IntroductionBackground

Life expectancy has increased worldwide as people have better access to health care services and an improved standard of living. As a result, people are living longer [-]. According to the United Nations World Population Aging 2020 report [], the number of people aged ≥65 years has increased up to 727 million worldwide. The older population group is expected to increase to 16% by 2050 compared with 9.3% in 2020 []. The older population group is more likely to develop cognitive impairment [,], which is a decline in cognitive abilities and functions such as memory, attention, concentration, learning, and language [,]. According to the Alzheimer’s Association, approximately 12% to 18% of people aged ≥60 years have mild cognitive impairment (MCI) [].

MCI refers to a decline in the ability to learn new information or recall stored information and occurs along a continuum that ranges from normal to severely impaired cognition []. Although inconsistencies exist in screening for MCIs, it is certain that they occur because of brain changes owing to multiple factors, including older age, injuries to the brain, diabetes, hypertension, stroke, depression, and physical inactivity []. Memory is one of the main cognitive functions that decline with age. Memory is known as the ability of the brain to hold information and recall it as needed. There are different types of memory: verbal, nonverbal, and working memory. Verbal memory refers to a person’s ability to remember what they read or hear of information that was already learned []. On the other hand, nonverbal memory refers to storing, retrieving, and remembering nonverbal information, content, or experiences, such as images, feelings, tastes, sounds, shapes, and smells []. Furthermore, memory is divided into 3 types according to the period for which the memorized information is retained: short-term, long-term, and working memory. Short-term memory temporarily holds a limited amount of information [], whereas long-term memory refers to the relatively permanent storage and recall of information []. Working memory refers to the temporary storage of a limited amount of information to be used in the execution of cognitive activities such as learning, reasoning, and comprehension [].

Several nonpharmacological interventions can be used to improve memory, such as physical exercise, cognitive behavioral therapy, psychosocial therapy, good nutrition, and serious games []. Serious games are defined as electronic games that are played for purposes beyond leisure to promote the users’ mental, physical, and social well-being [,]. Recent evidence suggests that exergames are effective in improving physical and cognitive function in people with MCIs [] as well as their compliance and adherence to medical interventions embedded in serious games [,]. Previous systematic reviews have shown that serious games have the potential to prevent or alleviate mental disorders such as depression [], anxiety [], and cognitive impairment []. Several types of serious games have been used to improve cognitive abilities, namely (1) cognitive training games (which deliver cognitive activities to maintain or improve cognitive functions) and (2) exergames (which entail physical exercises as part of the intended gameplay []). Compared with conventional exercise and cognitive training, serious games can positively affect mood, social functioning, mental health well-being, and cognitive flexibility in older adults [-].

Research Problem and Objectives

The effectiveness of serious games in improving memory has been assessed by many studies. To draw definitive conclusions about the effectiveness of serious games, the findings of these studies need to be pooled and aggregated. Several systematic reviews have summarized the evidence from these studies; however, they had a different aim and scope from this review. Specifically, these reviews (1) focused on healthy older adults and not necessarily those with cognitive impairment [,-] (therefore, future reviews should consider older adults with cognitive impairment), (2) included pilot randomized controlled trials (RCTs) and quasi-experiments [,,,] (thus, future reviews should include only RCTs), (3) performed an outdated search (>5 years [,,]; therefore, an updated review or a new review are required), (4) did not assess the quality of evidence [,,,,] (thus, the quality of the evidence should be assessed in future reviews), (5) only focused on a specific type of serious game such as cognitive training games [,] and exergames [,,] (hence, future reviews should consider all types of serious games), (6) focused on a certain type of memory (working memory []; therefore, all types of memory should be considered in upcoming reviews), or (7) did not compare the effect of serious games with a specific comparator (eg, no intervention, conventional exercises, or conventional cognitive activities [,,,,]; thus, further reviews are needed to compare the effect of serious games with a specific comparator). To address the aforementioned gaps, this study aimed to assess the effectiveness of serious games in improving memory among older adults with cognitive impairment. This review focused only on memory as other cognitive domains—for example, global cognition [], executive functions [], and processing speed []—were targeted by previous reviews.

