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<front>
<journal-meta>
<journal-id journal-id-type="publisher-id">Front. Neurosci.</journal-id>
<journal-title>Frontiers in Neuroscience</journal-title>
<abbrev-journal-title abbrev-type="pubmed">Front. Neurosci.</abbrev-journal-title>
<issn pub-type="epub">1662-453X</issn>
<publisher>
<publisher-name>Frontiers Media S.A.</publisher-name>
</publisher>
</journal-meta>
<article-meta>
<article-id pub-id-type="doi">10.3389/fnins.2023.1221990</article-id>
<article-categories>
<subj-group subj-group-type="heading">
<subject>Neuroscience</subject>
<subj-group>
<subject>Review</subject>
</subj-group>
</subj-group>
</article-categories>
<title-group>
<article-title>Association between sedentary behavior and risk of cognitive decline or mild cognitive impairment among the elderly: a systematic review and meta-analysis</article-title>
</title-group>
<contrib-group>
<contrib contrib-type="author">
<name><surname>Cai</surname> <given-names>Xiao-ye</given-names></name>
<xref ref-type="aff" rid="aff1"><sup>1</sup></xref>
<uri xlink:href="http://loop.frontiersin.org/people/2311522/overview"/>
</contrib>
<contrib contrib-type="author">
<name><surname>Qian</surname> <given-names>Guo-ping</given-names></name>
<xref ref-type="aff" rid="aff2"><sup>2</sup></xref>
<uri xlink:href="http://loop.frontiersin.org/people/1907145/overview"/>
</contrib>
<contrib contrib-type="author">
<name><surname>Wang</surname> <given-names>Feng</given-names></name>
<xref ref-type="aff" rid="aff3"><sup>3</sup></xref>
</contrib>
<contrib contrib-type="author">
<name><surname>Zhang</surname> <given-names>Ming-yang</given-names></name>
<xref ref-type="aff" rid="aff2"><sup>2</sup></xref>
<xref ref-type="aff" rid="aff4"><sup>4</sup></xref>
<uri xlink:href="http://loop.frontiersin.org/people/1967336/overview"/>
</contrib>
<contrib contrib-type="author">
<name><surname>Da</surname> <given-names>Ying-juan</given-names></name>
<xref ref-type="aff" rid="aff1"><sup>1</sup></xref>
</contrib>
<contrib contrib-type="author" corresp="yes">
<name><surname>Liang</surname> <given-names>Jing-hong</given-names></name>
<xref ref-type="aff" rid="aff5"><sup>5</sup></xref>
<xref ref-type="corresp" rid="c001"><sup>&#x0002A;</sup></xref>
<uri xlink:href="http://loop.frontiersin.org/people/1321161/overview"/>
</contrib>
</contrib-group>
<aff id="aff1"><sup>1</sup><institution>Department of Physical Education, Shanghai Normal University Tianhua College</institution>, <addr-line>Shanghai</addr-line>, <country>China</country></aff>
<aff id="aff2"><sup>2</sup><institution>Faculty of Physical Culture, Gdansk University of Physical Education and Sport</institution>, <addr-line>Gda&#x00144;sk</addr-line>, <country>Poland</country></aff>
<aff id="aff3"><sup>3</sup><institution>Department of Physical Education, Shanghai Ocean University</institution>, <addr-line>Shanghai</addr-line>, <country>China</country></aff>
<aff id="aff4"><sup>4</sup><institution>Department of Physical Education, Chengdu Sport University</institution>, <addr-line>Chengdu</addr-line>, <country>China</country></aff>
<aff id="aff5"><sup>5</sup><institution>Department of Maternal and Child Health, School of Public Health, Sun Yat-sen University</institution>, <addr-line>Guangzhou</addr-line>, <country>China</country></aff>
<author-notes>
<fn fn-type="edited-by"><p>Edited by: Chong Tian, Huazhong University of Science and Technology, China</p></fn>
<fn fn-type="edited-by"><p>Reviewed by: Shouli Wang, Shanghai Jiao Tong University, China; Kun Huang, Central South University, China; Xia Zeng, Guangdong Pharmaceutical University, China</p></fn>
<corresp id="c001">&#x0002A;Correspondence: Jing-hong Liang <email>liangjh78&#x00040;mail2.sysu.edu.cn</email></corresp>
</author-notes>
<pub-date pub-type="epub">
<day>04</day>
<month>08</month>
<year>2023</year>
</pub-date>
<pub-date pub-type="collection">
<year>2023</year>
</pub-date>
<volume>17</volume>
<elocation-id>1221990</elocation-id>
<history>
<date date-type="received">
<day>13</day>
<month>05</month>
<year>2023</year>
</date>
<date date-type="accepted">
<day>13</day>
<month>07</month>
<year>2023</year>
</date>
</history>
<permissions>
<copyright-statement>Copyright &#x000A9; 2023 Cai, Qian, Wang, Zhang, Da and Liang.</copyright-statement>
<copyright-year>2023</copyright-year>
<copyright-holder>Cai, Qian, Wang, Zhang, Da and Liang</copyright-holder>
<license xlink:href="http://creativecommons.org/licenses/by/4.0/"><p>This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.</p></license> </permissions>
<abstract>
<sec>
<title>Background</title>
<p>Existing evidence on the association between sedentary behavior (SB) and cognitive function remains inconclusive. Therefore, this study investigated the association between SB and the risk of cognitive decline (CD) or mild cognitive impairment (MCI) in the elderly.</p></sec>
<sec>
<title>Methods</title>
<p>A comprehensive search was independently conducted by two researchers (XC and GQ) in seven electronic databases, including Medline (via PubMed), China Biology Medicine, Embase, Web of Science, China National Knowledge Infrastructure, Wanfang database, and VIP database for Chinese technical periodicals, covering studies published from the inception of database to June 2023. Studies that investigated the relationship between SB and the risk of CD or MCI in the elderly were included. The quality of the literature was assessed using the Newcastle&#x02013;Ottawa Scale (NOS) and the Agency for Healthcare Research and Quality (AHRQ) assessment tools. The combined effect size analysis, subgroup analysis, and publication bias assessment were performed using STATA 14.0.</p></sec>
<sec>
<title>Results</title>
<p>A total of 13 cross-sectional and 6 cohort studies involving 81,791 individuals were included, comprising 17 high-quality studies and 2 medium-quality studies. We found that SB was significantly associated with an increased risk of CD [odds ratio (OR) = 1.69, 95% confidence intervals (CI): 1.47&#x02013;1.94] or MCI (OR = 1.34, 95% CI: 1.14&#x02013;1.56) among the elderly. Subgroup analysis stratified according to comorbidity, lifestyle, family structure, publication year, and region showed statistical differences between groups, and the consistency of the results revealed the sources of the heterogeneity.</p></sec>
<sec>
<title>Conclusion</title>
<p>This meta-analysis showed that SB is positively associated with the risk of CD or MCI in the elderly, providing a higher level of evidence for the promotion of healthy behaviors by clinicians and health policymakers. Due to the number and quality of the included articles, more high-quality longitudinal studies are needed to further confirm our findings.</p></sec></abstract>
<kwd-group>
<kwd>sedentary behavior</kwd>
<kwd>cognitive decline</kwd>
<kwd>mild cognitive impairment</kwd>
<kwd>elderly</kwd>
<kwd>meta-analysis</kwd>
</kwd-group>
<counts>
<fig-count count="3"/>
<table-count count="2"/>
<equation-count count="0"/>
<ref-count count="57"/>
<page-count count="13"/>
<word-count count="8474"/>
</counts>
<custom-meta-wrap>
<custom-meta>
<meta-name>section-at-acceptance</meta-name>
<meta-value>Translational Neuroscience</meta-value>
</custom-meta>
</custom-meta-wrap>
</article-meta>
</front>
<body>
<sec sec-type="intro" id="s1">
<title>Introduction</title>
<p>Cognitive decline (CD) refers to the measurable deterioration observed in various domains of cognitive function, including memory, language, and reasoning (Chun et al., <xref ref-type="bibr" rid="B5">2021</xref>). It represents the preclinical stage of the Alzheimer&#x00027;s disease (AD) continuum, with &#x0007E;7% of CD per year progressing to mild cognitive impairment (MCI) (Mazzeo et al., <xref ref-type="bibr" rid="B36">2019</xref>). MCI is a state of cognitive impairment between normal aging and dementia (Albert et al., <xref ref-type="bibr" rid="B1">2011</xref>). MCI refers to significant memory deterioration and mild impairment in other domains of cognitive function that do not yet meet the diagnostic criteria for dementia (Langa and Levine, <xref ref-type="bibr" rid="B27">2014</xref>). The incidence of MCI is 20.8%, and &#x0007E;10&#x02013;20% of MCI progresses to AD annually (Jia et al., <xref ref-type="bibr" rid="B20">2020</xref>). Cognitive impairment is irreversible, and there are no effective pharmacological or interventional treatments for the condition (Rojas-Fernandez and Cameron, <xref ref-type="bibr" rid="B45">2012</xref>; Yu et al., <xref ref-type="bibr" rid="B56">2023</xref>). Therefore, understanding the risk factors of CD and MCI could enhance the prevention of AD (Petersen et al., <xref ref-type="bibr" rid="B42">2018</xref>).</p>
