect of brain gaming on overall cognitive functions in mild cognitive impairment and dementia.

       Global cognitive function from Mini-Mental State Examination

      Six studies used Mini-Mental State Examination as outcome tool to determine global cognition (Supplementary Figure 2). The meta-analysis of global cognition revealed a small (SMD –0.07, 95% CI –0.46, 0.59), nonsignificant effect size (P = .49) and moderate heterogeneity across the studies (I2 = 70%).

       Secondary Outcomes: Cognitive Domains

       Memory

      Seven studies reported memory outcomes and were pooled to determine the effect of brain gaming on memory (Supplementary Figure 3). The overall effect size was small (SMD –0.17, CI –0.40, 0.06) and nonsignificant (P = .16). There was small heterogeneity across the studies (I2 = 21%).

       Executive Function

      As illustrated in Supplementary Figure 4, the pooled data for 8 studies demonstrated no superior effect of brain gaming on executive function (SMD –0.03, CI –0.30, 0.24; P = .82). The heterogeneity was small across the studies (I2 = 34%).

       Visuospatial Function

      Data from 3 studies were pooled to determine the effect of brain gaming on visuospatial functions (Supplementary Figure 5). The overall effect size was small (SMD –0.09, CI –0.37, 0.18) and nonsignificant (P = .51). Heterogeneity across the studies was small (I2 = 0%).

       Language

      Supplementary Figure 6 shows the pooled data from 3 studies, demonstrating a large effect (SMD 1.28, CI –0.23, 2.78) that was nonsignificant (P = .10) in favor of the brain gaming intervention on language. However, there was considerable heterogeneity across the studies (I2 = 96%).

       Secondary Outcomes: Other

       ADL

      As shown in Supplementary Figure 7, the pooled data from 2 studies demonstrating a small (SMD 0.04, CI –0.78, 0.86), nonsignificant (P = .93) effect size on ADL, with no heterogeneity across studies (I2 = 0%).

       IADL

      Supplementary Figure 8 pools the data from 6 studies, showing a small (SMD 0.14, CI –0.13, 0.42) and nonsignificant (P = .31) effect size in IADL. There was no heterogeneity across the studies (I2 = 0%).

       Depression

      Supplementary Figure 9 shows a small (SMD –0.09, CI –0.56, 0.39) and nonsignificant (P = .72) effect size on depression based on data from 3 studies. There was small heterogeneity across the studies (I2 = 13%).

       Quality of life

      Data from 2 studies were pooled to demonstrate large heterogeneity across the studies (I2 = 98%) on QoL. The overall effect size was small but nonsignificant (P = .75), equally favoring the brain gaming and the control interventions (Supplementary Figure 10).

       Subgroup Analysis on Effects of Brain Gaming

       MCI vs dementia

      Figure 4 displays the results of brain gaming on overall cognitive function in MCI and dementia, separately. Subgroup analysis based on diagnosis suggest that participants with dementia did not benefit more than participants with MCI from brain gaming on overall cognitive functions (SMD –0.19, CI –0.54, 0.16, vs SMD 0.16, CI –0.23, 0.54, respectively). Studies that focused on MCI demonstrated higher heterogeneity (I2 = 82%) vs studies that focused on dementia (I2 = 0%).
      Figure thumbnail gr4
      Fig. 4Effect of brain gaming on overall cognitive functions in mild cognitive impairment and dementia subgroup analysis based on the intervention.

       Weekly intervention dosage (sessions per week)

      Studies were categorized based on dosage sessions per week similar to the one used by Bahar-Fuchs et al,
      • Bahar-Fuchs A.
      • Martyr A.
      • Goh A.M.
      • et al.
      Cognitive training for people with mild to moderate dementia.
      as more intense (ie, more than 3 formal sessions per week) vs less intense interventions (ie, up to 3 formal sessions per week). We found no significant differences between intervention dosage of brain gaming (SMD 0.00, CI –0.30, 0.30, vs SMD –0.18, CI –0.37, 0.74, P = .57) on overall cognitive function (Supplementary Figure 11).