Methods

The authors followed the expanded version of the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines to conduct a systematic review and meta-analyses (). The protocol for this review was registered with PROSPERO (CRD42021292150).

Eligibility Criteria

This review included only RCTs that looked at the effectiveness of serious games in improving memory in older adults with cognitive impairment. The target intervention in this review was serious games supplied on any digital platform, such as computers (PCs), consoles (Xbox and PlayStation), mobile phones, handheld devices, Nintendo, or any other computerized device. Furthermore, components of gaming had to be used as an important and major technique for reaching the intervention’s goal. Serious games had to be used solely for the purpose of therapy. Studies combining serious games with other interventions were eligible if the control group received the same adjacent intervention. Nondigital games and those used for other purposes, such as monitoring, screening, diagnosis, and research, were excluded.

The study focused on the older adult population (aged ≥60 years) who had any type of cognitive impairment or condition (eg, MCI, Alzheimer disease, or dementia). Their diagnosis had to be confirmed by checking the inclusion criteria or baseline scores against standardized diagnostic criteria (eg, Mini-Mental State Examination and Montreal Cognitive Assessment). This review did not focus on healthy older adults, health care providers, or caregivers. No restrictions were applied regarding sex and ethnicity.

The main outcome of interest in this review was memory regardless of the type (verbal, nonverbal, or working memory) and regardless of the tool used for measuring the outcome. Studies were excluded if they assessed only other cognitive outcomes (eg, language and processing speed), cost-effectiveness, acceptance, feasibility, or satisfaction. This review focused on outcome data that were measured immediately after the intervention rather than on follow-up data.

Only RCTs conducted in English and from 2010 onward were considered. Pilot or feasibility RCTs, quasi-experiments, observational studies, and reviews were omitted. Studies published as journal articles, conference proceedings, or dissertations were included. Reviews, conference abstracts, proposals, editorials, and commentaries were all excluded. Finally, no restrictions related to the country of publication, comparator, or study setting were applied.

Information Sources and Search Strategy

The studies that were relevant to this review were found by searching 7 bibliographic databases: MEDLINE (via Ovid), PsycINFO (via Ovid), EMBASE (via Ovid), CINAHL (via EBSCO), IEEE Xplore, ACM Digital Library, and Scopus. Furthermore, we searched the search engine Google Scholar. Owing to the high number of papers obtained through Google Scholar, only the first 10 pages (ie, 100 records) were taken into account as they were automatically ordered based on their relevance []. The first author (AA) conducted the search on August 6, 2021. An automatic alert was set up to retrieve studies that were added to the databases after that date; this continued for 16 weeks (ending on December 5, 2021). Forward reference list checking (ie, screening studies that cited the included studies) and backward reference list checking (ie, screening the reference lists of the included studies and relevant reviews) were carried out to retrieve further studies.

To develop the search query for this review, the authors consulted 2 experts in digital mental health and checked the search queries used in other systematic reviews within this field. The chosen search terms were related to the target population (eg, cognitive impairment), target intervention (eg, serious games and exergames), and target study design (eg, RCTs). summarizes the search query that was used for searching each of the 8 databases.

Selection Process

Relevant studies were identified taking the following steps. First, the obtained studies were imported into EndNote X8 (Clarivate Analytics) to identify and delete duplicate items. Second, the titles and abstracts of all the retrieved studies were evaluated in the second phase by 2 reviewers (AA and MH) working independently. Finally, the 2 reviewers independently evaluated the entire texts of the studies included in the previous step. Any disagreements in the 2 previous steps were resolved via discussion. The interrater agreement (Cohen κ) in steps 2 and 3 was 0.94 and 0.96, respectively, indicating a near-perfect level of interrater agreement [].

Data Collection Process

In total, 2 independent reviewers (AA and MH) used Microsoft Excel to extract data from all the included studies. The data extraction form used to extract data from the included studies was pilot-tested using 2 of the included studies (). The reviewers’ disagreements were resolved through discussion. An interrater agreement of 0.85 was observed, indicating a near-perfect degree of agreement. If data such as the mean, SD, and sample size were unavailable from the published studies, contact was made with the first and corresponding authors in an attempt to retrieve them.

