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<article xmlns:xlink="http://www.w3.org/1999/xlink" article-type="review-article" dtd-version="2.0">
  <front>
    <journal-meta>
      <journal-id journal-id-type="publisher-id">JSG</journal-id>
      <journal-id journal-id-type="nlm-ta">JMIR Serious Games</journal-id>
      <journal-title>JMIR Serious Games</journal-title>
      <issn pub-type="epub">2291-9279</issn>
      <publisher>
        <publisher-name>JMIR Publications</publisher-name>
        <publisher-loc>Toronto, Canada</publisher-loc>
      </publisher>
    </journal-meta>
    <article-meta>
      <article-id pub-id-type="publisher-id">v10i3e36754</article-id>
      <article-id pub-id-type="pmid">36083623</article-id>
      <article-id pub-id-type="doi">10.2196/36754</article-id>
      <article-categories>
        <subj-group subj-group-type="heading">
          <subject>Review</subject>
        </subj-group>
        <subj-group subj-group-type="article-type">
          <subject>Review</subject>
        </subj-group>
      </article-categories>
      <title-group>
        <article-title>The Effectiveness of Serious Games on Cognitive Processing Speed Among Older Adults With Cognitive Impairment: Systematic Review and Meta-analysis</article-title>
      </title-group>
      <contrib-group>
        <contrib contrib-type="editor">
          <name>
            <surname>Zary</surname>
            <given-names>Nabil</given-names>
          </name>
        </contrib>
      </contrib-group>
      <contrib-group>
        <contrib contrib-type="reviewer">
          <name>
            <surname>Al-Jafar</surname>
            <given-names>Eiman</given-names>
          </name>
        </contrib>
        <contrib contrib-type="reviewer">
          <name>
            <surname>Alajlani</surname>
            <given-names>Mohannad</given-names>
          </name>
        </contrib>
        <contrib contrib-type="reviewer">
          <name>
            <surname>Khalifa</surname>
            <given-names>Mohamed</given-names>
          </name>
        </contrib>
      </contrib-group>
      <contrib-group>
        <contrib id="contrib1" contrib-type="author">
          <name name-style="western">
            <surname>Abd-alrazaq</surname>
            <given-names>Alaa</given-names>
          </name>
          <degrees>PhD</degrees>
          <xref rid="aff1" ref-type="aff">1</xref>
          <ext-link ext-link-type="orcid">https://orcid.org/0000-0001-7695-4626</ext-link>
        </contrib>
        <contrib id="contrib2" contrib-type="author">
          <name name-style="western">
            <surname>Ahmed</surname>
            <given-names>Arfan</given-names>
          </name>
          <degrees>PhD</degrees>
          <xref rid="aff1" ref-type="aff">1</xref>
          <ext-link ext-link-type="orcid">https://orcid.org/0000-0002-4025-5767</ext-link>
        </contrib>
        <contrib id="contrib3" contrib-type="author">
          <name name-style="western">
            <surname>Alali</surname>
            <given-names>Haitham</given-names>
          </name>
          <degrees>PhD</degrees>
          <xref rid="aff2" ref-type="aff">2</xref>
          <ext-link ext-link-type="orcid">https://orcid.org/0000-0001-9367-0078</ext-link>
        </contrib>
        <contrib id="contrib4" contrib-type="author">
          <name name-style="western">
            <surname>Aldardour</surname>
            <given-names>Ahmad Mohammad</given-names>
          </name>
          <degrees>MSc</degrees>
          <xref rid="aff3" ref-type="aff">3</xref>
          <ext-link ext-link-type="orcid">https://orcid.org/0000-0001-9924-9460</ext-link>
        </contrib>
        <contrib id="contrib5" contrib-type="author" corresp="yes">
          <name name-style="western">
            <surname>Househ</surname>
            <given-names>Mowafa</given-names>
          </name>
          <degrees>PhD</degrees>
          <xref rid="aff4" ref-type="aff">4</xref>
          <address>
            <institution>Division of Information and Computing Technology, College of Science and Engineering</institution>
            <institution>Hamad Bin Khalifa University</institution>
            <institution>Qatar Foundation</institution>
            <addr-line>PO Box 34110</addr-line>
            <addr-line>Doha Al Luqta St, Ar-Rayyan</addr-line>
            <addr-line>Doha, 0000</addr-line>
            <country>Qatar</country>
            <phone>974 55708549</phone>
            <email>mhouseh@hbku.edu.qa</email>
          </address>
          <ext-link ext-link-type="orcid">https://orcid.org/0000-0002-3648-6271</ext-link>
        </contrib>
      </contrib-group>
      <aff id="aff1">
        <label>1</label>
        <institution>AI Center for Precision Health</institution>
        <institution>Weill Cornell Medicine-Qatar</institution>
        <addr-line>Doha</addr-line>
        <country>Qatar</country>
      </aff>
      <aff id="aff2">
        <label>2</label>
        <institution>Health Management Department, Faculty of Medical and Health Sciences</institution>
        <institution>Liwa College of Technology</institution>
        <addr-line>Abu Dhabi</addr-line>
        <country>United Arab Emirates</country>
      </aff>
      <aff id="aff3">
        <label>3</label>
        <institution>Physical Therapy Department</institution>
        <institution>Rumailah Hospital</institution>
        <institution>Hamad Medical Corporation</institution>
        <addr-line>Doha</addr-line>
        <country>Qatar</country>
      </aff>
      <aff id="aff4">
        <label>4</label>
        <institution>Division of Information and Computing Technology, College of Science and Engineering</institution>
        <institution>Hamad Bin Khalifa University</institution>
        <institution>Qatar Foundation</institution>
        <addr-line>Doha</addr-line>
        <country>Qatar</country>
      </aff>
      <author-notes>
        <corresp>Corresponding Author: Mowafa Househ <email>mhouseh@hbku.edu.qa</email></corresp>
      </author-notes>
      <pub-date pub-type="collection">
        <season>Jul-Sep</season>
        <year>2022</year>
      </pub-date>
      <pub-date pub-type="epub">
        <day>9</day>
        <month>9</month>
        <year>2022</year>
      </pub-date>
      <volume>10</volume>
      <issue>3</issue>
      <elocation-id>e36754</elocation-id>
      <history>
        <date date-type="received">
          <day>29</day>
          <month>1</month>
          <year>2022</year>
        </date>
        <date date-type="rev-request">
          <day>16</day>
          <month>3</month>
          <year>2022</year>
        </date>
        <date date-type="rev-recd">
          <day>23</day>
          <month>3</month>
          <year>2022</year>
        </date>
        <date date-type="accepted">
          <day>7</day>
          <month>4</month>
          <year>2022</year>
        </date>
      </history>
      <copyright-statement>©Alaa Abd-alrazaq, Arfan Ahmed, Haitham Alali, Ahmad Mohammad Aldardour, Mowafa Househ. Originally published in JMIR Serious Games (https://games.jmir.org), 09.09.2022.</copyright-statement>
      <copyright-year>2022</copyright-year>
      <license license-type="open-access" xlink:href="https://creativecommons.org/licenses/by/4.0/">
        <p>This is an open-access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work, first published in JMIR Serious Games, is properly cited. The complete bibliographic information, a link to the original publication on https://games.jmir.org, as well as this copyright and license information must be included.</p>
      </license>
      <self-uri xlink:href="https://games.jmir.org/2022/3/e36754" xlink:type="simple"/>
      <abstract>
        <sec sec-type="background">
          <title>Background</title>
          <p>Human cognitive processing speed is known to decline with age. Human cognitive processing speed refers to the time that an individual takes from receiving a stimulus to reacting to it. Serious games, which are video games used for training and educational purposes, have the potential to improve processing speed. Numerous systematic reviews have summarized the evidence regarding the effectiveness of serious games in improving processing speed, but they are undermined by some limitations.</p>
        </sec>
        <sec sec-type="objective">
          <title>Objective</title>
          <p>This study aimed to examine the effectiveness of serious games on the cognitive processing speed of an older adult population living with cognitive impairment.</p>
        </sec>
        <sec sec-type="methods">
          <title>Methods</title>
          <p>A systematic review of randomized controlled trials (RCTs) was conducted. Two search sources were used in this review: 8 electronic databases and backward and forward reference list checking. A total of 2 reviewers independently checked the eligibility of the studies, extracted data from the included studies, and appraised the risk of bias and quality of the evidence. Evidence from the included studies was synthesized using a narrative and statistical approach (ie, meta-analysis), as appropriate.</p>
        </sec>
        <sec sec-type="results">
          <title>Results</title>
          <p>Of the 548 publications identified, 16 (2.9%) RCTs eventually met all eligibility criteria. Very-low-quality evidence from 50% (8/16) and 38% (6/16) of the RCTs showed no statistically significant effect of serious games on processing speed compared with no or passive intervention groups (<italic>P</italic>=.77) and conventional exercises (<italic>P</italic>=.58), respectively. A subgroup analysis showed that both types of serious games (cognitive training games: <italic>P</italic>=.26; exergames: <italic>P</italic>=.88) were as effective as conventional exercises in improving processing speed.</p>
        </sec>
        <sec sec-type="conclusions">
          <title>Conclusions</title>