       Intervention Setting

      Subgroup analysis revealed that categorized by setting did not change the benefit of brain gaming (Supplementary Figure 12). Studies focused on clinical and laboratory settings demonstrated higher heterogeneity (I2 = 87%) vs studies focused on home (I2 = 42%) and others (I2 = 1%).

      Discussion

      The aim of our systematic review and meta-analysis was to evaluate the effectiveness of brain gaming—a subdomain of computerized cognitive training (CCT)—for adults with cognitive impairments. The evidence base for brain gaming in older adults with cognitive impairments has grown rapidly, partly driven by unsubstantiated claims from commercial application developers that brain gaming can maintain or improve cognitive functions. Based on our systematic review of 16 studies and our meta-analysis of 14 studies, we conclude that brain gaming is not more effective than control interventions in improving cognitive functions among adults with MCI or dementia. However, because of considerable heterogeneity of the included studies in terms of study design (eg, training prescription, gaming platform, and setting), we cannot confidently refute the premise that brain gaming is an effective cognitive training approach in this population.
      Our conclusions largely resonate with a recent review on the effectiveness of 12 or more weeks of CCT (including immersive and nonimmersive brain gaming) on maintaining or improving cognitive function in MCI.
      • Gates N.J.
      • Rutjes A.W.
      • Di Nisio M.
      • et al.
      Computerised cognitive training for 12 or more weeks for maintaining cognitive function in cognitively healthy people in late life.
      CCT interventions did not prove to be more efficacious than other interventions on speed of processing, verbal fluency, and quality of life. The low quality of evidence of the included studies hampered the authors’ ability to make firm conclusions about the effectiveness of CCT in MCI.
      • Gates N.J.
      • Rutjes A.W.
      • Di Nisio M.
      • et al.
      Computerised cognitive training for 12 or more weeks for maintaining cognitive function in cognitively healthy people in late life.
      Conversely, 2 meta-analyses recently reported positive effects of CCT in older adults with cognitive impairments. Hu and colleagues found that CCT significantly improves cognitive functions especially related to various constructs of memory in participants with subjective cognitive decline and MCI.
      • Hu M.
      • Wu X.
      • Shu X.
      • et al.
      Effects of computerised cognitive training on cognitive impairment: A meta-analysis.
      Zhang and colleagues reported positive effect sizes in favor of CCT for global cognitive function, memory and working memory in adults with MCI.
      • Zhang H.
      • Huntley J.
      • Bhome R.
      • et al.
      Effect of computerised cognitive training on cognitive outcomes in mild cognitive impairment: A systematic review and meta-analysis.
      Previous systematic reviews that compared the effectiveness of CCT also found significant, yet modest, improvements on cognitive functions in older adults with cognitive impairments.
      • Coyle H.
      • Traynor V.
      • Solowij N.
      Computerized and virtual reality cognitive training for individuals at high risk of cognitive decline: Systematic review of the literature.
      ,
      • Hill N.T.
      • Mowszowski L.
      • Naismith S.L.
      • et al.
      Computerized cognitive training in older adults with mild cognitive impairment or dementia: A systematic review and meta-analysis.
      ,
      • Ge S.
      • Zhu Z.
      • Wu B.
      • et al.
      Technology-based cognitive training and rehabilitation interventions for individuals with mild cognitive impairment: A systematic review.
      Methodologic differences between the included RCTs, such as inconsistencies in study design, training prescription (duration and intensity), type of training program, outcome measures, and severity of cognitive dysfunction, may have led to the ambiguity of conclusions among the systematic reviews and meta-analyses. In particular, the scope of studies included in our systematic review and meta-analysis may be an explanation for the discrepancy between our findings and those of others.
      • Coyle H.
      • Traynor V.
      • Solowij N.
      Computerized and virtual reality cognitive training for individuals at high risk of cognitive decline: Systematic review of the literature.
      ,
      • Hill N.T.
      • Mowszowski L.
      • Naismith S.L.
      • et al.
      Computerized cognitive training in older adults with mild cognitive impairment or dementia: A systematic review and meta-analysis.
      ,
      • Ge S.
      • Zhu Z.
      • Wu B.
      • et al.
      Technology-based cognitive training and rehabilitation interventions for individuals with mild cognitive impairment: A systematic review.
      Previous reviews did not particularly focus on the brain gaming literature, rather including several CCT paradigms, such as immersive virtual reality technology or CCT without adaptability in difficulty of training. Perhaps the ease of use, adaptability, and engaging elements that typically define brain gaming come at the expense of effectiveness of targeted, immersive CCT interventions or nonadaptive training.
      • Flak M.M.
      • Hol H.R.
      • Hernes S.S.
      • et al.
      Adaptive computerized working memory training in patients with mild cognitive impairment. A randomized double-blind active controlled trial.
      Previous systematic reviews also reported a differential effect of CCT on disease severity, with adults with MCI benefiting more from CCT compared to those with dementia.
      • Hill N.T.
      • Mowszowski L.
      • Naismith S.L.
      • et al.
      Computerized cognitive training in older adults with mild cognitive impairment or dementia: A systematic review and meta-analysis.
      ,
      • Bahar-Fuchs A.
      • Martyr A.
      • Goh A.M.
      • et al.
      Cognitive training for people with mild to moderate dementia.
      ,
      • Huntley J.
      • Gould R.
      • Liu K.
      • et al.
      Do cognitive interventions improve general cognition in dementia? A meta-analysis and meta-regression.