Study Risk of Bias Assessment

The Cochrane Collaboration recommends assessing the risk of bias via 2 independent reviewers (AA and MH) using the Risk of Bias 2 (RoB 2) tool []; as such, these guidelines were followed for this review. The RoB 2 tool assesses the risk of bias in 5 domains of RCTs: randomization process, deviations from intended interventions, missing outcome data, measurement of the outcome, and selection of the reported result []. The risk of bias judgments in these domains were used to determine the overall risk of bias of each included study. Any inconsistencies in decisions between the reviewers were resolved by consulting a third reviewer. Interrater agreement between the reviewers was near perfect (Cohen κ=0.93) [].

Synthesis Methods

A narrative and statistical approach was used to synthesize the information acquired. In our narrative synthesis, we used texts and tables to describe the characteristics of the included studies (demographic, intervention, comparator, and outcome variables). The results of the experiments were categorized and pooled based on measured outcome (ie, verbal, nonverbal, and working memory) and the comparator (ie, control, conventional exercises, conventional cognitive training, and other serious games). A meta-analysis was conducted when at least two studies with the same measured outcome and comparator submitted enough data (ie, mean, SD, and number of participants in each intervention group). Owing to the type of data for the outcome of interest (memory) being continuous and the methods used to measure the outcome being variable throughout the included studies, the standardized mean difference (SMD; Cohen d) was used to analyze the overall effect of each study. The random effects model was used for the analysis because of the high clinical heterogeneity among the meta-analyzed studies in terms of serious game characteristics (eg, type, duration, frequency, and period), population characteristics (eg, sample size, mean age, and health condition), and outcome measures (ie, tools and follow-up period). As several studies used more than one outcome measure to assess memory, the dependency on effect sizes within or across studies will be introduced in the meta-analysis. As a result, a multilevel meta-analysis considering the dependency on effect sizes and sampling covariance between the effect sizes was used [-]. Namely, the multilevel meta-analysis should be applied when effect sizes within the same study are very likely to be more similar to each other than the effect sizes across studies []. The R (version 4.3.1; R Foundation for Statistical Computing) statistical package was used to perform the analysis. We used the function rma.mv in the library metafor, which is a library in R, to perform the multilevel meta-analysis [].

If we observed a statistically significant difference between the groups in a meta-analysis, we further sought to examine if it was clinically significant. The phrase “minimal clinically important difference” (MCID) refers to the smallest change in a measured outcome that a patient would consider worthwhile and significant enough to warrant a change in treatment. The MCID boundaries were calculated as 0.5 times the SMD of the meta-analyzed studies.

We calculated I2 and a chi-square P value to investigate the degree and statistical significance of the heterogeneity in the meta-analyzed studies, respectively. A chi-square P value of ≤.05 suggests heterogeneous meta-analyzed studies []. When I2 ranged from 0% to 40%, 30% to 60%, 50% to 90%, and 75% to 100%, the degree of heterogeneity was judged to be insignificant, moderate, substantial, or considerable, respectively [].

Certainty of Evidence

To appraise the overall quality of evidence resulting from the meta-analyses, we applied the Grading of Recommendations Assessment, Development, and Evaluation approach [], which assesses the quality of evidence based on 5 domains: risk of bias, inconsistency (ie, heterogeneity), indirectness, imprecision, and publication bias []. In total, 2 reviewers independently rated the overall quality of the meta-analyzed evidence, and disagreements were resolved through discussion. The interrater agreement of the reviewers was considered near perfect (Cohen κ=0.87) [].

ResultsStudy Selection

The total number of records retrieved by searching the predefined databases was 618 (). Of these 618 records, 161 (26.1%) duplicates were removed using the EndNote software. Checking titles and abstracts of the remaining records led to the exclusion of 52.3% (323/618). After reading the full texts of the remaining 134 publications, 116 (86.6%) were excluded, mainly because of the population (n=67, 57.8%). The list of studies that were excluded after screening the full texts is provided in . No additional studies were found through backward and forward reference list checking. In total, 18 RCTs were included in this review [-]. Of these 18 studies, 15 (83%) were included in 10 meta-analyses [-,,,-]. A total of 17% (3/18) of the studies were excluded from the meta-analyses because 33% (1/3) [] did not report the data required for the meta-analysis (eg, mean and SD) and 67% (2/3) [,] compared serious games with other serious games that had different characteristics; therefore, including them in a meta-analysis would not make sense.