          <p>There is no superiority of serious games over no or passive interventions and conventional exercises in improving processing speed among older adults with cognitive impairment. However, our findings remain inconclusive because of the low quality of the evidence, the small sample size in most of the included studies, and the paucity of studies included in the meta-analyses. Therefore, until more robust evidence is published, serious games should be offered or used as an adjunct to existing interventions. Further trials should be undertaken to investigate the effect of serious games that specifically target processing speed rather than cognitive abilities in general.</p>
        </sec>
        <sec sec-type="Trial Registration">
          <title>Trial Registration</title>
          <p>PROSPERO CRD42022301667; https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=301667</p>
        </sec>
      </abstract>
      <kwd-group>
        <kwd>serious games</kwd>
        <kwd>cognitive training</kwd>
        <kwd>exergames</kwd>
        <kwd>processing speed</kwd>
        <kwd>mild cognitive impairment</kwd>
        <kwd>Alzheimer disease</kwd>
        <kwd>dementia</kwd>
        <kwd>systematic reviews</kwd>
        <kwd>meta-analysis</kwd>
        <kwd>mobile phone</kwd>
      </kwd-group>
    </article-meta>
  </front>
  <body>
    <sec sec-type="introduction">
      <title>Introduction</title>
      <sec>
        <title>Background</title>
        <p>By 2050, the older adult population is expected to double on a global scale [<xref ref-type="bibr" rid="ref1">1</xref>] followed by a growing demand for high-quality support among this population. There is a variety of disabilities related to aging. However, a considerable percentage of people aged &#62;65 years are affected by cognitive impairments. According to the Alzheimer’s Association, approximately 15% to 20% of people aged &#62;65 years are affected by mild cognitive impairment (MCI) [<xref ref-type="bibr" rid="ref2">2</xref>]. It is a progressive, terminal brain disorder for which the cure and cause are unknown [<xref ref-type="bibr" rid="ref3">3</xref>]. Worldwide, the number of Alzheimer disease (AD) cases is rising; estimates indicate that 44 million people currently have AD or dementia. As the Baby Boomer generation passes the age of 65 years, the number of people experiencing AD is expected to reach 76 million by 2030 [<xref ref-type="bibr" rid="ref4">4</xref>,<xref ref-type="bibr" rid="ref5">5</xref>]. The consequences of these cognitive disorders include poor judgment, decreased activity, and memory loss. They are difficult to manage; thus, it would be highly beneficial to develop proper and effective interventions for the older adult population.</p>
        <p>These disorders imply a decline in various cognitive functions such as memory [<xref ref-type="bibr" rid="ref6">6</xref>,<xref ref-type="bibr" rid="ref7">7</xref>], executive function [<xref ref-type="bibr" rid="ref8">8</xref>,<xref ref-type="bibr" rid="ref9">9</xref>], attention [<xref ref-type="bibr" rid="ref10">10</xref>], and processing speed [<xref ref-type="bibr" rid="ref11">11</xref>]. Processing speed refers to the time that an individual takes from receiving a stimulus to reacting to it. Slowed processing speed is a typical characteristic of cognitive aging. It implies a slowing rate at which individuals perform decision-making as well as motor and perceptual tasks. Moreover, processing speed represents one of the critical predictors of performance related to cognitive tasks in older adults; it is the basis of a primary hypothesis for age-related cognitive decline [<xref ref-type="bibr" rid="ref11">11</xref>,<xref ref-type="bibr" rid="ref12">12</xref>]. Accordingly, aging research primarily aims to design methods for improving and maintaining cognitive functions in older adults.</p>
        <p>Serious games are one of the interventions that have been used to improve and maintain processing speed in older adults. Serious games represent a type of video game used for training and educational purposes in different contexts [<xref ref-type="bibr" rid="ref13">13</xref>,<xref ref-type="bibr" rid="ref14">14</xref>]. Serious games have shown promising results in improving cognitive functions such as global cognition [<xref ref-type="bibr" rid="ref15">15</xref>-<xref ref-type="bibr" rid="ref18">18</xref>], processing speed [<xref ref-type="bibr" rid="ref16">16</xref>-<xref ref-type="bibr" rid="ref20">20</xref>], memory [<xref ref-type="bibr" rid="ref16">16</xref>-<xref ref-type="bibr" rid="ref23">23</xref>], executive function [<xref ref-type="bibr" rid="ref16">16</xref>-<xref ref-type="bibr" rid="ref22">22</xref>,<xref ref-type="bibr" rid="ref24">24</xref>], and attention [<xref ref-type="bibr" rid="ref16">16</xref>,<xref ref-type="bibr" rid="ref17">17</xref>,<xref ref-type="bibr" rid="ref19">19</xref>,<xref ref-type="bibr" rid="ref20">20</xref>,<xref ref-type="bibr" rid="ref22">22</xref>]. The most common types of serious games used for improving cognitive abilities are exergames (video games that require physical exercise as part of playing) and cognitive training games (video games that include cognitively stimulating activities designed to maintain or promote the users’ cognitive abilities).</p>
      </sec>
      <sec>
        <title>Research Gap and Aim</title>
        <p>Several studies have explored the therapeutic impact of serious games on processing speed. However, the evidence from these studies is still fragmented. Aggregating the evidence through systematic reviews is important to draw conclusions about the effectiveness of serious games in improving processing speed. A total of 5 systematic reviews have pooled findings from these studies, but they are undermined by some limitations [<xref ref-type="bibr" rid="ref16">16</xref>-<xref ref-type="bibr" rid="ref20">20</xref>]. Specifically, these reviews (1) focused on older adults without cognitive impairment [<xref ref-type="bibr" rid="ref16">16</xref>,<xref ref-type="bibr" rid="ref18">18</xref>-<xref ref-type="bibr" rid="ref20">20</xref>], (2) included quasi-experiments or pilot randomized controlled trials (RCTs) [<xref ref-type="bibr" rid="ref17">17</xref>-<xref ref-type="bibr" rid="ref19">19</xref>], (3) did not assess the quality of the meta-analyzed evidence [<xref ref-type="bibr" rid="ref17">17</xref>,<xref ref-type="bibr" rid="ref18">18</xref>,<xref ref-type="bibr" rid="ref20">20</xref>], (4) only focused on a specific type of serious game such as cognitive training games [<xref ref-type="bibr" rid="ref16">16</xref>,<xref ref-type="bibr" rid="ref17">17</xref>,<xref ref-type="bibr" rid="ref20">20</xref>] and exergames [<xref ref-type="bibr" rid="ref18">18</xref>], or (5) did not compare the effect of serious games with a specific comparator (eg, no intervention, conventional exercises, or conventional cognitive activities) [<xref ref-type="bibr" rid="ref16">16</xref>-<xref ref-type="bibr" rid="ref18">18</xref>,<xref ref-type="bibr" rid="ref20">20</xref>]. Accordingly, the aim of this review was to examine the effectiveness of serious games on the cognitive processing speed of an older adult population living with cognitive impairment. To address the aforementioned limitations, we (1) focused on older adults with cognitive impairment; (2) included only RCTs; (3) appraised the quality of the meta-analyzed evidence using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach; (4) included all types of serious games; and (5) compared the effect of serious games with that of a specific comparator. In this review, effectiveness refers to the degree to which serious games are successful in improving cognitive processing speed.</p>
      </sec>
    </sec>
    <sec sec-type="methods">
      <title>Methods</title>
      <p>To conduct this systematic review, we followed the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines (<xref ref-type="supplementary-material" rid="app1">Multimedia Appendix 1</xref>) [<xref ref-type="bibr" rid="ref25">25</xref>]. The protocol for this review is registered at PROSPERO (ID: CRD42022301667).</p>
      <sec>
        <title>Search Strategy</title>
        <sec>
          <title>Search Sources</title>
          <p>The first author searched the following databases on November 10, 2021: MEDLINE (via Ovid), PsycINFO (via Ovid), Embase (via Ovid), CINAHL (via EBSCO), IEEE Xplore, ACM Digital Library, Scopus, and Google Scholar. Only the first 10 pages (ie, 100 hits) were considered as the databases return a large number of studies automatically ordered according to relevance [<xref ref-type="bibr" rid="ref26">26</xref>]. Finally, backward reference list checking (ie, screening the reference lists of the included studies and relevant reviews) and forward reference list checking (ie, screening the studies that cited the included studies) were conducted.</p>
        </sec>
        <sec>
          <title>Search Terms</title>
          <p>The search query was developed in consultation with 2 experts in digital mental health. It included terms related to the target population (eg, cognitive disorder), target intervention (eg, serious games), and targeted study design (eg, RCTs). <xref ref-type="supplementary-material" rid="app2">Multimedia Appendix 2</xref> summarizes the search query that was used for each of the 8 databases.</p>
        </sec>
      </sec>
      <sec>
        <title>Study Eligibility Criteria</title>
        <p>Only RCTs that evaluated the effectiveness of serious games in improving processing speed among older adults with cognitive impairment were included in this study. To be more precise, we considered studies that included serious games available on any digital platform, such as PCs, video game consoles (eg, Xbox and PlayStation), mobile phones, tablets, handheld devices, Nintendo, or any other type of digital device. The game had to be the major component of the intervention and used solely for therapeutic purposes. Studies involving serious games in combination with other interventions were included if the control group underwent the same adjacent intervention. Games that were not based on digital technology (eg, paper-and-pencil games and board games) or that were used for monitoring, screening, diagnosis, or research were excluded.</p>