<p>In 2017, the members of the Sedentary Behavior Research Network (SBRN) defined SB as all activities with &#x02264; 1.5 metabolic equivalents (METs) of energy expenditure, such as sitting or lying down (Tremblay et al., <xref ref-type="bibr" rid="B50">2017</xref>). SB is common in the elderly and is an independent risk factor for certain diseases (Keadle et al., <xref ref-type="bibr" rid="B22">2017</xref>). Numerous studies have shown that SB is associated with elevated risks of all-cause mortality, cardiovascular mortality, cancer mortality, and the incidence of type 2 diabetes in the elderly population (Bull et al., <xref ref-type="bibr" rid="B4">2020</xref>; Liang et al., <xref ref-type="bibr" rid="B32">2022</xref>). Recently, there has been growing interest in the relationship between SB and cognitive function (Poulin et al., <xref ref-type="bibr" rid="B44">2016</xref>), but issues that have been raised by previous studies remain to be resolved. First, the available evidence remains controversial. For instance, some studies have shown that SB is associated with lower cognitive function and is independently associated with a significantly higher risk of dementia (Falck et al., <xref ref-type="bibr" rid="B11">2017</xref>; Yan et al., <xref ref-type="bibr" rid="B55">2020</xref>). However, two other studies showed that there was no association between SB and cognitive function over time (Kesse-Guyot et al., <xref ref-type="bibr" rid="B24">2012</xref>; Hamer and Stamatakis, <xref ref-type="bibr" rid="B19">2014</xref>). Possible explanations for these differences are that these studies, published over a decade ago, were not appropriately designed, the 2-year follow-up may not have been sufficient to detect longitudinal changes, and SB was self-reported and less objective. Second, previous systematic reviews were based on qualitative studies that had limitations in terms of sample size, population diversity, and the inclusion of individuals with underlying medical conditions (Falck et al., <xref ref-type="bibr" rid="B11">2017</xref>). Thus, further research is needed to improve the quality of evidence and its applicability. Overall, differences in exposures, small sample sizes, short follow-up periods, self-reported SB measures, and uneven quality of review articles often lead to conflicting findings (Hamer and Stamatakis, <xref ref-type="bibr" rid="B19">2014</xref>; Falck et al., <xref ref-type="bibr" rid="B11">2017</xref>). As a result, there is a need to combine and summarize data on the relationship between SB and the risk of CD or MCI to obtain more robust evidence. Thus, we performed a systematic review and meta-analysis of relevant published studies to assess this relationship.</p>
</sec>
<sec sec-type="methods" id="s2">
<title>Methods</title>
<p>This meta-analysis was conducted following the guidelines of Meta-analysis of Observational Studies in Epidemiology (MOOSE) and the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) (Stroup et al., <xref ref-type="bibr" rid="B49">2000</xref>; Page et al., <xref ref-type="bibr" rid="B39">2021</xref>). Ethical approval was not required because the study was based on previously published articles. In addition, the authors had no conflicts of interest.</p>
<sec>
<title>Search strategies and study selection</title>
<p>The reviewed databases included Medline (via PubMed), China Biology Medicine, Embase, Web of Science, China National Knowledge Infrastructure, Wanfang database, and VIP database for Chinese technical periodicals. They were systematically searched to identify relevant articles published from inception to 11 June 2023. The search was performed using a combination of free words and theme words. Search strategies were developed using Boolean logical operators and truncates. The main search terms included &#x0201C;cognitive dysfunctions,&#x0201D; &#x0201C;mild cognitive impairment,&#x0201D; &#x0201C;cognitive decline,&#x0201D; &#x0201C;cognition,&#x0201D; &#x0201C;sedentary behavior,&#x0201D; &#x0201C;sedentary lifestyle,&#x0201D; &#x0201C;physical inactivity,&#x0201D; and &#x0201C;sedentary time&#x0201D; (see <xref ref-type="supplementary-material" rid="SM1">Supplementary material 1</xref> for detailed search strategies). Moreover, articles included in the literature of the relevant systematic review and meta-analysis studies were also searched. This was supplemented by a manual search of conference articles or gray literature to identify references cited in the included literature. When full text was not available, the authors&#x00027; or corresponding authors&#x00027; email addresses or other contact details were sought to request full-text access. Two researchers (XC and GQ) independently performed a comprehensive literature search and exported the identified articles to Endnote X9 software (Thompson ISI Research Soft, Philadelphia, USA). After eliminating duplicates manually and electronically with the software, initial screening was performed by reading the titles and abstracts of the articles to exclude irrelevant articles. Next, full-text screening of the articles was conducted, and articles that did not meet the inclusion criteria were removed. In case of discrepancies in the selection of the articles, a senior expert of the research group was consulted to reach a consensus.</p>
</sec>
<sec>
<title>Inclusion and exclusion criteria</title>
<p>Literature inclusion was based on the population, intervention, comparison, outcome, and study design (PICOS) principles of evidence-based medicine (Liberati et al., <xref ref-type="bibr" rid="B33">2009</xref>). The inclusion criteria were as follows: (1) Mean age or age range of the participants &#x02265; 60 years [The United Nations (UN) defines elderly individuals as those aged 60 years and above (United Nations, <xref ref-type="bibr" rid="B51">2019</xref>)] and CD or MCI patients with undiagnosed dementia. Diagnostic criteria were based on elements from the National Institute of Aging Alzheimer&#x00027;s Association (NIA-AA), the Diagnostic and Statistical Manual of Mental Disorders (DSM), and Petersen&#x00027;s criteria (Montine et al., <xref ref-type="bibr" rid="B37">2012</xref>; Battle, <xref ref-type="bibr" rid="B2">2013</xref>; Petersen et al., <xref ref-type="bibr" rid="B42">2018</xref>); (2) articles were cross-sectional, cohort, and case&#x02013;control studies, without language restrictions; (3) outcome indicators including CD or MCI, according to the Mini-Mental State Examination (MMSE), the scores ranged from 0 to 30. The boundary values of CD and MCI were divided according to educational level: illiteracy &#x02264; 17 points, primary school &#x02264; 20 points, and junior high school and above &#x02264; 24 points) (Folstein et al., <xref ref-type="bibr" rid="B13">1975</xref>); Montreal Cognitive Assessment (MoCA) (Dong et al., <xref ref-type="bibr" rid="B9">2012</xref>); and Ascertain Dementia 8 (AD 8) (Galvin et al., <xref ref-type="bibr" rid="B15">2005</xref>); and (4) the exposure indicator was SB or physical inactivity. The exclusion criteria were as follows: (1) randomized controlled trials, literature reviews, abstracts, repeatedly published literature, and animal studies literature; (2) studies with incomplete data on outcome indicators; (3) low-quality articles with flaws in the study design; and (4) articles that combined other interventions and did not adjust for confounding factors.</p>
</sec>
<sec>
<title>Data extraction and quality assessment</title>
<p>Two researchers (XC and GQ) extracted data from the included studies separately, and disagreements were resolved by consensus or consultation with a third researcher. Data extracted from the articles included the year of publication, type of study, follow-up period, region, age, sex ratio, sample size, exposure characteristics, and outcome indicators. In addition, when there were several studies in the same article, the data were extracted separately, and in the case of incomplete data, the authors were contacted to request the complete data. Quality assessment of the included studies was conducted using the Newcastle&#x02013;Ottawa Scale (NOS) and the Agency for Healthcare Research and Quality (AHRQ) (Rostom et al., <xref ref-type="bibr" rid="B46">2004</xref>; Stang, <xref ref-type="bibr" rid="B48">2010</xref>). Specifically, the quality of cohort and case&#x02013;control studies was assessed using the NOS scale, focusing on three main aspects: sample selection, comparability, and outcomes or exposure, with a total score of 9. A score of one point was assigned for each of the following criteria: consistency of the study with the exposure, selection of the control from the same population, adequate representation of the population, absence of pre-study occurrence of the disease under investigation, and objective ascertainment of exposure. One point each was deducted if the study involved two distinct groups, namely individuals with medical histories requiring further investigation, or recorded the exposure factors through self-reporting. Moreover, two points were assigned in cases of good comparability of studies and correction of important factors. In addition, three points were allocated in cases where outcomes were assessed, follow-up was appropriate, or exposure and response rates were assessed. Points were deducted for failure to mention response rates, missed visits, or short follow-up periods. Scores ranging from 0 to 3 were categorized as low quality, scores from 4 to 6 were considered moderate quality, and scores from 7 to 9 were classified as high quality. For cross-sectional studies, the AHRQ scale was used for quality assessment. It contained 11 items, with a response of &#x0201C;yes,&#x0201D; &#x0201C;no,&#x0201D; and &#x0201C;unclear.&#x0201D; A score ranging from 0 to 3 was classified as low quality, scores from 4 to 7 were considered moderate quality, and scores from 8 to 11 were categorized as high quality. Disagreements on the quality of the literature were resolved by consensus or consultation with another experienced researcher.</p>
</sec>
<sec>
<title>Statistical analyses</title>
<p>Meta-analysis was performed using STATA 14.0 software. The combined odds ratios (OR) and 95% confidence intervals (CI) were used to evaluate the relationship between SB and the risk of CD or MCI in the elderly, with a <italic>P</italic>- value of &#x02264; 0.05 representing statistically significant differences across the two groups. The existence of heterogeneity among studies was assessed using the <italic>I</italic><sup>2</sup> test. If the <italic>P</italic>-value is &#x0003E;0.1 and <italic>I</italic><sup>2</sup> &#x02264; 50%, indicating low heterogeneity among the studies, the fixed effects model was used for the analysis. On the other hand, if the <italic>P</italic>-value is &#x02264; 0.1 and <italic>I</italic><sup>2</sup> &#x0003E; 50%, indicating significant heterogeneity between studies, the random effects model was used for analysis. To address studies with a high level of heterogeneity, subgroup analysis was conducted by dividing the variables into two groups. The sources of heterogeneity were explored based on the following factors: the period of follow-up (&#x02265;3 vs. &#x0003C;3 years), region (developed countries vs. developing or undeveloped countries), sample size (&#x02265;1,000 vs. &#x0003C;1,000), year of publication (&#x02265;2017 vs. &#x0003C;2017), length of SB exposure (&#x02265;5 vs. &#x0003C;5 h/day), complications (yes vs. no), lifestyle (adjusted vs. unadjusted smoking, drinking, sleeping, various activity behaviors, and healthy eating), comorbidity (adjusted vs. unadjusted depression, anxiety, obesity, diabetes, stroke, hypertension, medications, medical history, and rheumatic disease), and family structure (adjusted vs. unadjusted marital status, residential status, and living alone). In addition, statistical significance was evaluated by testing for differences across the effect sizes of each subgroup using a 95% CI. Egger&#x00027;s test was used to evaluate publication bias in the included studies, and a <italic>P</italic>-value of &#x0003E;0.05 hypothetically indicated that there was no publication bias.</p>