      Hu and colleagues reported CCT to be most beneficial when initiated early in the course of cognitive decline.
      • Hu M.
      • Wu X.
      • Shu X.
      • et al.
      Effects of computerised cognitive training on cognitive impairment: A meta-analysis.
      Participants with subjective cognitive complaints showed twice as much benefit from CCT compared to participants with MCI. Based on our analyses, we found no difference in effectiveness of brain gaming interventions across these subgroups.
      There is no consensus among reviews whether benefits of CCT generalize to ADLs or QoL measures. Coyle et al
      • Coyle H.
      • Traynor V.
      • Solowij N.
      Computerized and virtual reality cognitive training for individuals at high risk of cognitive decline: Systematic review of the literature.
      reported significant improvements in depression, but no improvements in ADL and QoL. Hill et al,
      • Hill N.T.
      • Mowszowski L.
      • Naismith S.L.
      • et al.
      Computerized cognitive training in older adults with mild cognitive impairment or dementia: A systematic review and meta-analysis.
      on the other hand, reported most improvements on several psychosocial functions, including depression, QoL, and neuropsychiatric functions, among individuals with MCI. Our review did not reveal any benefits of brain gaming on ADL and QoL outcomes; this was expected because we included studies that only assessed brain gaming as the intervention. As highlighted by Harvey and colleagues, CCT by itself is not the typical strategy aimed at improving functional outcomes in clinical populations.
      • Harvey P.D.
      • McGurk S.R.
      • Mahncke H.
      • et al.
      Controversies in computerized cognitive training.
      Strengths of our review include a wide search of the available literature on brain gaming interventions. There was considerable heterogeneity across studies in study design; thus, we advocate that our findings should be interpreted with caution. Although our review included only RCT designs, many of the included RCTs had small sample size, had short-term interventions, and were pilot studies. Larger RCTs, with consistent outcome reporting, would improve the ability to generate grounded conclusions regarding the effects of brain gaming. For example, for domain analysis, each domain was measured by a variety of outcome measures, which created heterogeneity in the meta-analyses. Another limitation to our work is that we assessed interventions that incorporated only brain gaming in the experimental group. Several studies, not included in our analysis, assessed multimodal cognitive training, which includes, for example, brain gaming combined with a pharmacologic intervention,
      • Rozzini L.
      • Costardi D.
      • Chilovi B.V.
      • et al.
      Efficacy of cognitive rehabilitation in patients with mild cognitive impairment treated with cholinesterase inhibitors.
      • Tárraga L.
      • Boada M.
      • Modinos G.
      • et al.
      A randomised pilot study to assess the efficacy of an interactive, multimedia tool of cognitive stimulation in Alzheimer’s disease.
      • Lenze E.J.
      • Stevens A.
      • Waring J.D.
      • et al.
      Augmenting computerized cognitive training with vortioxetine for age-related cognitive decline: A randomized controlled trial.
      and other nonpharmacologic interventions, such as physical exercise,
      • Hagovská M.
      • Olekszyová Z.
      Impact of the combination of cognitive and balance training on gait, fear and risk of falling and quality of life in seniors with mild cognitive impairment.
      ,
      • Bamidis P.D.
      • Fissler P.
      • Papageorgiou S.G.
      • et al.
      Gains in cognition through combined cognitive and physical training: The role of training dosage and severity of neurocognitive disorder.
      ,
      • Wiloth S.
      • Werner C.
      • Lemke N.C.
      • et al.
      Motor-cognitive effects of a computerized game-based training method in people with dementia: A randomized controlled trial.
      reminisce therapy,
      • Barban F.
      • Annicchiarico R.
      • Pantelopoulos S.
      • et al.
      Protecting cognition from aging and Alzheimer’s disease: A computerized cognitive training combined with reminiscence therapy.
      ,
      • Barban F.
      • Mancini M.
      • Cercignani M.
      • et al.
      A pilot study on brain plasticity of functional connectivity modulated by cognitive training in mild Alzheimer’s disease and mild cognitive impairment.
      occupational therapy,
      • Chandler M.J.
      • Locke D.E.
      • Duncan N.L.
      • et al.
      Computer versus compensatory calendar training in individuals with mild cognitive impairment: Functional impact in a pilot study.
      ,
      • Talassi E.
      • Guerreschi M.
      • Feriani M.
      • et al.
      Effectiveness of a cognitive rehabilitation program in mild dementia (MD) and mild cognitive impairment (MCI): A case control study.
      pencil-and-paper exercises,
      • Eckroth-Bucher M.
      • Siberski J.
      Preserving cognition through an integrated cognitive stimulation and training program.
      ,
      • Gaitán A.
      • Garolera M.
      • Cerulla N.
      • et al.
      Efficacy of an adjunctive computer-based cognitive training program in amnestic mild cognitive impairment and Alzheimer’s disease: A single-blind, randomized clinical trial.
      general education,
      • Chandler M.J.
      • Locke D.E.
      • Duncan N.L.
      • et al.
      Computer versus compensatory calendar training in individuals with mild cognitive impairment: Functional impact in a pilot study.
      or video gaming.
      • Hughes T.F.
      • Flatt J.D.
      • Fu B.
      • et al.
      Interactive video gaming compared to health education in older adults with MCI: A feasibility study.
      Ge et al
      • Ge S.
      • Zhu Z.
      • Wu B.
      • et al.
      Technology-based cognitive training and rehabilitation interventions for individuals with mild cognitive impairment: A systematic review.
      reviewed many of these multimodal games and concluded that more studies are needed to understand the advantages of a multimodal cognitive intervention approach for older adults with MCI.