        <p>The study population was older adults (aged ≥60 years) with any type of cognitive impairment or disorder as confirmed by checking the inclusion criteria or baseline scores against defined diagnostic criteria (eg, Mini-Mental State Examination). Older adults without cognitive impairment, health care providers, and caregivers were beyond the scope of this review. No restrictions were applied regarding gender or ethnicity.</p>
        <p>The outcome of interest in this review was cognitive processing speed. No restrictions were applied regarding the outcome measures. This review did not consider studies that focused only on cost-effectiveness, acceptance, feasibility, satisfaction, or cognitive abilities other than processing speed. The focus of this review was on postintervention data (ie, outcome data collected just after the intervention) rather than follow-up data (ie, outcome data collected a period after the intervention).</p>
        <p>All types of RCTs (ie, parallel, cluster, crossover, and factorial) were considered in this review, whereas pilot RCTs, quasi-experiments, observational studies, and reviews were excluded. We included journal articles, conference proceedings, and dissertations, whereas abstracts, conference posters, commentaries, proposals, and editorials were excluded. This review was restricted to only studies written in the English language and published since 2010. We did not apply restrictions on the country of publication, comparator, or study settings.</p>
      </sec>
      <sec>
        <title>Study Selection</title>
        <p>We identified relevant studies by using the following process. First, all the retrieved studies were imported into EndNote (Clarivate Analytics) to find duplicate publications and remove them. Second, the titles and abstracts of all the retrieved studies were checked by 2 reviewers working independently (the first and second authors). Finally, both reviewers independently read the complete texts of the studies included in the previous step. Any disagreements were resolved via discussion. Steps 2 and 3 had an interrater agreement (Cohen κ) of 0.88 and 0.96, respectively.</p>
      </sec>
      <sec>
        <title>Data Extraction</title>
        <p>Before extracting the data, we pilot-tested the data extraction form with 2 of the included studies. Microsoft Excel was used by 2 reviewers (the first and second authors) to independently extract data from the included studies. Any disputes in the extracted data between the reviewers were resolved through discussion. The first and corresponding authors of the included studies were contacted to retrieve outcome data (eg, mean, SD, and sample size) if they were missing from the published articles. The data extraction form is provided in <xref ref-type="supplementary-material" rid="app3">Multimedia Appendix 3</xref>.</p>
      </sec>
      <sec>
        <title>Risk of Bias Appraisal</title>
        <p>Two reviewers (the first and second authors) independently examined the risk of bias in the included studies using the Risk of Bias 2 tool [<xref ref-type="bibr" rid="ref27">27</xref>]. This tool evaluates the risk of bias in 5 areas of RCTs: randomization process, deviations from intended interventions, missing outcome data, measurement of the outcome, and selection of the results [<xref ref-type="bibr" rid="ref27">27</xref>]. The reviewers held discussions to resolve any disagreements, and the interrater agreement was 0.85.</p>
      </sec>
      <sec>
        <title>Data Synthesis</title>
        <p>Narrative and statistical methods were used to summarize the collected data. In our narrative synthesis, we used text and tables to describe the characteristics of the included studies (study metadata, population, interventions, comparisons, and outcome measures). The results of the experiments were compiled and classified according to the comparator: no or passive interventions, conventional exercises, and other serious games. When 2 or more studies from the same comparator submitted sufficient data (ie, mean, SD, and number of participants in each intervention group), meta-analyses were performed using Review Manager (RevMan 5.4; The Cochrane Collaboration). As the type of data for the outcome of interest (processing speed) was continuous and the instruments used to evaluate the outcome varied across the included trials, the standardized mean difference (SMD; Cohen <italic>d</italic>) was used to estimate the overall effect of each study. We also chose the random effects model for the analysis because of the high clinical heterogeneity among the meta-analyzed trials 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).</p>
        <p>To assess the degree and statistical significance of heterogeneity in the meta-analyzed studies, we calculated <italic>I</italic><sup>2</sup> and a chi-square <italic>P</italic> value, respectively. A chi-square <italic>P</italic> value of ≤.05 indicated heterogeneous meta-analyzed studies [<xref ref-type="bibr" rid="ref28">28</xref>]. When <italic>I</italic><sup>2</sup> ranged from 0% to 40%, 30% to 60%, 50% to 90%, and 75% to 100%, the degree of heterogeneity was considered as insignificant, moderate, substantial, or considerable, respectively [<xref ref-type="bibr" rid="ref28">28</xref>].</p>
        <p>We used the GRADE approach [<xref ref-type="bibr" rid="ref29">29</xref>] to appraise the overall quality of the evidence resulting from the meta-analyses. The GRADE approach examines the quality of evidence based on 5 domains: risk of bias, inconsistency (ie, heterogeneity), indirectness, imprecision, and publication bias [<xref ref-type="bibr" rid="ref29">29</xref>]. The quality of the meta-analyzed evidence was independently assessed by 2 reviewers (the first and second authors). Any differences between the reviewers were resolved via discussion, and the interrater agreement of the reviewers was 0.94 [<xref ref-type="bibr" rid="ref30">30</xref>].</p>
      </sec>
    </sec>
    <sec sec-type="results">
      <title>Results</title>
      <sec>
        <title>Search Results</title>
        <p>As shown in <xref rid="figure1" ref-type="fig">Figure 1</xref>, a total of 548 records were found after searching 8 electronic databases. Using the EndNote software, of the 548 records, 98 (17.9%) duplicates were removed. Checking the titles and abstracts of the remaining records resulted in the exclusion of 63.1% (346/548) for several reasons shown in <xref rid="figure1" ref-type="fig">Figure 1</xref>. Reading the full text of the remaining 104 publications resulted in the exclusion of 88 (84.6%) studies (<xref rid="figure1" ref-type="fig">Figure 1</xref>). This review included 16 RCTs in total [<xref ref-type="bibr" rid="ref31">31</xref>-<xref ref-type="bibr" rid="ref46">46</xref>]. Of these 16 RCTs, 13 (81%) were included in the meta-analyses [<xref ref-type="bibr" rid="ref31">31</xref>-<xref ref-type="bibr" rid="ref43">43</xref>].</p>
        <fig id="figure1" position="float">
          <label>Figure 1</label>
          <caption>
            <p>Flowchart of the study selection process.</p>
          </caption>
          <graphic xlink:href="games_v10i3e36754_fig1.png" alt-version="no" mimetype="image" position="float" xlink:type="simple"/>
        </fig>
      </sec>
      <sec>
        <title>Characteristics of the Included Studies</title>
        <p>The included studies were published between 2012 and 2021 and came from 11 different countries (<xref ref-type="table" rid="table1">Table 1</xref>). Except for a book chapter, all the included papers (15/16, 94%) were peer-reviewed articles. Parallel RCTs were the most common type of trial used in the included studies (14/16, 88%). The sample sizes of the included studies ranged from 20 to 195, with an average of 79.9. The average age of the participants was reported in 94% (15/16) of the studies and varied between 66 and 82.9 years, with an average of 75 years. Male participants in 94% (15/16) of the studies ranged from 23.5% to 71%, with an average of 47.5%. The mean Mini-Mental State Examination score of the participants was reported in 88% (14/16) of the studies and ranged from 18.6 to 28.1, with an average of 24.4. The most common disorder among the participants in the included studies was MCI (11/16, 69%). Participants were drawn from clinical (10/16, 62%), community (4/16, 25%), and clinical and community (2/16, 12%) settings.</p>
        <table-wrap position="float" id="table1">
          <label>Table 1</label>
          <caption>
            <p>Characteristics of the studies and populations (N=16).</p>
          </caption>
          <table width="1000" cellpadding="5" cellspacing="0" border="1" rules="groups" frame="hsides">
            <col width="120"/>
            <col width="100"/>
            <col width="120"/>
            <col width="80"/>
            <col width="80"/>
            <col width="100"/>
            <col width="100"/>
            <col width="80"/>
            <col width="120"/>
            <col width="100"/>
            <thead>
              <tr valign="top">
                <td>Study, year</td>
                <td>Country</td>
                <td>Publication type</td>
                <td>RCT<sup>a</sup> type</td>
                <td>Sample size</td>
                <td>Age, mean (SD)</td>
                <td>Male participants, n (%)</td>
                <td>MMSE<sup>b</sup> score</td>
                <td>Health condition</td>
                <td>Setting</td>
              </tr>
            </thead>
            <tbody>
              <tr valign="top">
                <td>Finn and McDonald [<xref ref-type="bibr" rid="ref31">31</xref>], 2015</td>
                <td>Australia</td>
                <td>Journal article</td>
                <td>Parallel</td>
                <td>31</td>
                <td>75.6</td>
                <td>22 (71)</td>
                <td>28.1</td>
                <td>MCI<sup>c</sup></td>
                <td>Clinical</td>
              </tr>
              <tr valign="top">
                <td>Robert et al [<xref ref-type="bibr" rid="ref32">32</xref>], 2020</td>
                <td>France</td>
                <td>Journal article</td>
                <td>Parallel</td>