‎Figure 1. Flowchart of the study selection process. View this figureStudy Characteristics

The included studies were published between 2012 and 2021 (). The year in which the largest number of included studies was published was 2015 (4/18, 22%). The included studies were carried out in 13 different countries, and there was a general equal distribution of studies in these countries. All the included studies were peer-reviewed journal articles except for a book chapter included (1/18, 6%). The trial type was parallel RCT in most of the included studies (17/18, 94%).

The sample size of the included studies varied from 20 to 209, with an average of 81. The mean age of the participants in the included studies ranged from 66 to 83.1 years, with an average of 74.5 years. The percentage of men in the included studies ranged from 21.5% to 71%, with an average of 46.5%. The participants in most of the included studies had MCI (14/18, 78%). Participants were recruited from clinical settings in 67% (12/18) of the studies, from the community in 28% (5/18) of the studies, and from both clinical settings and the community in 6% (1/18) of the studies.

Serious games alone were used as interventions in 89% (16/18) of the included studies, whereas the remaining 11% (2/18) of the studies used serious games combined with conventional exercises [] or sham exercises [] (). The included studies used 16 different serious games. On the basis of the therapeutic modality that they delivered, the serious games used in the included studies were grouped into 2 types: cognitive training games (16/18, 89%) and exergames (2/18, 11%). Games were designed with a “serious” purpose from the beginning (designed serious games) in all studies except for 6% (1/18) that used a purpose-shifted game (which was not designed as a serious game from the start but rather was used for a serious purpose). The most common platform used for playing the games were computers (14/18, 78%). In 67% (12/18) of the studies, serious games were played under the supervision of health care providers or caregivers. The duration of the games in the included studies ranged from 7 to 90 minutes, and the most common duration was 60 minutes (7/18, 39%). The frequency of playing the games varied between 2 and 7 times per week, but it was 2 times per week in half of the studies (9/18, 50%). The period of intervention ranged from 2 to 25 weeks, but it was ≤12 weeks in 72% (13/18) of the studies.

The comparison groups received only passive interventions in 39% (7/18) of the studies, whereas they received only active interventions in 44% (8/18) of the studies (eg, conventional exercises and conventional cognitive activities; ). In total, 17% (3/18) of the studies delivered both active and passive interventions as comparators. The duration of the active comparators ranged from 7 to 100 minutes. The frequency of the active comparators varied between 2 and 7 times per week. The period of the active comparators varied between 2 and 25 weeks. Most of the included studies (16/18, 89%) measured more than one outcome. The measured outcomes were verbal memory in 78% (14/18) of the studies, nonverbal memory in 61% (11/18) of the studies, and working memory in 67% (12/18) of the studies. The studies used 32 different tools to measure these outcomes, but the most common tool used was the Wechsler Memory Scale Third Edition (7/18, 39%). The outcomes were measured immediately after the intervention in all the included studies (18/18, 100%). The follow-up period ranged from 4 to 264 weeks. Participant attrition was reported in 89% (16/18) of the studies, and it ranged from 0 to 23.

Table 1. Characteristics of the studies and populations (N=18).StudyYearCountryPublication typeRCTa typeSample sizeAge, meanSex (male; %)Health conditionSettingValdes et al []2012United StatesJournal articleParallel19577.733.3MCIbClinicalZhuang et al []2013ChinaJournal articleParallel3383.124.2MCI; dementiaClinicalHagovská et al []2016SlovakiaJournal articleParallel806751.2MCIClinicalSingh et al []2014AustraliaJournal articleFactorial10070.132MCICommunityGooding et al []2016United StatesJournal articleParallel9675.658.1MCIClinicalLiao et al []2021TaiwanJournal articleParallel6181.532.6MCICommunityFinn and McDonald []2015AustraliaJournal articleParallel3175.671MCIClinicalPark and Park []2017South KoreaJournal articleParallel7867.353.8MCICommunityCavallo et al []2016ItalyJournal articleParallel8076.436.3ADcClinicalLeung et al []2015Hong KongJournal articleParallel20970.121.5MCICommunityYang and Kwak []2017South KoreaJournal articleParallel207170ADClinicalTarnanas et al []2014GreeceBook chapterParallel11470.339MCIClinicalFlak et al []2019NorwayJournal articleParallel856666.7MCIClinicalHerrera et al []2012FranceJournal articleParallel2276.650MCIClinicalSavulich et al []2017United KingdomJournal articleParallel4276.159.5MCIClinicalBoller et al []2012FranceJournal articleParallel3681.236.1ADClinicalKarssemeijer et al []2019NetherlandsJournal articleParallel11579.953.9DementiaClinical, communityHyer et al []2015United StatesJournal articleParallel6875.247.1MCICommunity