</sec>
</sec>
<sec sec-type="results" id="s3">
<title>Results</title>
<sec>
<title>Literature selection</title>
<p>A total of 9,713 relevant articles were retrieved from each database, and 1,699 duplicate articles were removed. After the initial screening of titles and abstracts, 7,782 articles were excluded, and 232 were selected for full-text screening. Furthermore, 213 articles did not meet the criteria and were excluded. Finally, 19 articles (13 cross-sectional and six cohort studies) were included (Ferreira et al., <xref ref-type="bibr" rid="B12">2010</xref>; Dogra and Stathokostas, <xref ref-type="bibr" rid="B8">2012</xref>; Lee et al., <xref ref-type="bibr" rid="B29">2013</xref>; Gillum et al., <xref ref-type="bibr" rid="B17">2015</xref>; Lara et al., <xref ref-type="bibr" rid="B28">2016</xref>; Paulo et al., <xref ref-type="bibr" rid="B40">2016</xref>; Brunner et al., <xref ref-type="bibr" rid="B3">2017</xref>; Gomes et al., <xref ref-type="bibr" rid="B18">2017</xref>; Ku et al., <xref ref-type="bibr" rid="B26">2017a</xref>,<xref ref-type="bibr" rid="B25">b</xref>; Garc&#x000ED;a-Hermoso et al., <xref ref-type="bibr" rid="B16">2018</xref>; Nemoto et al., <xref ref-type="bibr" rid="B38">2018</xref>; Vancampfort et al., <xref ref-type="bibr" rid="B52">2018</xref>; Mart&#x000ED;nez-Sanguinetti et al., <xref ref-type="bibr" rid="B35">2019</xref>; Poblete-Valderrama et al., <xref ref-type="bibr" rid="B43">2019</xref>; Jung and Chung, <xref ref-type="bibr" rid="B21">2020</xref>; Cui et al., <xref ref-type="bibr" rid="B7">2021</xref>; Du et al., <xref ref-type="bibr" rid="B10">2022</xref>; Song and Park, <xref ref-type="bibr" rid="B47">2022</xref>). The flow chart illustrating the literature screening process is shown in <xref ref-type="fig" rid="F1">Figure 1</xref>.</p>
<fig id="F1" position="float">
<label>Figure 1</label>
<caption><p>Literature review flowchart. CBM, China biology medicine; CNKI, China national knowledge infrastructure; RCT, randomized controlled trial; VIP, VIP database for Chinese technical periodicals; WFDB, Wanfang database; WOS, Web of Science.</p></caption>
<graphic mimetype="image" mime-subtype="tiff" xlink:href="fnins-17-1221990-g0001.tif"/>
</fig>
</sec>
<sec>
<title>Baseline data of included literature</title>
<p>A total of 19 articles involving 81,791 subjects were included. The included articles originated from 29 countries. In total, 10 of the articles came from developing countries, accounting for 53%, including four articles from China. Articles from developed countries accounted for 47%, with Japan and South Korea each having two articles. Moreover, six of the included articles were cohort studies, with a mean follow-up period of 4.3 years, and the others were cross-sectional studies published between 2012 and 2022. In total, 17 studies reported the sample sizes of the exposure and control groups, and only six reported the proportion of men and women. The method used for cognitive function testing in 11 articles was MMSE, and the testing method in two articles was AD 8. Eight articles analyzed different gradients of sedentary duration or physical inactivity. The detailed basic characteristics of the included studies are shown in <xref ref-type="table" rid="T1">Table 1</xref>.</p>
<table-wrap position="float" id="T1">
<label>Table 1</label>
<caption><p>Characteristics of included studies.</p></caption> 
<table frame="box" rules="all">
<thead>
<tr style="background-color:&#x00023;919498;color:&#x00023;ffffff">
<th valign="top" align="left"><bold>Publications</bold></th>
<th valign="top" align="center"><bold>Region</bold></th>
<th valign="top" align="center"><bold>Study design</bold></th>
<th valign="top" align="center"><bold>Follow-up duration (year)</bold></th>
<th valign="top" align="center" colspan="2"><bold>Number of participants</bold></th>
<th valign="top" align="center" colspan="2"><bold>Proportion of female (%)</bold></th>
<th valign="top" align="center" colspan="2"><bold>Age (mean</bold>&#x000B1;<bold>SD)</bold></th>
<th valign="top" align="center"><bold>Exposure group</bold></th>
<th valign="top" align="center"><bold>Control group</bold></th>
<th valign="top" align="center"><bold>Outcomes</bold></th>
</tr>
</thead>
<tbody>
<tr style="background-color:&#x00023;919498;color:&#x00023;ffffff">
<td/>
<td/>
<td/>
<td/>
<td valign="top" align="center"><bold>EG</bold></td>
<td valign="top" align="center"><bold>CG</bold></td>
<td valign="top" align="center"><bold>EG</bold></td>
<td valign="top" align="center"><bold>CG</bold></td>
<td valign="top" align="center"><bold>EG</bold></td>
<td valign="top" align="center"><bold>CG</bold></td>
<td/>
<td/>
<td/>
</tr>
<tr>
<td valign="top" align="left">Ku et al. (<xref ref-type="bibr" rid="B26">2017a</xref>)</td>
<td valign="top" align="center">Taiwan, China</td>
<td valign="top" align="center">CS</td>
<td valign="top" align="center">2</td>
<td valign="top" align="center">133</td>
<td valign="top" align="center">86</td>
<td valign="top" align="center" colspan="2">NR</td>
<td valign="top" align="center" colspan="2">74.50 &#x000B1; 6.10</td>
<td valign="top" align="center">Medium ST 7&#x02013;10.99 h/day/High ST 11&#x0002B; h/day</td>
<td valign="top" align="center">Low ST &#x0003C; 7 h/day</td>
<td valign="top" align="center">CD (&#x02460;)</td>
</tr>
<tr>
<td valign="top" align="left">Ferreira et al. (<xref ref-type="bibr" rid="B12">2010</xref>)</td>
<td valign="top" align="center">Brazil</td>
<td valign="top" align="center">CS</td>
<td valign="top" align="center">3</td>
<td valign="top" align="center">628</td>
<td valign="top" align="center">232</td>
<td valign="top" align="center" colspan="2">NR</td>
<td valign="top" align="center" colspan="2">74.90 &#x000B1; 6.70</td>
<td valign="top" align="center">Not favorable behavior trend in PAL &#x0002B; MMSE &#x0003C; 24</td>
<td valign="top" align="center">Not favorable behavior trend in PAL &#x0002B; MMSE 24&#x0002B;</td>
<td valign="top" align="center">CD (&#x02461;)</td>
</tr>
<tr>
<td valign="top" align="left">Lee et al. (<xref ref-type="bibr" rid="B29">2013</xref>)</td>
<td valign="top" align="center">Japan</td>
<td valign="top" align="center">CS</td>
<td valign="top" align="center">8</td>
<td valign="top" align="center" colspan="2">550</td>
<td valign="top" align="center" colspan="2">47.40%</td>
<td valign="top" align="center" colspan="2">&#x02265;60</td>
<td valign="top" align="center">Second ST/third ST/highest ST &#x02264; 1.5 METs-per day (hours)</td>
<td valign="top" align="center">Lowest ST &#x02264; 1.5 METs-per day (hours)</td>
<td valign="top" align="center">CD (&#x02461;)</td>
</tr>
<tr>
<td valign="top" align="left">Song and Park (<xref ref-type="bibr" rid="B47">2022</xref>)</td>
<td valign="top" align="center">Korea</td>
<td valign="top" align="center">CS</td>
<td valign="top" align="center">6</td>
<td valign="top" align="center">400</td>
<td valign="top" align="center">450</td>
<td valign="top" align="center">49.20%</td>
<td valign="top" align="center">36.60%</td>
<td valign="top" align="center">71.45 &#x000B1; 5.32</td>
<td valign="top" align="center">71.16 &#x000B1; 4.77</td>
<td valign="top" align="center">Became inactive/remained inactive</td>
<td valign="top" align="center">Remained active</td>
<td valign="top" align="center">CD (&#x02461;)</td>
</tr>
<tr>
<td/>
<td/>
<td/>
<td/>
<td valign="top" align="center">660</td>
<td/>
<td valign="top" align="center">58.20%</td>
<td/>
<td valign="top" align="center">72.29 &#x000B1; 5.27</td>
<td/>
<td/>
<td/>
<td/>
</tr>
<tr>
<td valign="top" align="left">Gomes et al. (<xref ref-type="bibr" rid="B18">2017</xref>)</td>
<td valign="top" align="center">16 European countries</td>
<td valign="top" align="center">CSS</td>
<td valign="top" align="center">1</td>
<td valign="top" align="center">4,006</td>
<td valign="top" align="center">1,005</td>
<td valign="top" align="center" colspan="2">NR</td>
<td valign="top" align="center" colspan="2">67.80 &#x000B1; 8.90</td>
<td valign="top" align="center">Physical inactivity &#x0002B; very good memory</td>
<td valign="top" align="center">Physical inactivity &#x0002B; poor memory</td>
<td valign="top" align="center">CD (memory)</td>
</tr>
<tr>
<td valign="top" align="left">Brunner et al. (<xref ref-type="bibr" rid="B3">2017</xref>)</td>
<td valign="top" align="center">UK</td>
<td valign="top" align="center">CS</td>
<td valign="top" align="center">5</td>
<td valign="top" align="center">564</td>
<td valign="top" align="center">2,837</td>
<td valign="top" align="center" colspan="2">NR</td>
<td valign="top" align="center" colspan="2">&#x02265;60</td>
<td valign="top" align="center">Inactivity &#x0003C; 1 h/week moderate and &#x0003C; 1 h/week vigorous PA</td>
<td valign="top" align="center">Sufficiently active &#x02265; 2.5 h/week moderate or &#x02265;1 h/week vigorous PA</td>
<td valign="top" align="center">MCI (&#x02461;)</td>
</tr>
<tr>
<td valign="top" align="left">Ku et al. (<xref ref-type="bibr" rid="B25">2017b</xref>)</td>
<td valign="top" align="center">Taiwan, China</td>
<td valign="top" align="center">CS</td>
<td valign="top" align="center">2</td>
<td valign="top" align="center" colspan="2">285</td>
<td valign="top" align="center" colspan="2">NR</td>
<td valign="top" align="center" colspan="2">&#x02265;65</td>
<td valign="top" align="center">ST &#x02265; 12 h/day</td>