                <td>46</td>
                <td>79.4</td>
                <td>22 (47.8)</td>
                <td>21.4</td>
                <td>Neurocognitive disorders</td>
                <td>Clinical</td>
              </tr>
              <tr valign="top">
                <td>Savulich et al [<xref ref-type="bibr" rid="ref33">33</xref>], 2017</td>
                <td>United Kingdom</td>
                <td>Journal article</td>
                <td>Parallel</td>
                <td>42</td>
                <td>76.1</td>
                <td>25 (59.5)</td>
                <td>26.7</td>
                <td>MCI</td>
                <td>Clinical</td>
              </tr>
              <tr valign="top">
                <td>Valdes et al [<xref ref-type="bibr" rid="ref34">34</xref>], 2012</td>
                <td>United States</td>
                <td>Journal article</td>
                <td>Parallel</td>
                <td>195</td>
                <td>77.7</td>
                <td>65 (33.3)</td>
                <td>NR<sup>d</sup></td>
                <td>MCI</td>
                <td>Clinical</td>
              </tr>
              <tr valign="top">
                <td>Yang and Kwak [<xref ref-type="bibr" rid="ref35">35</xref>], 2017</td>
                <td>South Korea</td>
                <td>Journal article</td>
                <td>Parallel</td>
                <td>20</td>
                <td>71</td>
                <td>14 (70)</td>
                <td>23.1</td>
                <td>AD<sup>e</sup></td>
                <td>Clinical</td>
              </tr>
              <tr valign="top">
                <td>Thapa et al [<xref ref-type="bibr" rid="ref36">36</xref>], 2020</td>
                <td>South Korea</td>
                <td>Journal article</td>
                <td>Parallel</td>
                <td>68</td>
                <td>72.7</td>
                <td>16 (23.5)</td>
                <td>26.2</td>
                <td>MCI</td>
                <td>Clinical</td>
              </tr>
              <tr valign="top">
                <td>Tarnanas et al [<xref ref-type="bibr" rid="ref37">37</xref>], 2014</td>
                <td>Greece</td>
                <td>Book chapter</td>
                <td>Parallel</td>
                <td>114</td>
                <td>70.3</td>
                <td>44 (39)</td>
                <td>26.4</td>
                <td>MCI</td>
                <td>Clinical</td>
              </tr>
              <tr valign="top">
                <td>Fiatarone Singh et al [<xref ref-type="bibr" rid="ref38">38</xref>], 2014</td>
                <td>Australia</td>
                <td>Journal article</td>
                <td>Factorial</td>
                <td>100</td>
                <td>70.1</td>
                <td>32 (32)</td>
                <td>27</td>
                <td>MCI</td>
                <td>Community</td>
              </tr>
              <tr valign="top">
                <td>Amjad et al [<xref ref-type="bibr" rid="ref39">39</xref>], 2019</td>
                <td>Pakistan</td>
                <td>Journal article</td>
                <td>Parallel</td>
                <td>44</td>
                <td>NR</td>
                <td>NR</td>
                <td>24</td>
                <td>MCI</td>
                <td>Clinical</td>
              </tr>
              <tr valign="top">
                <td>Wiloth et al [<xref ref-type="bibr" rid="ref40">40</xref>], 2017</td>
                <td>Germany</td>
                <td>Journal article</td>
                <td>Parallel</td>
                <td>99</td>
                <td>82.9</td>
                <td>28 (28.3)</td>
                <td>22</td>
                <td>Dementia</td>
                <td>Clinical and community</td>
              </tr>
              <tr valign="top">
                <td>Van Santen et al [<xref ref-type="bibr" rid="ref41">41</xref>], 2020</td>
                <td>Netherlands</td>
                <td>Journal article</td>
                <td>Cluster</td>
                <td>112</td>
                <td>79</td>
                <td>60 (53.5)</td>
                <td>18.6</td>
                <td>Dementia</td>
                <td>Clinical</td>
              </tr>
              <tr valign="top">
                <td>Karssemeijer et al [<xref ref-type="bibr" rid="ref42">42</xref>], 2019</td>
                <td>Netherlands</td>
                <td>Journal article</td>
                <td>Parallel</td>
                <td>115</td>
                <td>79.9</td>
                <td>62 (53.9)</td>
                <td>22.4</td>
                <td>Dementia</td>
                <td>Clinical and community</td>
              </tr>
              <tr valign="top">
                <td>Liao et al [<xref ref-type="bibr" rid="ref43">43</xref>], 2021</td>
                <td>Taiwan</td>
                <td>Journal article</td>
                <td>Parallel</td>
                <td>61</td>
                <td>81.5</td>
                <td>20 (32.6)</td>
                <td>22.9</td>
                <td>MCI</td>
                <td>Community</td>
              </tr>
              <tr valign="top">
                <td>Flak et al [<xref ref-type="bibr" rid="ref44">44</xref>], 2019</td>
                <td>Norway</td>
                <td>Journal article</td>
                <td>Parallel</td>
                <td>85</td>
                <td>66</td>
                <td>57 (66.7)</td>
                <td>NR</td>
                <td>MCI</td>
                <td>Clinical</td>
              </tr>
              <tr valign="top">
                <td>Hyer et al [<xref ref-type="bibr" rid="ref45">45</xref>], 2016</td>
                <td>United States</td>
                <td>Journal article</td>
                <td>Parallel</td>
                <td>68</td>
                <td>75.2</td>
                <td>32 (47.1)</td>
                <td>26</td>
                <td>MCI</td>
                <td>Community</td>
              </tr>
              <tr valign="top">
                <td>Park and Park [<xref ref-type="bibr" rid="ref46">46</xref>], 2017</td>
                <td>South Korea</td>
                <td>Journal article</td>
                <td>Parallel</td>
                <td>78</td>
                <td>67.3</td>
                <td>42 (53.8)</td>
                <td>26.5</td>
                <td>MCI</td>
                <td>Community</td>
              </tr>
            </tbody>
          </table>
          <table-wrap-foot>
            <fn id="table1fn1">
              <p><sup>a</sup>RCT: randomized controlled trial.</p>
            </fn>
            <fn id="table1fn2">
              <p><sup>b</sup>MMSE: Mini-Mental State Examination.</p>
            </fn>
            <fn id="table1fn3">
              <p><sup>c</sup>MCI: mild cognitive impairment.</p>
            </fn>
            <fn id="table1fn4">
              <p><sup>d</sup>NR: not reported.</p>
            </fn>
            <fn id="table1fn5">
              <p><sup>e</sup>AD: Alzheimer disease.</p>
            </fn>
          </table-wrap-foot>
        </table-wrap>
        <p>We identified 16 distinct serious games used in the studies (<xref ref-type="table" rid="table2">Table 2</xref>). More than one game was used in 6% (1/16) of the studies. The serious games in the trials were divided into 2 categories based on the treatment modality they provided: cognitive training games (12/16, 75%) and exergames (4/16, 25%). In 88% (14/16) of the studies, the games were designed with a “serious” objective from the start (designed serious games). By contrast, games in the remaining 12% (2/16) of the studies were not planned as serious games from the start but were instead used for a serious purpose (purpose-shifted games). Serious games were played under the supervision of health care providers or caregivers in most studies (11/16, 69%). The game duration in the included studies ranged from 25 to 100 minutes. The frequency of playing the games ranged from 2 to 7 times per week, but it was &#60;4 times per week in approximately two-thirds of the studies (11/16, 69%). The duration of the interventions ranged from 4 to 25 weeks, but it was &#60;13 weeks in three-fourths of the studies (13/16, 81%).</p>
        <table-wrap position="float" id="table2">
          <label>Table 2</label>
          <caption>
            <p>Characteristics of the interventions (N=16).</p>
          </caption>
          <table width="1000" cellpadding="5" cellspacing="0" border="1" rules="groups" frame="hsides">
            <col width="130"/>
            <col width="120"/>
            <col width="120"/>
            <col width="100"/>
            <col width="110"/>
            <col width="120"/>
            <col width="100"/>
            <col width="100"/>
            <col width="100"/>
            <thead>
              <tr valign="top">
                <td>Study</td>
                <td>Serious game name</td>
                <td>Serious game type</td>
                <td>Serious game genre</td>
                <td>Platform</td>
                <td>Supervision</td>
                <td>Duration (minutes)</td>
                <td>Frequency (times per week)</td>
                <td>Period (weeks)</td>
              </tr>
            </thead>
            <tbody>
              <tr valign="top">
                <td>Finn and McDonald [<xref ref-type="bibr" rid="ref31">31</xref>]</td>
                <td>E-Prime</td>
                <td>Cognitive training game</td>
                <td>Designed</td>
                <td>PC</td>
                <td>Supervised</td>
                <td>NR<sup>a</sup></td>
                <td>2</td>
                <td>4</td>
              </tr>
              <tr valign="top">
                <td>Robert et al [<xref ref-type="bibr" rid="ref32">32</xref>]</td>
                <td>MeMo</td>
                <td>Cognitive training game</td>
                <td>Designed</td>
                <td>PC and tablet</td>
                <td>Unsupervised</td>
                <td>30</td>
                <td>4</td>
                <td>12</td>
              </tr>
              <tr valign="top">
                <td>Savulich et al [<xref ref-type="bibr" rid="ref33">33</xref>]</td>