aRCT: randomized controlled trial.

bMCI: mild cognitive impairment.

cAD: Alzheimer disease.

Table 2. Characteristics of the interventions (N=18).StudySerious game nameSerious game typePlatformSupervisionDuration (minutes)Frequency (times per week)Period (weeks)Valdes et al []SOPTCognitive training gamePCSupervised6025Zhuang et al []NRaCognitive training gamePCSupervised75324Hagovská et al []CogniPlusCognitive training gamePCSupervised and unsupervised30210Singh et al []COGPACKCognitive training gamePCSupervised75225Gooding et al []BrainFitnessCognitive training gamePCSupervised and unsupervised60217Liao et al []Tano and LongGoodExergameKinect, VRb headsetSupervised60312Finn and McDonald []E-PrimeCognitive training gamePCSupervisedNR24Park and Park []CoTrasCognitive training gamePCSupervised30310Cavallo et al []BrainerCognitive training gamePCSupervised30312Leung et al []BrainFitnessCognitive training gamePCUnsupervised60313Yang and Kwak []Brain-CareCognitive training gamePCUnsupervised60212Tarnanas et al []Virtual Reality MuseumCognitive training gameVR headsetSupervised90221Flak et al []CogmedCognitive training gamePCUnsupervised30-4055Herrera et al []NRCognitive training gamePCSupervised60212Savulich et al []Game ShowCognitive training gameTabletSupervised6024Boller et al []NRCognitive training gamePCSupervised7-1032Karssemeijer et al []NRExergameStationary bicycle and screenSupervised30-50312Hyer et al []CogmedCognitive training gamePCSupervised and unsupervised4075-7

aNR: not reported.

bVR: virtual reality.

Table 3. Characteristics of the comparators and outcomes (N=18).StudyComparatorDuration (minutes)Frequency (times per week)Period (weeks)Measured outcomesOutcome measuresFollow-upAttrition, NValdes et al []ControlN/AaN/AN/AVMbHVLTc; RAVLTd; RBMTeAfter the intervention; 52-, 104-, 156-, and 261-week follow-upNRfZhuang et al []ControlN/AN/AN/AVMACE-RgAfter the intervention10Hagovská et al []Conventional exercises30710VMACE-RAfter the intervention2Singh et al []Conventional exercises+sham cognitive training; serious games+conventional exercises; controlConventional exercises+sham cognitive training: 75; serious games+conventional exercises: 100; control: 60225VM; NVMhBVRT-Ri; WMS-III-LMjAfter the intervention; 74-week follow-up14Gooding et al []Empirically validated serious game; commercially available serious game60217VM; NVMWMS-R-VR-IIk; WMS-R-LMl; BSRTmAfter the intervention22Liao et al []Conventional exercises60312VM; WMnCVLTo; SBTTpAfter the intervention15Finn and McDonald []ControlNR24VM; WMWMS-IV-VPA-IIq; WMS-IV-SSrAfter the intervention7Park and Park []Commercially available exergame30310VM; WMRAVLT; WAIS-DSBsAfter the intervention0Cavallo et al []ControlN/AN/AN/AVM; NVM; WMRBMT; WMS-R-DSBt; TSWRTuAfter the intervention; 24-week follow-up4Leung et al []Control60313VM; NVM; WMWMS-III-FPv; WMS-III-LM; WMS-III-DSTw; WMS-III-VSSTxAfter the intervention0Yang and Kwak []ControlN/AN/AN/AVM; NVM; WMROCFTy; SVLTz; WMS-III-DSBaaAfter the intervention0Tarnanas et al []Control; conventional cognitive activities90221VM; NVM; WMROCFT; RAVLT; WMS-III-DSBAfter the intervention9Flak et al []Nonadaptive serious game30 to 4055VM; NVM; WMROCFT; WMS-III-FIIab; WMS-III-LM; CVLT-IIac; WMS-III-DSB; WMS-III-SSad; WMS-III-LNSaeAfter the intervention; 4- and 16-week follow-up17Herrera et al []Conventional cognitive activities60212VM; NVM; WMROCFT-Raf; BEM-WLTRag; MMSE-Rah; WMS-R-DSBAfter the intervention; 24-week follow-upNRSavulich et al []ControlN/AN/AN/ANVMBVRT-RAfter the intervention0Boller et al []Serious game; control7 to 1032NVM; WMSRTai; n-BTaj; RSTakAfter the intervention0Karssemeijer et al []Conventional exercises (aerobic exercises); conventional exercises (relaxation and flexibility exercises)30 to 50312NVM; WMLLT-Ral; WAIS-III-DSam; WMS-III-VSSTAfter the intervention; 24-week follow-up23Hyer et al []Nonadaptive serious game4075 to 7WMWMS-III-DST; WMS-III-LNSAfter the intervention; 12-week follow-up9