<td valign="top" align="center">ST &#x0003C; 8 h/day</td>
<td valign="top" align="center">MCI (&#x02460;)</td>
</tr>
<tr>
<td valign="top" align="left">a. Nemoto et al. (<xref ref-type="bibr" rid="B38">2018</xref>)</td>
<td valign="top" align="center">Japan</td>
<td valign="top" align="center">CSS</td>
<td valign="top" align="center">1</td>
<td valign="top" align="center">1,389</td>
<td valign="top" align="center">952</td>
<td valign="top" align="center" colspan="2">NR</td>
<td valign="top" align="center" colspan="2">&#x02265;65</td>
<td valign="top" align="center">Television viewing time 1&#x02013;2 h/day/2&#x02013;3 h/day/&#x02265;3 h/day</td>
<td valign="top" align="center">Television viewing time &#x0003C; 1 h/day</td>
<td valign="top" align="center">MCI</td>
</tr>
 <tr>
<td/>
<td/>
<td/>
<td/>
<td valign="top" align="center">1,254</td>
<td/>
<td/>
<td/>
<td/>
<td/>
<td/>
<td/>
<td/>
</tr>
 <tr>
<td/>
<td/>
<td/>
<td/>
<td valign="top" align="center">1,427</td>
<td/>
<td/>
<td/>
<td/>
<td/>
<td/>
<td/>
<td/>
</tr>
<tr>
<td valign="top" align="left">b. Nemoto et al. (<xref ref-type="bibr" rid="B38">2018</xref>)</td>
<td valign="top" align="center">Japan</td>
<td valign="top" align="center">CSS</td>
<td valign="top" align="center">1</td>
<td valign="top" align="center">1,240</td>
<td valign="top" align="center">1,094</td>
<td valign="top" align="center" colspan="2">NR</td>
<td valign="top" align="center" colspan="2">&#x02265;65</td>
<td valign="top" align="center">Time of reading books or newspapers 10&#x02013;20 min/day/20&#x02013;30 min/day/&#x02265;30 min/day</td>
<td valign="top" align="center">Time of reading books or newspapers &#x0003C; 10 min/day</td>
<td valign="top" align="center">MCI</td>
</tr>
 <tr>
<td/>
<td/>
<td/>
<td/>
<td valign="top" align="center">1,173</td>
<td/>
<td/>
<td/>
<td/>
<td/>
<td/>
<td/>
<td/>
</tr>
 <tr>
<td/>
<td/>
<td/>
<td/>
<td valign="top" align="center">1,458</td>
<td/>
<td/>
<td/>
<td/>
<td/>
<td/>
<td/>
<td/>
</tr>
<tr>
<td valign="top" align="left">Garc&#x000ED;a-Hermoso et al. (<xref ref-type="bibr" rid="B16">2018</xref>)</td>
<td valign="top" align="center">Chile</td>
<td valign="top" align="center">CSS</td>
<td valign="top" align="center">2</td>
<td valign="top" align="center">416/369</td>
<td valign="top" align="center">573/620</td>
<td valign="top" align="center" colspan="2">NR</td>
<td valign="top" align="center" colspan="2">74.13 &#x000B1; 6.95</td>
<td valign="top" align="center">Sedentary &#x02265; 4 h/day/inactive &#x0003C; 600 METs value min/week</td>
<td valign="top" align="center">Active &#x02265; 600 METs value min/week/non-sedentary &#x0003C; 4 h/day</td>
<td valign="top" align="center">MCI (&#x02461;)</td>
</tr>
 <tr>
<td/>
<td/>
<td/>
<td/>
<td valign="top" align="center">416/620</td>
<td/>
<td valign="top" align="center" colspan="2"></td>
<td valign="top" align="center" colspan="2"></td>
<td valign="top" align="center">Sedentary/active</td>
<td/>
<td/>
</tr>
<tr>
<td valign="top" align="left">Dogra and Stathokostas (<xref ref-type="bibr" rid="B8">2012</xref>)</td>
<td valign="top" align="center">Canada</td>
<td valign="top" align="center">CSS</td>
<td valign="top" align="center">1</td>
<td valign="top" align="center">3,204</td>
<td valign="top" align="center">4,862</td>
<td valign="top" align="center">54.40%</td>
<td valign="top" align="center">56.40%</td>
<td valign="top" align="center" colspan="2">&#x02265;65</td>
<td valign="top" align="center">Moderately sedentary 2&#x02013;4 h/day/Least sedentary &#x0003C; 2 h/day</td>
<td valign="top" align="center">Sedentary &#x0003E; 4 h/day</td>
<td valign="top" align="center">MCI</td>
</tr>
 <tr>
<td/>
<td/>
<td/>
<td/>
<td valign="top" align="center">1,412</td>
<td/>
<td valign="top" align="center">53.00%</td>
<td/>
<td valign="top" align="center" colspan="2"></td>
<td/>
<td/>
</tr>
<tr>
<td valign="top" align="left">Vancampfort et al. (<xref ref-type="bibr" rid="B52">2018</xref>)</td>
<td valign="top" align="center">China, Ghana, India, Mexico, Russia, and South Africa</td>
<td valign="top" align="center">CSS</td>
<td valign="top" align="center">4</td>
<td valign="top" align="center">3,304</td>
<td valign="top" align="center">29,411</td>
<td valign="top" align="center" colspan="2">NR</td>
<td valign="top" align="center" colspan="2">62.10 &#x000B1; 15.60</td>
<td valign="top" align="center">SB &#x02265; 8 h/day/SB per 1 h increase</td>
<td valign="top" align="center">SB &#x0003C; 8 h/day</td>
<td valign="top" align="center">MCI</td>
</tr>
<tr>
<td valign="top" align="left">Lara et al. (<xref ref-type="bibr" rid="B28">2016</xref>)</td>
<td valign="top" align="center">Spain</td>
<td valign="top" align="center">CSS</td>
<td valign="top" align="center">2</td>
<td valign="top" align="center">1,160</td>
<td valign="top" align="center">1,385</td>
<td valign="top" align="center" colspan="2">NR</td>
<td valign="top" align="center" colspan="2">66.26 &#x000B1; 0.18</td>
<td valign="top" align="center">Low PA</td>
<td valign="top" align="center">Moderate PA</td>
<td valign="top" align="center">MCI</td>
</tr>
<tr>
<td valign="top" align="left">Cui et al. (<xref ref-type="bibr" rid="B7">2021</xref>)</td>
<td valign="top" align="center">China</td>
<td valign="top" align="center">CSS</td>
<td valign="top" align="center">1</td>
<td valign="top" align="center">358</td>
<td valign="top" align="center">733</td>
<td valign="top" align="center" colspan="2">NR</td>
<td valign="top" align="center" colspan="2">70.40 &#x000B1; 6.60</td>
<td valign="top" align="center">SB &#x02265; 5 h/day</td>
<td valign="top" align="center">SB &#x0003C; 5 h/day</td>
<td valign="top" align="center">CD&#x0002B;MCI (&#x02461;)</td>
</tr>
<tr>
<td valign="top" align="left">Du et al. (<xref ref-type="bibr" rid="B10">2022</xref>)</td>
<td valign="top" align="center">China</td>
<td valign="top" align="center">CSS</td>
<td valign="top" align="center">1</td>
<td valign="top" align="center">139</td>
<td valign="top" align="center">287</td>
<td valign="top" align="center">47.40%</td>
<td valign="top" align="center">46.70%</td>
<td valign="top" align="center" colspan="2">69.90 &#x000B1; 5.80</td>
<td valign="top" align="center">SB &#x02265; 8 h/day</td>
<td valign="top" align="center">SB &#x0003C; 8 h/day</td>
<td valign="top" align="center">MCI (&#x02461;)</td>
</tr>
<tr>
<td valign="top" align="left">Gillum et al. (<xref ref-type="bibr" rid="B17">2015</xref>)</td>
<td valign="top" align="center">US</td>
<td valign="top" align="center">CSS</td>
<td valign="top" align="center">2</td>
<td valign="top" align="center">194</td>
<td valign="top" align="center">1,162</td>
<td valign="top" align="center" colspan="2">NR</td>
<td valign="top" align="center" colspan="2">&#x02265;60</td>
<td valign="top" align="center">Sitting screen-hours &#x0003E; 3 h/day</td>
<td valign="top" align="center">Sitting screen-hours-3.1 in others</td>
<td valign="top" align="center">MCI</td>
</tr>
<tr>
<td valign="top" align="left">Jung and Chung (<xref ref-type="bibr" rid="B21">2020</xref>)</td>
<td valign="top" align="center">Korea</td>
<td valign="top" align="center">CSS</td>
<td valign="top" align="center">1</td>
<td valign="top" align="center">7,888</td>
<td valign="top" align="center">1,776</td>
<td valign="top" align="center">59.40%</td>
<td valign="top" align="center">52.02%</td>
<td valign="top" align="center">74.08 &#x000B1; 6.50</td>
<td valign="top" align="center">72.50 &#x000B1; 6.14</td>
<td valign="top" align="center">TV viewing</td>
<td valign="top" align="center">Not involved in TV viewing</td>
<td valign="top" align="center">MCI (&#x02461;)</td>
</tr>
<tr>
<td valign="top" align="left">Mart&#x000ED;nez-Sanguinetti et al. (<xref ref-type="bibr" rid="B35">2019</xref>)</td>
<td valign="top" align="center">Chile</td>
<td valign="top" align="center">CSS</td>
<td valign="top" align="center">2</td>
<td valign="top" align="center">169</td>
<td valign="top" align="center">1,215</td>
<td valign="top" align="center" colspan="2">NR</td>
<td valign="top" align="center" colspan="2">&#x02265;60</td>
<td valign="top" align="center">High SB &#x02265; 4 h/day</td>
<td valign="top" align="center">Low SB &#x0003C; 4 h/day</td>
<td valign="top" align="center">MCI (&#x02461;)</td>
</tr>
<tr>
<td valign="top" align="left">Paulo et al. (<xref ref-type="bibr" rid="B40">2016</xref>)</td>
<td valign="top" align="center">Brazil</td>
<td valign="top" align="center">CSS</td>
<td valign="top" align="center">1</td>
<td valign="top" align="center">51</td>
<td valign="top" align="center">340</td>
<td valign="top" align="center">64.70%</td>
<td valign="top" align="center">60.60%</td>
<td valign="top" align="center" colspan="2">71.07 &#x000B1; 7.77</td>
<td valign="top" align="center">Physical inactivity &#x0003C; 150 min of MVPA/week</td>
<td valign="top" align="center">PA &#x02265; 150 min of MVPA/week</td>
<td valign="top" align="center">MCI (&#x02461;)</td>
</tr>
<tr>
<td valign="top" align="left">Poblete-Valderrama et al. (<xref ref-type="bibr" rid="B43">2019</xref>)</td>
<td valign="top" align="center">Chile</td>
<td valign="top" align="center">CSS</td>
<td valign="top" align="center">2</td>
<td valign="top" align="center">169</td>
<td valign="top" align="center">1,215</td>
<td valign="top" align="center" colspan="2">NR</td>
<td valign="top" align="center" colspan="2">&#x0003E;60</td>
<td valign="top" align="center">High SB 4&#x02013;8 h/day/very high SB &#x0003E; 8 h/day</td>
<td valign="top" align="center">Low SB &#x0003C; 4 h/day</td>
<td valign="top" align="center">MCI (&#x02461;)</td>
</tr>
</tbody>
</table>
<table-wrap-foot>
<p>CD, cognitive decline; CG, control group; CS, cohort study; CSS, cross-sectional study; EG, exposure group; MCI, mild cognitive impairment; METs, metabolic equivalants; MVPA, moderate to vigorous physical activity; NR, no reported; Outcome: AD8 (ascertain dementia8); MMSE (mini-mental state examination); PA, physical activity; PAL, physical activity level; SB, sedentary behavior; SD, standard deviation; ST, sedentary time. In addition, a. Nemoto and b. Nemoto are the same article. The characteristics of different exposure groups in the same article are distinguished by/markers.</p>