                <td>Game Show</td>
                <td>Cognitive training game</td>
                <td>Designed</td>
                <td>Tablet</td>
                <td>Supervised</td>
                <td>60</td>
                <td>2</td>
                <td>4</td>
              </tr>
              <tr valign="top">
                <td>Valdes et al [<xref ref-type="bibr" rid="ref34">34</xref>]</td>
                <td>SOPT</td>
                <td>Cognitive training game</td>
                <td>Designed</td>
                <td>PC</td>
                <td>Supervised</td>
                <td>60</td>
                <td>2</td>
                <td>5</td>
              </tr>
              <tr valign="top">
                <td>Yang and Kwak [<xref ref-type="bibr" rid="ref35">35</xref>]</td>
                <td>Brain-Care</td>
                <td>Cognitive training game</td>
                <td>Designed</td>
                <td>PC</td>
                <td>Unsupervised</td>
                <td>60</td>
                <td>2</td>
                <td>12</td>
              </tr>
              <tr valign="top">
                <td>Thapa et al [<xref ref-type="bibr" rid="ref36">36</xref>]</td>
                <td>Juice Making, Crow Shooting, Love House, and Fireworks</td>
                <td>Cognitive training game</td>
                <td>Designed</td>
                <td>VR<sup>b</sup> headset and hand controllers</td>
                <td>Supervised</td>
                <td>100</td>
                <td>3</td>
                <td>8</td>
              </tr>
              <tr valign="top">
                <td>Tarnanas et al [<xref ref-type="bibr" rid="ref37">37</xref>]</td>
                <td>Virtual Reality Museum</td>
                <td>Cognitive training game</td>
                <td>Designed</td>
                <td>VR headset</td>
                <td>Supervised</td>
                <td>90</td>
                <td>2</td>
                <td>21</td>
              </tr>
              <tr valign="top">
                <td>Fiatarone Singh et al [<xref ref-type="bibr" rid="ref38">38</xref>]</td>
                <td>COGPACK</td>
                <td>Cognitive training game</td>
                <td>Designed</td>
                <td>PC</td>
                <td>Supervised</td>
                <td>75</td>
                <td>2</td>
                <td>25</td>
              </tr>
              <tr valign="top">
                <td>Amjad et al [<xref ref-type="bibr" rid="ref39">39</xref>]</td>
                <td>Body and Brain Exercises</td>
                <td>Cognitive training game</td>
                <td>Purpose-shifted</td>
                <td>Xbox console and Kinect</td>
                <td>Supervised</td>
                <td>25 to 30</td>
                <td>5</td>
                <td>6</td>
              </tr>
              <tr valign="top">
                <td>Wiloth et al [<xref ref-type="bibr" rid="ref40">40</xref>]</td>
                <td>Physiomat</td>
                <td>Exergame</td>
                <td>Designed</td>
                <td>Balance broad and screen</td>
                <td>Supervised</td>
                <td>90</td>
                <td>2</td>
                <td>10</td>
              </tr>
              <tr valign="top">
                <td>Van Santen et al [<xref ref-type="bibr" rid="ref41">41</xref>]</td>
                <td>NR</td>
                <td>Exergame</td>
                <td>Designed</td>
                <td>Stationary bicycle and screen</td>
                <td>Unsupervised</td>
                <td>NR</td>
                <td>5</td>
                <td>25</td>
              </tr>
              <tr valign="top">
                <td>Karssemeijer et al [<xref ref-type="bibr" rid="ref42">42</xref>]</td>
                <td>NR</td>
                <td>Exergame</td>
                <td>Purpose-shifted</td>
                <td>Stationary bicycle and screen</td>
                <td>Supervised</td>
                <td>30 to 50</td>
                <td>3</td>
                <td>12</td>
              </tr>
              <tr valign="top">
                <td>Liao et al [<xref ref-type="bibr" rid="ref43">43</xref>]</td>
                <td>Tano and LongGood</td>
                <td>Exergame</td>
                <td>Designed</td>
                <td>Kinect and VR headset</td>
                <td>Supervised</td>
                <td>60</td>
                <td>3</td>
                <td>12</td>
              </tr>
              <tr valign="top">
                <td>Flak et al [<xref ref-type="bibr" rid="ref44">44</xref>]</td>
                <td>Cogmed</td>
                <td>Cognitive training game</td>
                <td>Designed</td>
                <td>PC</td>
                <td>Unsupervised</td>
                <td>30 to 40</td>
                <td>5</td>
                <td>5</td>
              </tr>
              <tr valign="top">
                <td>Hyer et al [<xref ref-type="bibr" rid="ref45">45</xref>]</td>
                <td>Cogmed</td>
                <td>Cognitive training game</td>
                <td>Designed</td>
                <td>PC</td>
                <td>Both</td>
                <td>40</td>
                <td>7</td>
                <td>5 to 7</td>
              </tr>
              <tr valign="top">
                <td>Park and Park [<xref ref-type="bibr" rid="ref46">46</xref>]</td>
                <td>CoTras</td>
                <td>Cognitive training game</td>
                <td>Designed</td>
                <td>PC</td>
                <td>Supervised</td>
                <td>30</td>
                <td>3</td>
                <td>10</td>
              </tr>
            </tbody>
          </table>
          <table-wrap-foot>
            <fn id="table2fn1">
              <p><sup>a</sup>NR: not reported.</p>
            </fn>
            <fn id="table2fn2">
              <p><sup>b</sup>VR: virtual reality.</p>
            </fn>
          </table-wrap-foot>
        </table-wrap>
        <p>Half of the studies (8/16, 50%) delivered no or passive interventions to the comparison groups (eg, reading newspaper articles, surfing the internet, or watching a documentary program), whereas these groups received active interventions (eg, conventional exercises and other serious games) in 62% (10/16) of the studies (<xref ref-type="table" rid="table3">Table 3</xref>). A total of 12% (2/16) of the studies delivered both active and passive interventions as comparators. The active interventions had a duration ranging from 25 to 100 minutes. The active interventions were performed once to 7 times per week. The active comparator duration ranged from 5 to 25 weeks. The outcome of interest (ie, processing speed) was assessed using 11 different tools, with the Trail Making Test A being a frequently used tool in the included studies (7/16, 44%). The outcome of interest was measured after the intervention in all the included studies (16/16, 100%). In total, 44% (7/16) of the studies followed the participants after the interventions, and the follow-up period varied between 4 and 261 weeks. The number of participants who dropped out of the included studies ranged from 0 to 28.</p>
        <table-wrap position="float" id="table3">
          <label>Table 3</label>
          <caption>
            <p>Characteristics of the comparators and outcomes (N=16).</p>
          </caption>
          <table width="1000" cellpadding="5" cellspacing="0" border="1" rules="groups" frame="hsides">
            <col width="140"/>
            <col width="170"/>
            <col width="170"/>
            <col width="90"/>
            <col width="80"/>
            <col width="100"/>
            <col width="150"/>
            <col width="100"/>
            <thead>
              <tr valign="top">
                <td>Study</td>
                <td>Comparator</td>
                <td>Duration (minutes)</td>
                <td>Frequency (times per week)</td>
                <td>Period (weeks)</td>
                <td>Outcome measures</td>
                <td>Follow-up</td>
                <td>Attritions, N</td>
              </tr>
            </thead>
            <tbody>
              <tr valign="top">
                <td>Finn and McDonald [<xref ref-type="bibr" rid="ref31">31</xref>]</td>
                <td>Control</td>
                <td>N/A<sup>a</sup></td>
                <td>N/A</td>
                <td>N/A</td>
                <td>D-KEFS-NS<sup>b</sup></td>
                <td>After the intervention</td>
                <td>7</td>
              </tr>
              <tr valign="top">
                <td>Robert et al [<xref ref-type="bibr" rid="ref32">32</xref>]</td>
                <td>Control</td>
                <td>N/A</td>
                <td>N/A</td>
                <td>N/A</td>
                <td>TMT-A<sup>c</sup>, SCWT<sup>d</sup>, and WAIS-R-Dsy<sup>e</sup></td>
                <td>After the intervention; 12-week follow-up</td>
                <td>NR<sup>f</sup></td>
              </tr>
              <tr valign="top">
                <td>Savulich et al [<xref ref-type="bibr" rid="ref33">33</xref>]</td>
                <td>Control</td>
                <td>N/A</td>
                <td>N/A</td>
                <td>N/A</td>
                <td>CANTAB-CRT<sup>g</sup></td>
                <td>After the intervention</td>
                <td>0</td>
              </tr>
              <tr valign="top">
                <td>Valdes et al [<xref ref-type="bibr" rid="ref34">34</xref>]</td>
                <td>Control</td>
                <td>N/A</td>
                <td>N/A</td>
                <td>N/A</td>
                <td>UFOV<sup>h</sup></td>
                <td>After the intervention; 52-, 104-, 156-, and 261-week follow-up</td>
                <td>NR</td>
              </tr>
              <tr valign="top">
                <td>Yang and Kwak [<xref ref-type="bibr" rid="ref35">35</xref>]</td>
                <td>Control</td>
                <td>N/A</td>
                <td>N/A</td>
                <td>N/A</td>
                <td>GnG<sup>i</sup> and SCWT</td>
                <td>After the intervention</td>
                <td>0</td>