      Conclusions and Implications

      The currently available data on brain gaming, designed to improve cognitive function in older adults with MCI and dementia, suggests that this approach does not improve cognitive function compared with the control group. Although individual studies continue to suggest a promising effect, collectively, the data do not bear this out. The considerable heterogeneity among the studies in terms of overall study design reflects a need for the research community to focus on salient design features and outcomes measurements so that the field can move forward in determining the best CCT to improve cognitive functions of older individuals with cognitive impairments.

      Acknowledgment

      We would like to acknowledge the role of the American Congress of Rehabilitation Medicine ACRM and contribution of members of the Measurement Networking Group and Applied Cognition Geriatric Team—Lilian Hoffecker, Carrie Ciro, Michael Cary, Michelle Thai, and David Berbrayer—for their contribution during early stages of data collection and analysis.

      Supplementary Material 1

      Search terms used across databases.

      Concept of Dementia

      Mild cognitive impairment, MCI, cognitive disorder, memory loss, memory deterioration, dementia, Alzheimer's, age-associated memory impairment, AAIM, cognition disorder.

      Concept of Cognitive Outcomes

      Cognitive performance, cognitive outcomes, cognitive function, cognitive measures, cognitive assessments, cognitive improvements, cognitive evaluation, mindfulness, attention attentiveness, memory, comprehension, awareness, brain function, neurological outcomes, neurological functions, neuropsychological, Activities of Daily Living, ADL, Instrumental Activities of Daily Living, IADL, eating, bathing, dressing, toileting, transferring, continence, incontinence, driving, finances, shopping, meal preparation, housework, telephone use, medication management, psychological tests, psychometrics.

      Concept of Brain Gaming

      Gaming, video games, internet games, online games, computer games, brain games, online games, interactive mental games, mobile phone games, electronic or computer or online puzzles, electronic or computer or online word games, electronic or computer or online brain exercises, Lumosity, Tetris, Fitbrain, Brain-Age, Nintendo, Wii, Braintraining101, Scientificbraintraining, Yale Perception, Brain Metrix, Cognifit, Happy Neuron, Brainturk, Sharp Brains, Braintrain, Braingymmer, Fitbrains, BrainHQ, Posit Science, Dakim.

      Concept of Controlled Studies

      Controlled, control group, randomized, blinded, placebo, clinical trial, multicenter, comparative study, evaluation study, prospective study.