</table-wrap-foot>
</table-wrap>
</sec>
<sec>
<title>Quality of the included studies</title>
<p>According to the quality evaluation standard, 17 of the articles were high-quality studies, while two were medium-quality studies. One study met all the quality evaluation criteria. Three studies were limited by one factor, and the others were limited by at least two factors, with a research quality score of 6&#x02013;9. The loss-to-follow-up rate of two articles was &#x0003E;25%, and the follow-up period of three articles was &#x0003C;5 years. All articles did not provide clarity regarding whether the evaluators&#x00027; factors covered other aspects of the research object. Furthermore, it remains unclear whether follow-up data were available, including information on the expected population with incomplete data or follow-up results. Seven articles explained how missing data were handled in the analysis. The quality assessment of the included studies is specified in <xref ref-type="supplementary-material" rid="SM6">Supplementary Tables 1</xref>, <xref ref-type="supplementary-material" rid="SM7">2</xref>.</p>
</sec>
<sec>
<title>Results of traditional meta-analysis</title>
<sec>
<title>Association between SB and the risk of CD in the elderly</title>
<p>Five articles investigated the relationship between SB and the risk of CD in the elderly, with a sample size of 8,439 cases (Ferreira et al., <xref ref-type="bibr" rid="B12">2010</xref>; Lee et al., <xref ref-type="bibr" rid="B29">2013</xref>; Gomes et al., <xref ref-type="bibr" rid="B18">2017</xref>; Ku et al., <xref ref-type="bibr" rid="B26">2017a</xref>; Song and Park, <xref ref-type="bibr" rid="B47">2022</xref>). The heterogeneity test showed that there was no heterogeneity among the studies (<italic>I</italic><sup>2</sup> = 15.50%, <italic>P</italic><sub>heterogeneity</sub> = 0.30); thus, the fixed effect model was used for meta-analysis. The combined meta-analysis results demonstrated a significant difference between the two groups (OR = 1.69, 95% CI: 1.47&#x02013;1.94, <italic>P</italic> &#x0003C; 0.01), and long-term SB was found to increase the risk of CD in the elderly compared to the control group, as shown in <xref ref-type="fig" rid="F2">Figure 2</xref> and <xref ref-type="table" rid="T2">Table 2</xref>. The funnel diagram was relatively symmetrical, and Egger&#x00027;s test suggested that there was no publication bias within the studies (<inline-formula><mml:math id="M1"><mml:msub><mml:mrow><mml:mi>P</mml:mi></mml:mrow><mml:mrow><mml:mtext>Egge</mml:mtext><mml:msup><mml:mrow><mml:mtext>r</mml:mtext></mml:mrow><mml:mrow><mml:mtext>&#x02032;</mml:mtext></mml:mrow></mml:msup><mml:mtext>stest</mml:mtext></mml:mrow></mml:msub></mml:math></inline-formula> = 0.19), as shown in <xref ref-type="supplementary-material" rid="SM2">Supplementary Figures 1</xref>, <xref ref-type="supplementary-material" rid="SM3">2</xref>.</p>
<fig id="F2" position="float">
<label>Figure 2</label>
<caption><p>Forest plot of cognitive decline (CD).</p></caption>
<graphic mimetype="image" mime-subtype="tiff" xlink:href="fnins-17-1221990-g0002.tif"/>
</fig>
<table-wrap position="float" id="T2">
<label>Table 2</label>
<caption><p>Results of traditional meta-analysis and subgroup analyses.</p></caption> 
<table frame="box" rules="all">
<thead>
<tr style="background-color:&#x00023;919498;color:&#x00023;ffffff">
<th valign="top" align="left" colspan="2"><bold>Meta-analyses outcomes/subgroup</bold></th>
<th valign="top" align="center"><bold>Number of studies</bold></th>
<th valign="top" align="center"><bold>OR, 95% CI</bold></th>
<th valign="top" align="center" colspan="2"><bold>Heterogeneity</bold></th>
<th valign="top" align="center"><bold>Effect model</bold></th>
</tr>
</thead>
<tbody>
<tr style="background-color:&#x00023;919498;color:&#x00023;ffffff">
<td valign="top" align="center" colspan="2"></td>
<td/>
<td/>
<td valign="top" align="center"><italic><bold>P</bold></italic></td>
<td valign="top" align="center"><italic>I</italic><sup>2</sup> <bold>(%)</bold></td>
<td/>
</tr>
<tr style="background-color:#dee1e1">
<td valign="top" align="left" colspan="7"><bold>Meta-analysis of the association between SB and risk of CD or MCI in elderly</bold></td>
</tr>
<tr>
<td valign="top" align="center" colspan="2">(High vs. Low) SB &#x0002B; CD</td>
<td valign="top" align="center">5</td>
<td valign="top" align="center">1.69 (1.47, 1.94)</td>
<td valign="top" align="center">0.30</td>
<td valign="top" align="center">15.50</td>
<td valign="top" align="center">Fixed effect model</td>
</tr>
<tr>
<td valign="top" align="center" colspan="2">(High vs. Low) SB &#x0002B; MCI</td>
<td valign="top" align="center">14</td>
<td valign="top" align="center">1.34 (1.14, 1.56)</td>
<td valign="top" align="center">&#x0003C; 0.10</td>
<td valign="top" align="center">92.70</td>
<td valign="top" align="center">Random effects model</td>
</tr>
<tr style="background-color:#dee1e1">
<td valign="top" align="left" colspan="7"><bold>Results of subgroup analyses about SB and the risk of CD in elderly</bold></td>
</tr>
<tr>
<td valign="top" align="left">Duration of follow-up</td>
<td valign="top" align="center">Overall</td>
<td valign="top" align="center">5</td>
<td valign="top" align="center">1.69 (1.47, 1.94)</td>
<td valign="top" align="center">0.30</td>
<td valign="top" align="center">15.50</td>
<td valign="top" align="center">Fixed effect model</td>
</tr>
 <tr>
<td/>
<td valign="top" align="center">&#x02265;3 years</td>
<td valign="top" align="center">3</td>
<td valign="top" align="center">2.03 (1.63, 2.53)</td>
<td valign="top" align="center">0.80</td>
<td valign="top" align="center">0.00</td>
<td valign="top" align="center">Fixed effect model</td>
</tr>
 <tr>
<td/>
<td valign="top" align="center">&#x0003C; 3 years</td>
<td valign="top" align="center">2</td>
<td valign="top" align="center">1.05 (1.25, 1.79)</td>
<td valign="top" align="center">0.25</td>
<td valign="top" align="center">27.40</td>
<td valign="top" align="center">Fixed effect model</td>
</tr>
<tr>
<td valign="top" align="left">Region</td>
<td valign="top" align="center">Overall</td>
<td valign="top" align="center">5</td>
<td valign="top" align="center">1.69 (1.47, 1.94)</td>
<td valign="top" align="center">0.30</td>
<td valign="top" align="center">15.50</td>
<td valign="top" align="center">Fixed effect model</td>
</tr>
 <tr>
<td/>
<td valign="top" align="center">Developed countries</td>
<td valign="top" align="center">3</td>
<td valign="top" align="center">1.72 (1.46, 2.03)</td>
<td valign="top" align="center">0.39</td>
<td valign="top" align="center">2.90</td>
<td valign="top" align="center">Fixed effect model</td>
</tr>
 <tr>
<td/>
<td valign="top" align="center">Developing or underdeveloped countries</td>
<td valign="top" align="center">2</td>
<td valign="top" align="center">1.61 (1.25, 2.09)</td>
<td valign="top" align="center">0.12</td>
<td valign="top" align="center">51.70</td>
<td valign="top" align="center">Fixed effect model</td>
</tr>
<tr>
<td valign="top" align="left">Publication year</td>
<td valign="top" align="center">Overall</td>
<td valign="top" align="center">5</td>
<td valign="top" align="center">1.69 (1.47, 1.94)</td>
<td valign="top" align="center">0.30</td>
<td valign="top" align="center">15.50</td>
<td valign="top" align="center">Fixed effect model</td>
</tr>
 <tr>
<td/>
<td valign="top" align="center">&#x02265;2017</td>
<td valign="top" align="center">3</td>
<td valign="top" align="center">1.64 (1.41, 1.91)</td>
<td valign="top" align="center">0.15</td>
<td valign="top" align="center">40.50</td>
<td valign="top" align="center">Fixed effect model</td>
</tr>
 <tr>
<td/>
<td valign="top" align="center">&#x0003C; 2017</td>
<td valign="top" align="center">2</td>
<td valign="top" align="center">1.93 (1.40, 2.66)</td>
<td valign="top" align="center">0.58</td>
<td valign="top" align="center">0.00</td>
<td valign="top" align="center">Fixed effect model</td>
</tr>
<tr>
<td valign="top" align="left">Total sample size</td>
<td valign="top" align="center">Overall</td>
<td valign="top" align="center">5</td>
<td valign="top" align="center">1.69 (1.47, 1.94)</td>
<td valign="top" align="center">0.30</td>
<td valign="top" align="center">15.50</td>
<td valign="top" align="center">Fixed effect model</td>
</tr>
 <tr>
<td/>
<td valign="top" align="center">&#x02265;1,000</td>
<td valign="top" align="center">2</td>
<td valign="top" align="center">1.71 (1.43, 2.04)</td>
<td valign="top" align="center">0.19</td>
<td valign="top" align="center">38.80</td>
<td valign="top" align="center">Fixed effect model</td>
</tr>
 <tr>
<td/>
<td valign="top" align="center">&#x0003C; 1,000</td>
<td valign="top" align="center">3</td>
<td valign="top" align="center">1.67 (1.34, 2.08)</td>
<td valign="top" align="center">0.28</td>
<td valign="top" align="center">19.00</td>
<td valign="top" align="center">Fixed effect model</td>
</tr>
<tr>
<td valign="top" align="left">SB exposure time</td>
<td valign="top" align="center">Overall</td>
<td valign="top" align="center">5</td>
<td valign="top" align="center">1.69 (1.47, 1.94)</td>
<td valign="top" align="center">0.30</td>
<td valign="top" align="center">15.50</td>
<td valign="top" align="center">Fixed effect model</td>
</tr>
 <tr>
<td/>
<td valign="top" align="center">&#x02265;5 h/day</td>
<td valign="top" align="center">2</td>
<td valign="top" align="center">1.58 (1.23, 2.02)</td>
<td valign="top" align="center">0.26</td>
<td valign="top" align="center">23.10</td>
<td valign="top" align="center">Fixed effect model</td>
</tr>
 <tr>
<td/>
<td valign="top" align="center">&#x0003C; 5 h/day</td>
<td valign="top" align="center">3</td>
<td valign="top" align="center">1.75 (1.48, 2.07)</td>
<td valign="top" align="center">0.28</td>
<td valign="top" align="center">21.20</td>
<td valign="top" align="center">Fixed effect model</td>
</tr>
<tr>
<td valign="top" align="left">Complications</td>
<td valign="top" align="center">Overall</td>