aN/A: not applicable.

bVM: verbal memory.

cHVLT: Hopkins Verbal Learning Test.

dRAVLT: Rey Auditory Verbal Learning Test.

eRBMT: Rivermead Behavioral Memory Test.

fNR: not reported.

gACE-R: Addenbrooke Cognitive Examination-Revised.

hNVM: nonverbal memory.

iBVRT-R: Benton Visual Retention Test-Revised, Fifth Edition.

jWMS-III-LM: Wechsler Memory Scale Third Edition-Logical Memory.

kWMS-R-VR-II: Wechsler Memory Scale-Revised-Visual Reproductions II.

lWMS-R-LM: Wechsler Memory Scale-Revised-Logical Memory.

mBSRT: Buschke Selective Reminding Test.

nWM: working memory.

oCVLT: California Verbal Learning Test.

pSBTT: spatial n-back task test.

qWMS-IV-VPA-II: Wechsler Memory Scale Fourth Edition-Verbal Paired Associates II.

rWMS-IV-SS: Wechsler Memory Scale Fourth Edition-Symbol Span.

sWAIS-DSB: Wechsler Adult Intelligence Scale-Digit Span Backwards.

tWMS-R-DSB: Wechsler Memory Scale-Revised-Digit Span Backwards.

uTSWRT: two-syllable word repetition test.

vWMS-III-FP: Wechsler Memory Scale Third Edition-Family Pictures.

wWMS-III-DST: Wechsler Memory Scale Third Edition-Digit Span Test.

xWMS-III-VSST: Wechsler Memory Scale Third Edition-Visual-Spatial Span Test.

yROCFT: Rey-Osterrieth complex figure test.

zSVLT: Seoul Verbal Learning Test.

aaWMS-III-DSB: Wechsler Memory Scale Third Edition-Digit Span Backwards Test.

abWMS-III-FII: Wechsler Memory Scale Third Edition-Faces II.

acCVLT-II: California Verbal Learning Test-Second Edition.

adWMS-III-SS: Wechsler Memory Scale Third Edition-Symbol Span.

aeWMS-III-LNS: Wechsler Memory Scale Third Edition-Letter-Number Sequencing.

afROCFT-R: Rey-Osterrieth complex figure test-Revised.

agBEM-WLTR: Batterie d’Efficience Mnesique-word list total recall.

ahMMSE-R: Mini-Mental State Examination-Recall.

aiSRT: source recognition task.

ajn-BT: n-back task.

akRST: reading span task.

alLLT-R: Location Learning Test-Revised.

amWAIS-III-DS: Wechsler Adult Intelligence Scale Second Edition-Digit Span.