      Appendix

      Supplementary Table 1Study Intervention Characteristics
      Author (Year)CountryIntervention PlatformLocation and SettingTechnology UsedDosage
      Sessions/WeekSession Time (min)No. of weeks
      MCI
       Barnes (2009)
      • Barnes D.E.
      • Yaffe K.
      • Belfor N.
      • et al.
      Computer-based cognitive training for mild cognitive impairment: Results from a pilot randomized, controlled trial.
      USAComputer- and software-based gameHomePosit Science Corporation (San Francisco, CA)51006
       Basak (2008)
      • Basak C.
      • Boot W.R.
      • Voss M.W.
      • et al.
      Can training in a real-time strategy video game attenuate cognitive decline in older adults?.
      USAComputer-based gameLaboratoryComputer Program (eMAC 17)15904-5
       Finn (2011)
      • Finn M.
      • McDonald S.
      Computerised cognitive training for older persons with mild cognitive impairment: A pilot study using a randomised controlled trial design.
      AustraliaUnclearUnclearLuminosity30 sessions over an average of 11.43 wk
       Gooding (2015)
      • Gooding A.L.
      • Choi J.
      • Fiszdon J.M.
      • et al.
      Comparing three methods of computerised cognitive training for older adults with subclinical cognitive decline.
      USAComputer-based gameEither at hospital or remotely from homePosit Science's BrainFitness21616
       Hagovská (2016)
      • Hagovská M.
      • Olekszyová Z.
      Impact of the combination of cognitive and balance training on gait, fear and risk of falling and quality of life in seniors with mild cognitive impairment.
      Eastern SlovakiaComputer-based gameOutpatient psychiatric clinicCogniPlus23010
       Hyer (2016)
      • Hyer L.
      • Scott C.
      • Atkinson M.M.
      • et al.
      Cognitive training program to improve working memory in older adults with MCI.
      USAComputer-based gameClinic or homeCogmed5405-7
       Lin (2016)
      • Lin F.
      • Heffner K.L.
      • Ren P.
      • et al.
      Cognitive and neural effects of vision-based speed-of-processing training in older adults with amnestic mild cognitive impairment: A pilot study.
      USAComputer-based gameHomeINSIGHT online program (Posit Science, San Francisco, CA)4606
       Miller (2013)
      • Miller K.J.
      • Dye R.V.
      • Kim J.
      • et al.
      Effect of a computerized brain exercise program on cognitive performance in older adults.
      USAComputer- and software-based gameHomeDakim's Brain Fitness520-258
       Park (2018)
      • Park J.H.
      • Park J.H.
      Does cognition-specific computer training have better clinical outcomes than non-specific computer training? A single-blind, randomized controlled trial.
      Republic of KoreaComputer-based gameClinicThe CoTras Program33010
       Savulich (2017)
      • Savulich G.
      • Piercy T.
      • Fox C.
      • et al.
      Cognitive training using a novel memory game on an iPad in patients with amnestic mild cognitive impairment (aMCI).
      United KingdomiPad-based gameHomeCustom Computer program (eMAC 17 in monitor with Mac- and PC-based software)8604
       Styliadis (2015)
      • Styliadis C.
      • Kartsidis P.
      • Paraskevopoulos E.
      • et al.
      Neuroplastic effects of combined computerized physical and cognitive training in elderly individuals at risk for dementia: An eLORETA controlled study on resting states.
      GreeceComputer-based gameClinic, under supervisionGreek adaptation of the Brain Fitness software (Posit Science Corporation, San Francisco, CA, USA)3-5608
       Valdes (2012)