<td valign="top" align="center">5</td>
<td valign="top" align="center">1.69 (1.47, 1.94)</td>
<td valign="top" align="center">0.30</td>
<td valign="top" align="center">15.50</td>
<td valign="top" align="center">Fixed effect model</td>
</tr>
 <tr>
<td/>
<td valign="top" align="center">Yes</td>
<td valign="top" align="center">5</td>
<td valign="top" align="center">1.69 (1.47, 1.94)</td>
<td valign="top" align="center">0.30</td>
<td valign="top" align="center">15.50</td>
<td valign="top" align="center">Fixed effect model</td>
</tr>
 <tr>
<td/>
<td valign="top" align="center">No</td>
<td/>
<td valign="top" align="center">&#x02013;</td>
<td valign="top" align="center">&#x02013;</td>
<td valign="top" align="center">&#x02013;</td>
<td valign="top" align="center">&#x02013;</td>
</tr>
<tr>
<td valign="top" align="left">Comorbidities</td>
<td valign="top" align="center">Overall</td>
<td valign="top" align="center">5</td>
<td valign="top" align="center">1.69 (1.47, 1.94)</td>
<td valign="top" align="center">0.30</td>
<td valign="top" align="center">15.50</td>
<td valign="top" align="center">Fixed effect model</td>
</tr>
 <tr>
<td/>
<td valign="top" align="center">Adjusted</td>
<td valign="top" align="center">5</td>
<td valign="top" align="center">1.69 (1.47, 1.94)</td>
<td valign="top" align="center">0.30</td>
<td valign="top" align="center">15.50</td>
<td valign="top" align="center">Fixed effect model</td>
</tr>
 <tr>
<td/>
<td valign="top" align="center">Unadjusted</td>
<td/>
<td valign="top" align="center">&#x02013;</td>
<td valign="top" align="center">&#x02013;</td>
<td valign="top" align="center">&#x02013;</td>
<td valign="top" align="center">&#x02013;</td>
</tr>
<tr>
<td valign="top" align="left">Lifestyle</td>
<td valign="top" align="center">Overall</td>
<td valign="top" align="center">5</td>
<td valign="top" align="center">1.69 (1.47, 1.94)</td>
<td valign="top" align="center">0.30</td>
<td valign="top" align="center">15.50</td>
<td valign="top" align="center">Fixed effect model</td>
</tr>
 <tr>
<td/>
<td valign="top" align="center">Adjusted</td>
<td valign="top" align="center">3</td>
<td valign="top" align="center">1.78 (1.47, 2.15)</td>
<td valign="top" align="center">0.26</td>
<td valign="top" align="center">21.60</td>
<td valign="top" align="center">Fixed effect model</td>
</tr>
 <tr>
<td/>
<td valign="top" align="center">Unadjusted</td>
<td valign="top" align="center">2</td>
<td valign="top" align="center">1.60 (1.31, 1.96)</td>
<td valign="top" align="center">0.25</td>
<td valign="top" align="center">23.10</td>
<td valign="top" align="center">Fixed effect model</td>
</tr>
<tr>
<td valign="top" align="left">Family structure</td>
<td valign="top" align="center">Overall</td>
<td valign="top" align="center">5</td>
<td valign="top" align="center">1.69 (1.47, 1.94)</td>
<td valign="top" align="center">0.30</td>
<td valign="top" align="center">15.50</td>
<td valign="top" align="center">Fixed effect model</td>
</tr>
 <tr>
<td/>
<td valign="top" align="center">Adjusted</td>
<td valign="top" align="center">2</td>
<td valign="top" align="center">1.76 (1.42, 2.19)</td>
<td valign="top" align="center">0.12</td>
<td valign="top" align="center">48.60</td>
<td valign="top" align="center">Fixed effect model</td>
</tr>
 <tr>
<td/>
<td valign="top" align="center">Unadjusted</td>
<td valign="top" align="center">3</td>
<td valign="top" align="center">1.64 (1.37, 1.97)</td>
<td valign="top" align="center">0.49</td>
<td valign="top" align="center">0.00</td>
<td valign="top" align="center">Fixed effect model</td>
</tr>
<tr style="background-color:#dee1e1">
<td valign="top" align="left" colspan="7"><bold>Results of subgroup analyses about SB and the risk of MCI in elderly</bold></td>
</tr>
<tr>
<td valign="top" align="left">Duration of follow-up</td>
<td valign="top" align="center">Overall</td>
<td valign="top" align="center">14</td>
<td valign="top" align="center">1.34 (1.14, 1.56)</td>
<td valign="top" align="center">0.00</td>
<td valign="top" align="center">92.70</td>
<td valign="top" align="center">Random effects model</td>
</tr>
 <tr>
<td/>
<td valign="top" align="center">&#x02265;3 years</td>
<td valign="top" align="center">2</td>
<td valign="top" align="center">1.27 (0.99, 1.62)</td>
<td valign="top" align="center">0.00</td>
<td valign="top" align="center">85.50</td>
<td valign="top" align="center">Random effects model</td>
</tr>
 <tr>
<td/>
<td valign="top" align="center">&#x0003C; 3 years</td>
<td valign="top" align="center">12</td>
<td valign="top" align="center">1.41 (1.11, 1.78)</td>
<td valign="top" align="center">0.00</td>
<td valign="top" align="center">93.40</td>
<td valign="top" align="center">Random effects model</td>
</tr>
<tr>
<td valign="top" align="left">Region</td>
<td valign="top" align="center">Overall</td>
<td valign="top" align="center">14</td>
<td valign="top" align="center">1.34 (1.14, 1.56)</td>
<td valign="top" align="center">0.00</td>
<td valign="top" align="center">92.70</td>
<td valign="top" align="center">Random effects model</td>
</tr>
 <tr>
<td/>
<td valign="top" align="center">Developed countries</td>
<td valign="top" align="center">6</td>
<td valign="top" align="center">0.99 (0.79, 1.23)</td>
<td valign="top" align="center">0.00</td>
<td valign="top" align="center">92.90</td>
<td valign="top" align="center">Random effects model</td>
</tr>
 <tr>
<td/>
<td valign="top" align="center">Developing or Underdeveloped countries</td>
<td valign="top" align="center">8</td>
<td valign="top" align="center">2.18 (1.53, 3.09)</td>
<td valign="top" align="center">0.00</td>
<td valign="top" align="center">92.10</td>
<td valign="top" align="center">Random effects model</td>
</tr>
<tr>
<td valign="top" align="left">Publication year</td>
<td valign="top" align="center">Overall</td>
<td valign="top" align="center">14</td>
<td valign="top" align="center">1.34 (1.14, 1.56)</td>
<td valign="top" align="center">0.00</td>
<td valign="top" align="center">92.70</td>
<td valign="top" align="center">Random effects model</td>
</tr>
 <tr>
<td/>
<td valign="top" align="center">&#x02265;2017</td>
<td valign="top" align="center">9</td>
<td valign="top" align="center">1.39 (1.14, 1.70)</td>
<td valign="top" align="center">0.00</td>
<td valign="top" align="center">94.50</td>
<td valign="top" align="center">Random effects model</td>
</tr>
 <tr>
<td/>
<td valign="top" align="center">&#x0003C; 2017</td>
<td valign="top" align="center">5</td>
<td valign="top" align="center">1.25 (1.10, 1.42)</td>
<td valign="top" align="center">0.34</td>
<td valign="top" align="center">11.60</td>
<td valign="top" align="center">Random effects model</td>
</tr>
<tr>
<td valign="top" align="left">Total sample size</td>
<td valign="top" align="center">Overall</td>
<td valign="top" align="center">14</td>
<td valign="top" align="center">1.34 (1.14, 1.56)</td>
<td valign="top" align="center">0.00</td>
<td valign="top" align="center">92.70</td>
<td valign="top" align="center">Random effects model</td>
</tr>
 <tr>
<td/>
<td valign="top" align="center">&#x02265;1,000</td>
<td valign="top" align="center">10</td>
<td valign="top" align="center">1.14 (0.98, 1.33)</td>
<td valign="top" align="center">0.00</td>
<td valign="top" align="center">91.90</td>
<td valign="top" align="center">Random effects model</td>
</tr>
 <tr>
<td/>
<td valign="top" align="center">&#x0003C; 1,000</td>
<td valign="top" align="center">4</td>
<td valign="top" align="center">2.77 (1.47, 5.21)</td>
<td valign="top" align="center">0.00</td>
<td valign="top" align="center">85.00</td>
<td valign="top" align="center">Random effects model</td>
</tr>
<tr>
<td valign="top" align="left">SB exposure time</td>
<td valign="top" align="center">Overall</td>
<td valign="top" align="center">14</td>
<td valign="top" align="center">1.34 (1.14, 1.56)</td>
<td valign="top" align="center">0.00</td>
<td valign="top" align="center">92.70</td>
<td valign="top" align="center">Random effects model</td>
</tr>
 <tr>
<td/>
<td valign="top" align="center">&#x02265;5 h/day</td>
<td valign="top" align="center">8</td>
<td valign="top" align="center">1.42 (1.14, 1.78)</td>
<td valign="top" align="center">0.00</td>
<td valign="top" align="center">94.70</td>
<td valign="top" align="center">Random effects model</td>
</tr>
 <tr>
<td/>
<td valign="top" align="center">&#x0003C; 5 h/day</td>
<td valign="top" align="center">6</td>
<td valign="top" align="center">1.26 (1.16, 1.37)</td>
<td valign="top" align="center">0.46</td>
<td valign="top" align="center">0.00</td>
<td valign="top" align="center">Random effects model</td>
</tr>
<tr>
<td valign="top" align="left">Complications</td>
<td valign="top" align="center">Overall</td>
<td valign="top" align="center">14</td>
<td valign="top" align="center">1.34 (1.14, 1.56)</td>
<td valign="top" align="center">0.00</td>
<td valign="top" align="center">92.70</td>
<td valign="top" align="center">Random effects model</td>
</tr>
 <tr>
<td/>
<td valign="top" align="center">Yes</td>
<td valign="top" align="center">13</td>
<td valign="top" align="center">1.37 (1.15, 1.62)</td>
<td valign="top" align="center">0.00</td>
<td valign="top" align="center">93.40</td>
<td valign="top" align="center">Random effects model</td>
</tr>
 <tr>
<td/>
<td valign="top" align="center">No</td>
<td valign="top" align="center">1</td>
<td valign="top" align="center">1.16 (0.98, 1.38)</td>
<td valign="top" align="center">0.52</td>
<td valign="top" align="center">0.00</td>
<td valign="top" align="center">Random effects model</td>
</tr>
<tr>
<td valign="top" align="left">Comorbidities</td>
<td valign="top" align="center">Overall</td>
<td valign="top" align="center">14</td>
<td valign="top" align="center">1.34 (1.14, 1.56)</td>
<td valign="top" align="center">0.00</td>
<td valign="top" align="center">92.70</td>
<td valign="top" align="center">Random effects model</td>
</tr>
 <tr>
<td/>
<td valign="top" align="center">Adjusted</td>
<td valign="top" align="center">12</td>
<td valign="top" align="center">1.34 (1.12, 1.59)</td>
<td valign="top" align="center">0.00</td>
<td valign="top" align="center">93.50</td>
<td valign="top" align="center">Random effects model</td>