Risk of Bias in the Studies

An appropriate random allocation sequence for the randomization process was used in 44% (8/18) of the studies. Researchers in 39% (7/18) of the studies concealed the allocation sequence until participants were assigned to the interventions. The groups were comparable at baseline in all studies (18/18, 100%). Thus, the risk of bias owing to the randomization process was rated as low in only 33% (6/18) of the studies ().

Participants and those who delivered the interventions were aware of the assigned interventions during the trial in 67% (12/18) and 83% (15/18) of the studies, respectively. None of the studies reported a deviation from the intended intervention because of experimental contexts; however, 11% (2/18) of the studies provided insufficient information to verify if protocol deviations had occurred. Appropriate analysis methods (eg, intention-to-treat analysis) were used in 89% (16/18) of the studies to estimate the effect of the intervention. According to these judgments, the risk of bias because of deviations from the intended interventions was low in 78% (14/18) of the studies ().

Missing outcome data were <5% in 44% (8/18) of the studies. There was evidence that the findings were not biased by missing outcome data in only 6% (1/18) of the studies. The missing outcome data resulted from reasons that were documented and not related to the outcome in 28% (5/18) of the studies. Therefore, there was a low risk of bias because of missing outcome data in 78% (14/18) of the studies ().

In all the included studies (18/18, 100%), the outcomes of interest were evaluated using appropriate measures, and the measurement methods were comparable across the intervention groups. The assessor of the outcome was aware of the assigned interventions in 39% (7/18) of the studies, but it was unlikely that the assessment of the outcome was influenced by knowledge of the intervention received in these studies. Accordingly, all studies (18/18, 100%) had a low risk of bias in the “measuring the outcome” domain ().

In total, 28% (5/18) of the studies published their protocols in sufficient detail. In all studies (18/18, 100%), the reported outcome measurements did not differ from those specified in the analysis plan, and there was no evidence that the studies selected their results from many results produced from multiple eligible analyses of the data. On the basis of these judgments, the risk of bias because of the selection of the reported results was considered low in 28% (5/18) of the studies ().

In the last domain, “overall bias,” the risk of bias was considered high in 22% (4/18) of the studies as they were judged as having a high risk of bias in at least one domain. A total of 61% (11/18) of the studies raised some concerns in the domain of overall bias as they had some issues in at least one of the domains and were not at high risk for any domain. The remaining 17% (3/18) of the studies were judged to be at low risk of bias for the domain of overall bias given that they were rated to be at low risk of bias for all domains. The reviewers’ judgments about each “risk of bias” domain for each included study are presented in [-].

‎Figure 2. Review authors’ judgments about each “risk of bias” domain. View this figureResults of the StudiesOverview

As mentioned earlier, the included studies assessed the effect of serious games on 3 outcomes: verbal, nonverbal, and working memory. The results of the included studies were divided into 3 groups based on these outcomes. Furthermore, the results for each outcome were grouped based on the comparator used in the studies (ie, control [no or passive interventions], conventional exercises, conventional cognitive activities, and other serious games).

Verbal MemorySerious Games Versus Control

The effect of serious games on verbal memory was compared with that of no or passive interventions in 44% (8/18) of the studies [,,,,-]. A total of 13% (1/8) of these studies were not included in the meta-analysis given that they did not report the required data and we could not obtain them when contacting the authors. Of the 7 studies included in the meta-analysis, 2 (29%) assessed verbal memory using 2 different measures [,]. Therefore, we included the results of all these measures in the meta-analysis to form 9 comparisons ( [,,,-]). The meta-analysis showed no statistically significant difference (P=.13) in verbal memory between the serious game and control groups (SMD=0.39, 95% CI −0.11 to 0.89). The statistical heterogeneity of the evidence was considerable (P<.001; I2=89.5%). The high heterogeneity may be attributed to differences in sample size, participants’ health condition, period of the intervention, and outcome measures among the studies included in this analysis. The quality of the evidence was very low as it was downgraded by 5 levels owing to a high risk of bias, heterogeneity, and imprecision ().