              </tr>
              <tr valign="top">
                <td>Thapa et al [<xref ref-type="bibr" rid="ref36">36</xref>]</td>
                <td>Control</td>
                <td>N/A</td>
                <td>N/A</td>
                <td>N/A</td>
                <td>TMT-A and SDST<sup>j</sup></td>
                <td>After the intervention</td>
                <td>2</td>
              </tr>
              <tr valign="top">
                <td>Tarnanas et al [<xref ref-type="bibr" rid="ref37">37</xref>]</td>
                <td>Control and conventional cognitive activities</td>
                <td>90</td>
                <td>2</td>
                <td>21</td>
                <td>SCWT</td>
                <td>After the intervention</td>
                <td>9</td>
              </tr>
              <tr valign="top">
                <td>Fiatarone Singh et al [<xref ref-type="bibr" rid="ref38">38</xref>]</td>
                <td>Control, conventional exercises+sham cognitive training, and serious games+conventional exercises</td>
                <td>Control: 75; conventional exercises+sham cognitive training: 100; serious games+conventional exercises: 60</td>
                <td>2</td>
                <td>25</td>
                <td>SDMT<sup>k</sup></td>
                <td>After the intervention; 74-week follow-up</td>
                <td>14</td>
              </tr>
              <tr valign="top">
                <td>Amjad et al [<xref ref-type="bibr" rid="ref39">39</xref>]</td>
                <td>Conventional exercises</td>
                <td>25 to 30</td>
                <td>5</td>
                <td>6</td>
                <td>TMT-A</td>
                <td>After the intervention</td>
                <td>6</td>
              </tr>
              <tr valign="top">
                <td>Wiloth et al [<xref ref-type="bibr" rid="ref40">40</xref>]</td>
                <td>Conventional exercises</td>
                <td>60</td>
                <td>2</td>
                <td>10</td>
                <td>TMT-A</td>
                <td>After the intervention; 12-week follow-up</td>
                <td>26</td>
              </tr>
              <tr valign="top">
                <td>Van Santen et al [<xref ref-type="bibr" rid="ref41">41</xref>]</td>
                <td>Conventional exercises</td>
                <td>N/A</td>
                <td>5</td>
                <td>25</td>
                <td>TMT-A</td>
                <td>Midintervention and after the intervention</td>
                <td>28</td>
              </tr>
              <tr valign="top">
                <td>Karssemeijer et al [<xref ref-type="bibr" rid="ref42">42</xref>]</td>
                <td>Conventional exercises (aerobic exercises); conventional exercises (relaxation and flexibility exercises)</td>
                <td>30 to 50</td>
                <td>3</td>
                <td>12</td>
                <td>TMT-A and SCWT</td>
                <td>Midintervention and after the intervention; 24-week follow-up</td>
                <td>23</td>
              </tr>
              <tr valign="top">
                <td>Liao et al [<xref ref-type="bibr" rid="ref43">43</xref>]</td>
                <td>Conventional exercises</td>
                <td>60</td>
                <td>3</td>
                <td>12</td>
                <td>SCWT</td>
                <td>After the intervention</td>
                <td>15</td>
              </tr>
              <tr valign="top">
                <td>Flak et al [<xref ref-type="bibr" rid="ref44">44</xref>]</td>
                <td>Nonadaptive serious game</td>
                <td>30 to 40</td>
                <td>5</td>
                <td>5</td>
                <td>D-KEFS-CWIT1<sup>l</sup> and D-KEFS-CWIT2<sup>m</sup></td>
                <td>After the intervention; 4- and 16-week follow-up</td>
                <td>17</td>
              </tr>
              <tr valign="top">
                <td>Hyer et al [<xref ref-type="bibr" rid="ref45">45</xref>]</td>
                <td>Nonadaptive serious game</td>
                <td>40</td>
                <td>7</td>
                <td>5 to 7</td>
                <td>TMT-A</td>
                <td>After the intervention; 12-week follow-up</td>
                <td>9</td>
              </tr>
              <tr valign="top">
                <td>Park and Park [<xref ref-type="bibr" rid="ref46">46</xref>]</td>
                <td>Exergames</td>
                <td>30</td>
                <td>3</td>
                <td>10</td>
                <td>SCWT</td>
                <td>After the intervention</td>
                <td>0</td>
              </tr>
            </tbody>
          </table>
          <table-wrap-foot>
            <fn id="table3fn1">
              <p><sup>a</sup>N/A: not applicable.</p>
            </fn>
            <fn id="table3fn2">
              <p><sup>b</sup>D-KEFS-NS: Delis-Kaplan Executive Function System Test Battery-Number Sequencing.</p>
            </fn>
            <fn id="table3fn3">
              <p><sup>c</sup>TMT-A: Trail Making Test A.</p>
            </fn>
            <fn id="table3fn4">
              <p><sup>d</sup>SCWT: Stroop Color and Word Test.</p>
            </fn>
            <fn id="table3fn5">
              <p><sup>e</sup>WAIS-R-Dsy: Wechsler Adult Intelligence Scale-Revised-Digit Symbol.</p>
            </fn>
            <fn id="table3fn6">
              <p><sup>f</sup>NR: not reported.</p>
            </fn>
            <fn id="table3fn7">
              <p><sup>g</sup>CANTAB-CRT: Cambridge Neuropsychological Test Automated Battery-Choice Reaction Time.</p>
            </fn>
            <fn id="table3fn8">
              <p><sup>h</sup>UFOV: Useful Field of View test.</p>
            </fn>
            <fn id="table3fn9">
              <p><sup>i</sup>GnG: go-no go.</p>
            </fn>
            <fn id="table3fn10">
              <p><sup>j</sup>SDST: Symbol Digit Substitution Test.</p>
            </fn>
            <fn id="table3fn11">
              <p><sup>k</sup>SDMT: Symbol Digit Modalities Test.</p>
            </fn>
            <fn id="table3fn12">
              <p><sup>l</sup>D-KEFS-CWIT1: Delis-Kaplan Executive Function System Color-Word Interference Test 1.</p>
            </fn>
            <fn id="table3fn13">
              <p><sup>m</sup>D-KEFS-CWIT2: Delis-Kaplan Executive Function System Color-Word Interference Test 2.</p>
            </fn>
          </table-wrap-foot>
        </table-wrap>
      </sec>
      <sec>
        <title>Results of Risk of Bias Appraisal</title>
        <p>As shown in <xref rid="figure2" ref-type="fig">Figure 2</xref>, a total of 31% (5/16) of the studies were judged to have a low risk of bias in the “randomization process” domain. With regard to the “deviations from the intended interventions” domain, there was a low risk of bias in 75% (12/16) of the studies. The risk of bias because of missing outcome data was low in 81% (13/16) of the studies. All the included studies (16/16, 100%) were judged to have a low risk of bias in the “measuring the outcome” domain. In half of the included studies (8/16, 50%), the risk of bias was rated as low in the “selection of the reported results” domain. According to these judgments, only 19% (3/16) of the studies were judged to have a low risk of bias in the last domain (ie, overall bias). Reviewers’ judgments about each “risk of bias” domain for each included study are presented in <xref ref-type="supplementary-material" rid="app4">Multimedia Appendix 4</xref> [<xref ref-type="bibr" rid="ref31">31</xref>-<xref ref-type="bibr" rid="ref46">46</xref>].</p>
        <fig id="figure2" position="float">
          <label>Figure 2</label>
          <caption>
            <p>Review authors’ judgments about each “risk of bias” domain.</p>
          </caption>
          <graphic xlink:href="games_v10i3e36754_fig2.png" alt-version="no" mimetype="image" position="float" xlink:type="simple"/>
        </fig>
      </sec>
      <sec>
        <title>Results of the Studies</title>
        <sec>
          <title>Serious Games Versus No or Passive Interventions</title>
          <p>The effect of serious games was compared with that of control (no or passive interventions) in 50% (8/16) of the studies [<xref ref-type="bibr" rid="ref31">31</xref>-<xref ref-type="bibr" rid="ref38">38</xref>]. Passive interventions are those that do not have a known effect on the measured outcome, such as reading newspaper articles, surfing the internet, and watching a documentary program. In 50% (4/8) of these studies [<xref ref-type="bibr" rid="ref32">32</xref>,<xref ref-type="bibr" rid="ref33">33</xref>,<xref ref-type="bibr" rid="ref35">35</xref>,<xref ref-type="bibr" rid="ref36">36</xref>], more than one outcome measure was used to assess processing speed. Therefore, we included the results of all these measures in the meta-analysis to form 14 comparisons. As shown in <xref rid="figure3" ref-type="fig">Figure 3</xref> [<xref ref-type="bibr" rid="ref31">31</xref>-<xref ref-type="bibr" rid="ref38">38</xref>], there was no statistically significant difference (<italic>P</italic>=.77) in processing speed between serious games and the control groups (SMD: −0.07, 95% CI −0.54 to 0.40). The statistical heterogeneity of the evidence was considerable (<italic>P</italic>&#60;.001; <italic>I</italic><sup>2</sup>=89%). The quality of the evidence was very low as it was downgraded by 6 levels owing to a high risk of bias, heterogeneity, and imprecision (<xref ref-type="supplementary-material" rid="app5">Multimedia Appendix 5</xref>).</p>
          <p>The SMDs of 2 comparisons seem to be outliers (−1.24 [<xref ref-type="bibr" rid="ref34">34</xref>] and 1.98 [<xref ref-type="bibr" rid="ref36">36</xref>]), although the characteristics of the studies in these comparisons were comparable with those of other studies in this meta-analysis. For this reason, we ran a sensitivity analysis to assess whether removing these outliers influenced the overall effect size and heterogeneity level. The sensitivity analysis showed that the difference in processing speed between the groups remained insignificant (<italic>P</italic>=.32), but the heterogeneity substantially decreased from 89% to 49%.</p>