</tr>
 <tr>
<td/>
<td valign="top" align="center">Unadjusted</td>
<td valign="top" align="center">2</td>
<td valign="top" align="center">1.33 (0.97, 1.83)</td>
<td valign="top" align="center">0.04</td>
<td valign="top" align="center">68.10</td>
<td valign="top" align="center">Random effects model</td>
</tr>
<tr>
<td valign="top" align="left">Lifestyle</td>
<td valign="top" align="center">Overall</td>
<td valign="top" align="center">14</td>
<td valign="top" align="center">1.34 (1.14, 1.56)</td>
<td valign="top" align="center">0.00</td>
<td valign="top" align="center">92.70</td>
<td valign="top" align="center">Random effects model</td>
</tr>
 <tr>
<td/>
<td valign="top" align="center">Adjusted</td>
<td valign="top" align="center">10</td>
<td valign="top" align="center">1.32 (1.10, 1.59)</td>
<td valign="top" align="center">0.00,</td>
<td valign="top" align="center">94.00</td>
<td valign="top" align="center">Random effects model</td>
</tr>
 <tr>
<td/>
<td valign="top" align="center">Unadjusted</td>
<td valign="top" align="center">4</td>
<td valign="top" align="center">1.38 (1.08, 1.77)</td>
<td valign="top" align="center">0.02</td>
<td valign="top" align="center">63.60</td>
<td valign="top" align="center">Random effects model</td>
</tr>
<tr>
<td valign="top" align="left">Family structure</td>
<td valign="top" align="center">Overall</td>
<td valign="top" align="center">14</td>
<td valign="top" align="center">1.34 (1.14, 1.56)</td>
<td valign="top" align="center">0.00</td>
<td valign="top" align="center">92.70</td>
<td valign="top" align="center">Random effects model</td>
</tr>
 <tr>
<td/>
<td valign="top" align="center">Adjusted</td>
<td valign="top" align="center">7</td>
<td valign="top" align="center">1.27 (0.96, 1.69)</td>
<td valign="top" align="center">0.00</td>
<td valign="top" align="center">94.50</td>
<td valign="top" align="center">Random effects model</td>
</tr>
<tr>
<td/>
<td valign="top" align="center">Unadjusted</td>
<td valign="top" align="center">7</td>
<td valign="top" align="center">1.49 (1.24, 1.79)</td>
<td valign="top" align="center">0.00</td>
<td valign="top" align="center">83.30</td>
<td valign="top" align="center">Random effects model</td>
</tr>
</tbody>
</table>
<table-wrap-foot>
<p>SB, sedentary behavior; CD, cognitive decline; MCI, mild cognitive impairment.</p>
</table-wrap-foot>
</table-wrap>
</sec>
<sec>
<title>Association between SB and the risk of MCI in the elderly</title>
<p>In total, 14 articles investigated the relationship between SB and the risk of MCI in the elderly, with a sample size of 73,352 cases (Dogra and Stathokostas, <xref ref-type="bibr" rid="B8">2012</xref>; Gillum et al., <xref ref-type="bibr" rid="B17">2015</xref>; Lara et al., <xref ref-type="bibr" rid="B28">2016</xref>; Paulo et al., <xref ref-type="bibr" rid="B40">2016</xref>; Brunner et al., <xref ref-type="bibr" rid="B3">2017</xref>; Ku et al., <xref ref-type="bibr" rid="B25">2017b</xref>; Garc&#x000ED;a-Hermoso et al., <xref ref-type="bibr" rid="B16">2018</xref>; Nemoto et al., <xref ref-type="bibr" rid="B38">2018</xref>; Vancampfort et al., <xref ref-type="bibr" rid="B52">2018</xref>; Mart&#x000ED;nez-Sanguinetti et al., <xref ref-type="bibr" rid="B35">2019</xref>; Poblete-Valderrama et al., <xref ref-type="bibr" rid="B43">2019</xref>; Jung and Chung, <xref ref-type="bibr" rid="B21">2020</xref>; Cui et al., <xref ref-type="bibr" rid="B7">2021</xref>; Du et al., <xref ref-type="bibr" rid="B10">2022</xref>). The heterogeneity test showed that the studies were heterogenous (<italic>I</italic><sup>2</sup> = 92.70%, <italic>P</italic><sub>heterogeneity</sub> &#x0003C; 0.10), and a random effects model was used for the meta-analysis. The combined results showed a significant difference between the two groups (OR = 1.34, 95% CI: 1.14&#x02013;1.56, <italic>P</italic> &#x0003C; 0.01), and prolonged SB was found to increase the risk of MCI in the elderly compared with control groups, as shown in <xref ref-type="fig" rid="F3">Figure 3</xref> and <xref ref-type="table" rid="T2">Table 2</xref>. The funnel diagram was relatively symmetrical, and Egger&#x00027;s test suggested that there was no publication bias within the studies (<inline-formula><mml:math id="M2"><mml:msub><mml:mrow><mml:mi>P</mml:mi></mml:mrow><mml:mrow><mml:mtext>Egge</mml:mtext><mml:msup><mml:mrow><mml:mtext>r</mml:mtext></mml:mrow><mml:mrow><mml:mtext>&#x02032;</mml:mtext></mml:mrow></mml:msup><mml:mtext>stest</mml:mtext></mml:mrow></mml:msub></mml:math></inline-formula> = 0.20), as shown in <xref ref-type="supplementary-material" rid="SM4">Supplementary Figures 3</xref>, <xref ref-type="supplementary-material" rid="SM5">4</xref>.</p>
<fig id="F3" position="float">
<label>Figure 3</label>
<caption><p>Forest plot of mild cognitive impairment (MCI).</p></caption>
<graphic mimetype="image" mime-subtype="tiff" xlink:href="fnins-17-1221990-g0003.tif"/>
</fig>
</sec>
</sec>
<sec>
<title>Results of subgroup analyses</title>
<p>No subgroup statistical differences were observed in the relationship between SB and the risk of CD across the two groups or were any significant sources of heterogeneity identified. Significant statistical differences were observed in most subgroups regarding the relationship between SB and the risk of MCI. Furthermore, the consistency among these subgroups provided insights into the sources of heterogeneity. Subgroup analysis of SB exposure time showed significantly higher heterogeneity for sedentary time above 5 h/day (OR = 1.42, 95% CI: 1.14&#x02013;1.78, <italic>P</italic><sub>heterogeneity</sub> = 0.00, <italic>I</italic><sup>2</sup> = 94.70%, random model) compared to that within 5 h/day (OR = 1.26, 95% CI: 1.16&#x02013;1.37, <italic>P</italic><sub>heterogeneity</sub> = 0.46, <italic>I</italic><sup>2</sup> = 0.00%, random model) though no difference was observed between these two subgroups. Detailed results for other subgroup analyses are shown in <xref ref-type="table" rid="T2">Table 2</xref>.</p>
</sec>
</sec>
<sec sec-type="discussion" id="s4">
<title>Discussion</title>
<p>This study explored the association between SB and the risk of CD or MCI in the elderly from the perspective of evidence-based medicine. We found that elderly individuals with long-term SB were more likely to develop CD or MCI than those who engaged in physical activity (PA) or had short-term SB, and this trend is even more evident in Asian populations.</p>
<p>This study showed that prolonged SB increased the risk of CD in the elderly (OR = 1.69, 95% CI: 1.47&#x02013;1.94), and there was a significant positive correlation between prolonged SB and increased risk of CD. Related studies have also revealed results consistent with ours (Kesse-Guyot et al., <xref ref-type="bibr" rid="B23">2014</xref>; Falck et al., <xref ref-type="bibr" rid="B11">2017</xref>). In a longitudinal study investigating the association of low PA, SB, smoking, and other lifestyle parameters with cognitive function in 2,430 middle-aged and older adults, Kesse-Guyot et al. (<xref ref-type="bibr" rid="B23">2014</xref>) showed that SB was associated with a decline in overall cognitive function in the elderly. In a systematic review of the association between SB and cognitive function, Falck et al. found that SB is not only associated with a higher risk of type 2 diabetes and cardiovascular disease but can also lead to a decline in overall cognitive, memory, and executive function in elderly individuals (Falck et al., <xref ref-type="bibr" rid="B11">2017</xref>). In a cross-sectional study, Coelho et al. (<xref ref-type="bibr" rid="B6">2020</xref>) found that the negative association between SB and cognitive function was predominantly significant in the elderly with long-term SB. This could be attributed to the fact that with an increase in the sedentary time of elderly individuals, the body correspondingly induces an increase in white matter hyperintensity volume (WMHV), a decrease in the level of brain-derived neurotrophic factor (BD-NF), and a decrease in the level of medial temporal changes such as the thinning of leaf thickness and abnormal cerebral blood flow, which can lead to a decline of cognitive function in the elderly. In conclusion, the mechanisms through which SB causes CD are complex and multifaceted. Possible explanations for the discrepancy between existing relevant evidence (Kesse-Guyot et al., <xref ref-type="bibr" rid="B24">2012</xref>; Hamer and Stamatakis, <xref ref-type="bibr" rid="B19">2014</xref>) and the result of this article are that the sample size of their study was small and unrepresentative and that the short-term follow-up may not have been sufficient to detect a meaningful association between changes in cognition and SB. Moreover, the level of cognitive stimulation in the elderly also varies across SB measurement modes. In contrast, our study employed a comprehensive search strategy and involved multiple databases, and a complementary search was performed for potential literature such as meeting reports and abstracts. Consequently, the sample size of this study is large enough to provide strong evidence of the association under study. In addition, our results also found that prolonged SB significantly increased the risk of MCI in the elderly (OR = 1.34, 95% CI: 1.14&#x02013;1.56), and there was a significant positive correlation between prolonged SB and the risk of MCI, consistent with previous studies (Xie et al., <xref ref-type="bibr" rid="B54">2021</xref>; Gafni et al., <xref ref-type="bibr" rid="B14">2022</xref>). In a cross-sectional study, Xie et al. (<xref ref-type="bibr" rid="B54">2021</xref>) found a significant relationship between excessive SB and MCI in the elderly. Their findings also revealed that limiting sedentary time is important as elderly patients with MCI tend to have a greater sedentary time, thereby leading to more adverse health outcomes. In another cross-sectional study, Gafni et al. (<xref ref-type="bibr" rid="B14">2022</xref>) found that insufficient PA and sitting for at least three-quarters of the day increased the