      • Valdes G.E.
      • O’Connor L.M.
      • Edwards D.J.
      The effects of cognitive speed of processing training among older adults with psychometrically-defined mild cognitive impairment.
      USAComputer-based gameClinicN/R2605
      Dementia
       Cavallo (2016)
      • Cavallo M.
      • Hunter E.M.
      • van der Hiele K.
      • et al.
      Computerized structured cognitive training in patients affected by early-stage Alzheimer’s disease is feasible and effective: A randomized controlled study.
      ItalyComputer-based gameNot reportedRehabilitative software Brainer1 (https://www.brainer.it/)33012
       Lee (2013)
      • Lee G.Y.
      • Yip C.C.
      • Yu E.C.
      • et al.
      Evaluation of a computer-assisted errorless learning-based memory training program for patients with early Alzheimer’s disease in Hong Kong: A pilot study.
      Hong Kong, ChinaTouchscreen computer-based gameNot reportededucamigos.com2306
       Man (2011)
      • Man D.W.
      • Chung J.C.
      • Lee G.Y.
      Evaluation of a virtual reality-based memory training programme for Hong Kong Chinese older adults with questionable dementia: A pilot study.
      Hong Kong, ChinaComputer-based gameClinicNonimmersive virtual reality3-4304-5
      Both
       Galante (2007)
      • Galante E.
      • Venturini G.
      • Fiaccadori C.
      Computer-based cognitive intervention for dementia: Preliminary results of a randomized clinical trial.
      ItalyComputer-based gameNot reportedTraining NeuroPsicologico3604
      MCI, mild cognitive impairment, N/R, not reported.
      Figure thumbnail fx1
      Supplementary Fig. 1Funnel plot of the 14 included studies on main outcome measure of overall cognitive function. SMD, standard mean difference, SE, standard error.
      Figure thumbnail fx2
      Supplementary Fig. 2Effect of brain gaming on overall cognitive measured by Mini-Mental State Examination (MMSE) in mild cognitive impairment and dementia.
      Figure thumbnail fx3
      Supplementary Fig. 3Effect of brain gaming on memory in mild cognitive impairment and dementia.
      Figure thumbnail fx4
      Supplementary Fig. 4Effect of brain gaming on executive function in mild cognitive impairment and dementia.
      Figure thumbnail fx5
      Supplementary Fig. 5Effect of brain gaming on visuospatial function in mild cognitive impairment and dementia.
      Figure thumbnail fx6
      Supplementary Fig. 6Effect of brain gaming on language in mild cognitive impairment and dementia.
      Figure thumbnail fx7
      Supplementary Fig. 7Effect of brain gaming on activities of daily living (ADL) in mild cognitive impairment and dementia.
      Figure thumbnail fx8
      Supplementary Fig. 8Effect of brain gaming on instrumental activities of daily living (IADL) in mild cognitive impairment and dementia.
      Figure thumbnail fx9
      Supplementary Fig. 9Effect of brain gaming on depression in mild cognitive impairment and dementia.
      Figure thumbnail fx10
      Supplementary Fig. 10Effect of brain gaming on quality of life in mild cognitive impairment and dementia.
      Figure thumbnail fx11
      Supplementary Fig. 11Effect of brain gaming on overall cognitive functions in mild cognitive impairment and dementia subgroup analysis based on weekly intervention dosage (sessions per week).
      Figure thumbnail fx12
      Supplementary Fig. 12Effect of brain gaming on overall cognitive functions in mild cognitive impairment and dementia subgroup analysis based on the intervention setting.

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