          <fig id="figure3" position="float">
            <label>Figure 3</label>
            <caption>
              <p>Forest plot of 8 studies (14 comparisons) comparing the effect of serious games on processing speed with that of control [<xref ref-type="bibr" rid="ref31">31</xref>-<xref ref-type="bibr" rid="ref38">38</xref>].</p>
            </caption>
            <graphic xlink:href="games_v10i3e36754_fig3.png" alt-version="no" mimetype="image" position="float" xlink:type="simple"/>
          </fig>
        </sec>
        <sec>
          <title>Serious Games Versus Conventional Exercises</title>
          <p>The effect of serious games was compared with that of conventional exercises in 38% (6/16) of the studies [<xref ref-type="bibr" rid="ref38">38</xref>-<xref ref-type="bibr" rid="ref43">43</xref>]. Of these 6 studies, 1 (17%) compared serious games with 2 different conventional exercises (aerobic exercises and relaxation and flexibility exercises) and measured processing speed using 2 different tools [<xref ref-type="bibr" rid="ref42">42</xref>]. Therefore, we included the results of all these comparisons and measures in the meta-analysis to form 11 comparisons (<xref rid="figure4" ref-type="fig">Figure 4</xref> [<xref ref-type="bibr" rid="ref38">38</xref>-<xref ref-type="bibr" rid="ref43">43</xref>]). The meta-analysis showed no statistically significant difference (<italic>P</italic>=.58) in processing speed between the serious game and conventional exercise groups (SMD: −0.07, 95% CI −0.34 to 0.19). The statistical heterogeneity of the evidence was moderate (<italic>P</italic>&#60;.001; <italic>I</italic><sup>2</sup>=58%). The quality of the evidence was very low as it was downgraded by 6 levels owing to a high risk of bias, heterogeneity, and imprecision (<xref ref-type="supplementary-material" rid="app5">Multimedia Appendix 5</xref>).</p>
          <p>Two types of serious games were used in this comparison (ie, serious games vs conventional exercises): cognitive training games and exergames. We conducted a subgroup analysis to investigate whether cognitive training games and exergames had a different effect on processing speed (<xref rid="figure5" ref-type="fig">Figure 5</xref> [<xref ref-type="bibr" rid="ref38">38</xref>-<xref ref-type="bibr" rid="ref43">43</xref>]). The subgroup analysis of 12% (2/16) of the studies showed no statistically significant difference (<italic>P</italic>=.26) in processing speed between the cognitive training game group and the conventional exercise group (SMD: −0.37, 95% CI −1.00 to 0.27). The statistical heterogeneity of the evidence was moderate (<italic>P</italic>=.14; <italic>I</italic><sup>2</sup>=53%). The quality of the evidence was very low as it was downgraded by 4 levels owing to a high risk of bias, heterogeneity, and imprecision (<xref ref-type="supplementary-material" rid="app5">Multimedia Appendix 5</xref>). Furthermore, the subgroup analysis of 25% (4/16) of the studies (9 comparisons) showed no statistically significant difference (<italic>P</italic>=.88) in processing speed between the exergame group and the conventional exercise group (SMD: −0.02, 95% CI −0.31 to 0.27). The statistical heterogeneity of the evidence was substantial (<italic>P</italic>&#60;.001; <italic>I</italic><sup>2</sup>=72%). The quality of the evidence was very low as it was downgraded by 6 levels owing to a high risk of bias, heterogeneity, and imprecision (<xref ref-type="supplementary-material" rid="app5">Multimedia Appendix 5</xref>).</p>
          <fig id="figure4" position="float">
            <label>Figure 4</label>
            <caption>
              <p>Forest plot of 6 studies (11 comparisons) comparing the effect of serious games on processing speed with that of conventional exercises [<xref ref-type="bibr" rid="ref38">38</xref>-<xref ref-type="bibr" rid="ref43">43</xref>].</p>
            </caption>
            <graphic xlink:href="games_v10i3e36754_fig4.png" alt-version="no" mimetype="image" position="float" xlink:type="simple"/>
          </fig>
          <fig id="figure5" position="float">
            <label>Figure 5</label>
            <caption>
              <p>Forest plot of 6 studies (11 comparisons) comparing the effect of cognitive training games and exergames on processing speed with that of conventional exercises [<xref ref-type="bibr" rid="ref38">38</xref>-<xref ref-type="bibr" rid="ref43">43</xref>].</p>
            </caption>
            <graphic xlink:href="games_v10i3e36754_fig5.png" alt-version="no" mimetype="image" position="float" xlink:type="simple"/>
          </fig>
        </sec>
        <sec>
          <title>Serious Games Versus Other Serious Games</title>
          <p>In total, 19% (3/16) of the studies assessed the effect of serious games on processing speed in comparison with that of other serious games [<xref ref-type="bibr" rid="ref44">44</xref>-<xref ref-type="bibr" rid="ref46">46</xref>]. The first study (1/3, 33%) compared the effect of a cognitive training game with that of exergames and found no statistically significant difference (<italic>P</italic>=.76) in processing speed between the groups [<xref ref-type="bibr" rid="ref46">46</xref>]. The remaining 67% (2/3) of the studies compared the effect of cognitive training games that adjust the level of difficulty of the tasks based on an individual’s mastery in each level (ie, adaptive games) with that of the same games but without adjustment of the level of difficulty of the tasks (ie, nonadaptive games) [<xref ref-type="bibr" rid="ref44">44</xref>,<xref ref-type="bibr" rid="ref45">45</xref>]. Of the 2 studies, 1 (50%) showed no statistically significant difference in processing speed between the groups as measured by the Delis-Kaplan Executive Function System Color-Word Interference Test 1 (<italic>P</italic>=.91) and Delis-Kaplan Executive Function System Color-Word Interference Test 2 (<italic>P</italic>=.51) [<xref ref-type="bibr" rid="ref44">44</xref>]. The remaining study (1/2, 50%) did not report the findings related to the outcome measure Trail Making Test A [<xref ref-type="bibr" rid="ref45">45</xref>]. The first author of that study was contacted to obtain these findings, but he has not replied.</p>
        </sec>
      </sec>
    </sec>
    <sec sec-type="discussion">
      <title>Discussion</title>
      <sec>
        <title>Principal Findings</title>
        <p>This study compiled evidence regarding the effectiveness of serious games in improving processing speed among older adults with cognitive impairment. Our review revealed that serious games are as effective as no or passive interventions and conventional exercises in improving processing speed and that there is no difference between cognitive training games and exergames when compared with conventional exercises. The nonsuperior effect of serious games over no or passive interventions and conventional exercises may have been due to the following reasons: (1) serious games in the included studies targeted cognitive abilities in general rather than processing speed specifically and (2) the sample size in most of the included studies (10/16, 62%) was small (&#60;100).</p>
        <p>Our findings are consistent with findings of a previous review that showed no statistically significant difference in processing speed between the cognitive training game group and the passive or active intervention group among older adults with MCI or dementia [<xref ref-type="bibr" rid="ref17">17</xref>]. However, our findings are not consistent with findings of previous reviews [<xref ref-type="bibr" rid="ref16">16</xref>,<xref ref-type="bibr" rid="ref18">18</xref>-<xref ref-type="bibr" rid="ref20">20</xref>]. Specifically, 4 reviews showed that cognitive training games [<xref ref-type="bibr" rid="ref16">16</xref>,<xref ref-type="bibr" rid="ref19">19</xref>,<xref ref-type="bibr" rid="ref20">20</xref>] and exergames [<xref ref-type="bibr" rid="ref18">18</xref>] are more effective than other interventions (passive or active) in improving processing speed among healthy older adults. This inconsistency may be attributed to the fact that (1) all these reviews focused on older adults without cognitive impairment only, whereas our review focused on older adults with cognitive impairment [<xref ref-type="bibr" rid="ref16">16</xref>,<xref ref-type="bibr" rid="ref18">18</xref>-<xref ref-type="bibr" rid="ref20">20</xref>]; (2) they included quasi-experiments and pilot RCTs [<xref ref-type="bibr" rid="ref18">18</xref>,<xref ref-type="bibr" rid="ref19">19</xref>]; and (3) they did not compare the effect of serious games with that of a specific comparator (eg, no intervention, conventional exercises, or conventional cognitive activities) [<xref ref-type="bibr" rid="ref16">16</xref>,<xref ref-type="bibr" rid="ref18">18</xref>-<xref ref-type="bibr" rid="ref20">20</xref>].</p>
      </sec>
      <sec>
        <title>Strengths and Limitations</title>
        <sec>
          <title>Strengths</title>
          <p>This study is the only one of the aforementioned reviews [<xref ref-type="bibr" rid="ref16">16</xref>-<xref ref-type="bibr" rid="ref20">20</xref>] that compared both serious games and their types with a specific comparator (ie, no intervention and conventional exercises) and used the GRADE approach to assess the quality of the evidence that resulted from the meta-analyses, thereby enabling the reader to draw more accurate conclusions. Given that we included only RCTs, which are the most rigorous research method for studying cause-effect relationships [<xref ref-type="bibr" rid="ref47">47</xref>], our findings are more likely to be reliable than findings generated from reviews that included other study designs such as pilot RCTs and quasi-experiments.</p>
          <p>The risk of publication bias in this review was minimal given that we sought to identify as many relevant studies as possible through (1) searching the most popular databases in the IT and health fields and gray literature databases, (2) conducting backward and forward reference list checking, and (3) using a well-developed search query. The risk of selection bias in this review was not a concern as the study selection, data extraction, risk of bias assessment, and quality of evidence appraisal were conducted by 2 reviewers independently.</p>