We conducted subgroup analyses, also known as moderator analyses [], to investigate whether different characteristics of the population (ie, sample size, health condition, and recruitment setting) and intervention (ie, delivery method, duration, frequency, and period) moderated the effect of serious games on verbal memory. As shown in , there was no statistically significant difference among all characteristics of the population and intervention except for the health condition of the participants (P=.003) and the period of the intervention (P=.05).

‎Figure 3. Forest plot of 7 studies (9 comparisons) comparing the effect of serious games with that of control on verbal memory. RE: random effect; SMD: standardized mean difference [,,,-]. View this figureSerious Games Versus Conventional Exercises

The effect of serious games was compared with that of conventional exercises in 17% (3/18) of the studies [,,] ( [,,]). A meta-analysis of the results of these studies showed a statistically significant difference in verbal memory (P=.003) between the groups, favoring serious games over conventional exercises (SMD=0.46, 95% CI 0.16-0.77). This difference was also clinically important as the overall effect was outside MCID boundaries (−0.23 to 0.23) and its 95% CI did not cross the “no effect” line (zero effect). For this outcome, the MCID boundaries were calculated as –0.5 times to +0.5 times the SMD value (0.46). The statistical heterogeneity of the evidence was not a concern (P=.34; I2=0%). The quality of the evidence was very low as it was downgraded by 3 levels owing to a high risk of bias and imprecision ().

‎Figure 4. Forest plot of 3 studies comparing the effect of serious games with that of conventional exercises on verbal memory. RE: random effect; SMD: standardized mean difference [,,]. View this figureSerious Games Versus Conventional Cognitive Activities

In total, 11% (2/18) of the studies examined the effect of serious games in comparison with conventional cognitive activities [,]. These studies assessed verbal memory using 2 different measures. Thus, we included the results of all these measures in a meta-analysis to form 4 comparisons ( [,]). The meta-analysis showed no statistically significant difference (P=.14) in verbal memory between the groups (SMD=0.66, 95% CI −0.21 to 1.54). The statistical heterogeneity of the evidence was substantial (P<.001; I2=76.3%). The high heterogeneity may be attributed to differences in the platform of the intervention, period of the intervention, and outcome measures among the studies included in this analysis. The quality of the evidence was very low as it was downgraded by 5 levels owing to a high risk of bias, heterogeneity, and imprecision ().

‎Figure 5. Forest plot of 2 studies (4 comparisons) comparing the effect of serious games with that of conventional cognitive activities on verbal memory. RE: random effect; SMD: standardized mean difference [,]. View this figureSerious Games Versus Other Serious Games

In total, 17% (3/18) of the studies compared the effect of serious games on verbal memory with that of other serious games [,,]. Specifically, Gooding et al [] compared the effect of a cognitive training game that included empirically validated motivational teaching and rehabilitation techniques (BrainFitnessPlus) with 2 other games: the same previous game without the aforementioned techniques (BrainFitness) and commercially available computer games and puzzles (ie, Brain Age, Sudoku, and crossword puzzles). The study found a statistically significant difference in memory between the groups, favoring BrainFitnessPlus and BrainFitness over commercially available computer games as measured by the Buschke Selective Reminding Test-Delay (BSRT-Delay) and the Wechsler Memory Scale Third Edition-Logical Memory II (WMS-III-LM-II) and favoring BrainFitness over commercially available computer games as measured by the BSRT-Delay only. However, there was no significant difference in memory between the BrainFitnessPlus and BrainFitness groups as measured by the BSRT-Delay and the WMS-III-LM-II [].

The second trial compared the effect of a cognitive training game with that of exergames []. The study found no statistically significant difference (P=.76) in memory between the groups. The last study in this group compared the effect of a cognitive training game that adjusts the level of difficulty of the tasks based on an individual’s mastery on each level (ie, adaptive game) with the same game but without adjustment of the level of difficulty of the tasks (ie, nonadaptive game) []. The study showed no statistically significant difference between the groups as measured by the WMS-III-LM-II (P=.76) and the California Verbal Learning Test Total Hits (P=.30), but there was a statistically significant difference between the groups as measured by the California Verbal Learning Test II Long Delay Free Recall (P=.03), favoring the adaptive game over the nonadaptive game [].

Nonverbal MemorySerious Games V