        </sec>
        <sec>
          <title>Limitations</title>
          <p>This review focused on the effectiveness of digital serious games in improving processing speed among older adults with cognitive impairment. Hence, this review cannot comment on the effectiveness (1) of nondigital serious games or those used for nontherapeutic purposes (eg, diagnosis), (2) of serious games in improving other cognitive abilities (eg, attention, learning, and memory), and (3) of serious games among other age groups or those without cognitive impairment.</p>
          <p>The effect size estimated for each meta-analyzed study was likely overestimated or underestimated as we used postintervention data rather than the pre-post intervention change data to calculate it. We used postintervention data as most studies (12/16, 75%) did not report the mean and SD for pre-post intervention change in processing speed for each group, and the difference in processing speed between groups at baseline was not statistically significant in all studies.</p>
          <p>This review focused only on the short-term effect of serious games by pooling only postintervention data rather than follow-up data given that the follow-up period was not consistent among the 44% (7/16) of studies that reported follow-up data. As a result, we are unable to speculate on the long-term impact of serious games on processing speed. Given that this review did not include research published before 2010, studies written in a language other than English, quasi-experiments, or pilot RCTs, it is likely that this review missed some relevant studies.</p>
        </sec>
      </sec>
      <sec>
        <title>Practical and Research Implications</title>
        <sec>
          <title>Practical Implications</title>
          <p>The findings of this review should be cautiously interpreted for the following reasons: (1) the quality of the evidence from all meta-analyses was very low mainly because of high risk of bias, high heterogeneity, and imprecision of the estimated total effect sizes; (2) the number of studies included in some meta-analyses was small; and (3) the sample sizes in many meta-analyzed studies were small. Consequently, until more robust evidence is available, serious games should be offered or used as a supplement rather than an alternative intervention targeting processing speed.</p>
          <p>None of the included studies used smartphones as a platform for serious games. Smartphones are more appealing than other platforms as they are less expensive, more accessible, and more pervasive than computers and gaming consoles. In 2021, the global number of mobile devices and users was estimated to be approximately 15 billion and 7.1 billion, respectively, with these statistics likely to climb dramatically by 2025 [<xref ref-type="bibr" rid="ref48">48</xref>]. Thus, we recommend that gaming companies develop serious games that can be played via smartphones. None of the serious games in the included studies were designed to target processing speed. Therefore, there is an urgent need to develop serious games that specifically target processing speed.</p>
        </sec>
        <sec>
          <title>Research Implications</title>
          <p>Although this review addressed the research gap related to the short-term effect of serious games on processing speed among older adults with cognitive impairment, the following research gaps need further reviews to be bridged: (1) the long-term effect of serious games, (2) the effect of serious games on other cognitive abilities (eg, attention and visuospatial skills) and other disorders (eg, attention-deficit/hyperactivity disorder, autism, and motor disabilities), and (3) the effect of serious games among people from different age groups with or without cognitive impairment.</p>
          <p>As mentioned earlier, most studies in this review did not report the mean and SD for pre-post intervention change in processing speed. Researchers should report such information in their future publications to enable reviewers to calculate a more accurate effect size for each study. According to a previous review [<xref ref-type="bibr" rid="ref18">18</xref>], there have been many studies conducted to assess the effect of exergames on processing speed among healthy older adults. However, only 25% (4/16) of the studies in this review investigated the effect of exergames on processing speed among older adults with cognitive impairment. Further trials are needed to address the aforementioned research gap.</p>
          <p>In this review, only 6% (1/16) of the trials compared serious games with conventional cognitive training, and only 12% (2/16) compared adaptive serious games with nonadaptive serious games. We urge researchers to examine the aforementioned comparisons to reach more definitive conclusions. None of the included studies investigated the effect of serious games that specifically target processing speed rather than cognitive abilities in general. Future studies should use serious games that specifically target processing speed to examine their effect.</p>
          <p>The overall risk of bias was low in only 19% (3/16) of the included trials as the remaining studies had issues mainly in the randomization process or selection of the reported results (ie, unpublished protocol or analysis plan). Future trials should improve their quality by minimizing such bias. To this end, they should be conducted and reported according to recommended guidelines or tools such as the Risk of Bias 2 [<xref ref-type="bibr" rid="ref27">27</xref>], and they should have a large sample size that is enough to obtain the desired statistical power. As most of the included studies (14/16, 88%) were conducted in high-income countries, the generalizability of the findings of this review to lower-income countries may be restricted owing to the diversity of their cultures and socioeconomic conditions. Thus, more trials should be conducted in lower-income countries.</p>
        </sec>
      </sec>
      <sec>
        <title>Conclusions</title>
        <p>Serious games did not have a superior effect on processing speed among older adults with cognitive impairment in comparison with no or passive interventions and conventional exercises. However, this finding should be cautiously interpreted for the following reasons: (1) the quality of the evidence from all meta-analyses was very low mainly because of high risk of bias, high heterogeneity, and imprecision of the estimated total effect sizes; (2) the number of studies included in some meta-analyses was small; and (3) the sample sizes in many meta-analyzed studies were small. Therefore, until more robust evidence is available, serious games should be offered or used as a supplement rather than as an alternative intervention targeting processing speed. Future reviews should investigate the long-term impact of serious games on other cognitive abilities and disorders among people from different age groups with or without cognitive impairment. Further trials should be undertaken to investigate the effect of serious games that specifically target processing speed rather than cognitive abilities in general.</p>
      </sec>
    </sec>
  </body>
  <back>
    <app-group>
      <supplementary-material id="app1">
        <label>Multimedia Appendix 1</label>
        <p>PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) checklist.</p>
        <media xlink:href="games_v10i3e36754_app1.docx" xlink:title="DOCX File , 26 KB"/>
      </supplementary-material>
      <supplementary-material id="app2">
        <label>Multimedia Appendix 2</label>
        <p>Search strategy.</p>
        <media xlink:href="games_v10i3e36754_app2.docx" xlink:title="DOCX File , 30 KB"/>
      </supplementary-material>
      <supplementary-material id="app3">
        <label>Multimedia Appendix 3</label>
        <p>Data extraction form.</p>
        <media xlink:href="games_v10i3e36754_app3.docx" xlink:title="DOCX File , 25 KB"/>
      </supplementary-material>
      <supplementary-material id="app4">
        <label>Multimedia Appendix 4</label>
        <p>Reviewers’ judgments about each “risk of bias” domain for each included study.</p>
        <media xlink:href="games_v10i3e36754_app4.docx" xlink:title="DOCX File , 108 KB"/>
      </supplementary-material>
      <supplementary-material id="app5">
        <label>Multimedia Appendix 5</label>
        <p>Grading of Recommendations Assessment, Development, and Evaluation profile for comparison of serious games with control and conventional exercises regarding processing speed.</p>
        <media xlink:href="games_v10i3e36754_app5.doc" xlink:title="DOC File , 18 KB"/>
      </supplementary-material>
    </app-group>
    <glossary>
      <title>Abbreviations</title>
      <def-list>
        <def-item>
          <term id="abb1">AD</term>
          <def>
            <p>Alzheimer disease</p>
          </def>
        </def-item>
        <def-item>
          <term id="abb2">GRADE</term>
          <def>
            <p>Grading of Recommendations Assessment, Development, and Evaluation</p>
          </def>
        </def-item>
        <def-item>
          <term id="abb3">MCI</term>
          <def>
            <p>mild cognitive impairment</p>
          </def>
        </def-item>
        <def-item>
          <term id="abb4">PRISMA</term>
          <def>
            <p>Preferred Reporting Items for Systematic Reviews and Meta-Analyses</p>
          </def>
        </def-item>
        <def-item>
          <term id="abb5">RCT</term>
          <def>
            <p>randomized controlled trial</p>
          </def>
        </def-item>
        <def-item>
          <term id="abb6">SMD</term>
          <def>
            <p>standardized mean difference</p>
          </def>
        </def-item>
      </def-list>
    </glossary>
    <fn-group>
      <fn fn-type="conflict">
        <p>None declared.</p>
      </fn>
    </fn-group>
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