risk of MCI in the elderly. In other words, low PA and prolonged SB adversely affect cognitive function in the elderly (Peng et al., <xref ref-type="bibr" rid="B41">2022</xref>). This could be due to the high prevalence of chronic inflammation and reduced hormone levels associated with older stages of life. Long-term SB aggravates bone loss, reduces the size and quantity of muscle fibers, affects the contraction of skeletal muscles, and accelerates cell aging and brain atrophy, leading to MCI in the elderly. Thus, reducing sedentary time could prevent or retard the development of MCI. Moreover, it is highly recommended that elderly individuals should increase their PA level and improve their sleep quality to enhance their individual cognitive function. Sleep duration, SB, and PA are co-dependent behaviors that constitute the movement/non-movement continuum and together account for the 24-h daily cycle (Zhu et al., <xref ref-type="bibr" rid="B57">2020</xref>). Studies have shown that PA plays a positive role as an effective cognitive intervention in helping to improve cognitive function in older adults with AD or MCI (Liang et al., <xref ref-type="bibr" rid="B31">2018</xref>). A minimum of 150 min of moderate-to-vigorous physical activity (MVPA) per week promotes an increased blood flow to the brain and improves metabolism and cardiovascular health (Liang et al., <xref ref-type="bibr" rid="B31">2018</xref>). Deep sleep plays a crucial role in facilitating the clearance of amyloid-beta (A&#x003B2;) in the brain and improving overall sleep quality (Liang et al., <xref ref-type="bibr" rid="B30">2020</xref>). They contribute to reducing the risk of MCI and dementia in the elderly population (Liang et al., <xref ref-type="bibr" rid="B30">2020</xref>). Therefore, we encourage older adults to meet the 24-h healthy movement guidelines (i.e., &#x02265;60 min of MVPA, &#x02264; 2 h of screentime, and age-appropriate sleep duration) (Zhu et al., <xref ref-type="bibr" rid="B57">2020</xref>) in order to improve their cognitive health outcomes. In addition, we investigated whether there are gender differences in the cognitive impairment caused by SB. Studies have shown that the prevalence of MCI is 1.28 times higher in women than in men (Wang et al., <xref ref-type="bibr" rid="B53">2020</xref>). Men who are engaged in mental work have rich knowledge reserves and strong thinking abilities and are not prone to cognitive impairment (Wang et al., <xref ref-type="bibr" rid="B53">2020</xref>). Therefore, we suggest that elderly individuals should be encouraged to participate in educational activities, such as playing computer games or chess, to exercise their memory and potentially delay cognitive dysfunction.</p>
<p>In the subgroup analysis, we found significant differences between the two groups in terms of lifestyle, comorbidity, and family structure. The reason may be that sedentary elderly individuals live alone for a long time, have reduced daily communication, and find it difficult to overcome loneliness, anxiety, and depression, which could affect their cognitive function. The brain weight of elderly individuals decreases with increasing age, and there is a certain degree of inevitable physiological brain aging (Ma et al., <xref ref-type="bibr" rid="B34">2019</xref>). The emergence of other comorbidities (such as hypertension and diabetes) accelerates the decline and impairment of cognitive function in the elderly. Simultaneously, there were differences in region, publication year, and the duration of SB between the two groups. This is due to the level of regional economic and medical resources, the construction of elderly activity venues, the lengthiness of publication, the short duration of the study, the sample size of the articles, and the quality of the content of the studies. In addition, this study mostly used scales, structured interview questionnaires, and self-reports to measure sedentary behavior, leading to possible bias in the results. Future research should use objective methods to more accurately measure the duration of SB, such as a three-dimensional accelerometer and an inclinometer.</p>
<sec>
<title>Strengths and limitations</title>
<p>To the best of our knowledge, this is the first study to examine the relationship between SB and the risk of CD or MCI in the elderly. Given that this area of research is still developing, our study only provides some insight into the relationship between SB and the risk of CD or MCI in the elderly, providing reliable evidence for the development of future public health policies. The articles included in our study were small, and studies were not of high quality, which may have led to some bias in the interpretation of the results. In addition, the definition of &#x0201C;sedentary behavior&#x0201D; was inconsistent, which might induce bias in effect size estimates. For the evaluation of article quality, the existence of subjective judgment errors could lead to judgment bias. In the future, other assessment methods should be considered to minimize these errors to a great extent. When conducting subgroup analysis, some subgroups included a small number of articles and sample sizes, which reduced the reliability of the results. This requires further validation by high-quality and large-sample studies. This study is based on a systematic review and meta-analysis of observational studies. Most of the articles included in the analysis were from cross-sectional studies, limiting the ability to infer causality. In the future, more high-quality randomized controlled trials (RCTs), Mendelian randomization (MR) studies, or basic research would be needed.</p>
</sec>
</sec>
<sec sec-type="conclusions" id="s5">
<title>Conclusion</title>
<p>In summary, our study reveals a positive association between SB and the risk of CD or MCI in the elderly. Long-term SB increases the risk of CD or MCI in the elderly. We recommend that the elderly reduce their SB time and increase their level of PA to promote healthy cognitive aging. Considering the quantity and quality of the included articles, our findings need to be interpreted with caution, and more high-quality longitudinal studies are required in the future to further demonstrate the association between SB and the risk of CD or MCI in the elderly.</p>
</sec>
<sec sec-type="data-availability" id="s6">
<title>Data availability statement</title>
<p>Data generated or analyzed during this study are included in this published article or in the data repositories listed in the references.</p>
</sec>
<sec sec-type="author-contributions" id="s7">
<title>Author contributions</title>
<p>X-yC served as the principal author, had full access to all data in the study, and took responsibility for the accuracy of the data analysis and the integrity of the data. J-hL and FW contributed to the conception and design. M-yZ, G-pQ, and X-yC contributed to data acquisition and interpretation. X-yC and G-pQ contributed to the draft of the manuscript. Y-jD and J-hL revised the article and finally approved the study. All authors contributed to the article and approved the submitted version.</p>
</sec>
</body>
<back>
<sec sec-type="funding-information" id="s8">
<title>Funding</title>
<p>This research was supported by the Shanghai Education Science Research of China (No. C2021250) and the Shanghai Normal University Tianhua College.</p>
</sec>
<ack><p>We affirm that the study submitted for publication is original and has not been published other than as an abstract or preprint in any language or format and has not been submitted elsewhere for print or electronic publication consideration. We affirm that each person listed as the author participated in the study in a substantive manner, in accordance with ICMJE authorship guidelines, and is prepared to take public responsibility for it. All authors consent to the investigation of any improprieties that may be alleged regarding the study.</p>
</ack>
<sec sec-type="COI-statement" id="conf1">
<title>Conflict of interest</title>
<p>The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.</p>
</sec>
<sec sec-type="disclaimer" id="s9">
<title>Publisher&#x00027;s note</title>
<p>All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.</p>
</sec>
<sec sec-type="supplementary-material" id="s10">
<title>Supplementary material</title>
<p>The Supplementary Material for this article can be found online at: <ext-link ext-link-type="uri" xlink:href="https://www.frontiersin.org/articles/10.3389/fnins.2023.1221990/full#supplementary-material">https://www.frontiersin.org/articles/10.3389/fnins.2023.1221990/full#supplementary-material</ext-link></p>
<supplementary-material xlink:href="Table_1.DOCX" id="SM1" mimetype="application/vnd.openxmlformats-officedocument.wordprocessingml.document" xmlns:xlink="http://www.w3.org/1999/xlink">
<label>Supplementary material 1</label>
<caption><p>Search strategies.</p></caption> </supplementary-material>
<supplementary-material xlink:href="Image_1.TIF" id="SM2" mimetype="image/tif" xmlns:xlink="http://www.w3.org/1999/xlink">
<label>Supplementary Figure 1</label>
<caption><p>Funnel plot of cognitive decline (CD).</p></caption> </supplementary-material>
<supplementary-material xlink:href="Image_2.TIF" id="SM3" mimetype="image/tif" xmlns:xlink="http://www.w3.org/1999/xlink">
<label>Supplementary Figure 2</label>
<caption><p>Egger&#x00027;s test of cognitive decline (CD).</p></caption> </supplementary-material>
<supplementary-material xlink:href="Image_3.TIF" id="SM4" mimetype="image/tif" xmlns:xlink="http://www.w3.org/1999/xlink">
<label>Supplementary Figure 3</label>
<caption><p>Funnel plot of mild cognitive impairment (MCI).</p></caption> </supplementary-material>
<supplementary-material xlink:href="Image_4.TIF" id="SM5" mimetype="image/tif" xmlns:xlink="http://www.w3.org/1999/xlink">
<label>Supplementary Figure 4</label>
<caption><p>Egger&#x00027;s test of mild cognitive impairment (MCI).</p></caption> </supplementary-material>
<supplementary-material xlink:href="Table_2.DOCX" id="SM6" mimetype="application/vnd.openxmlformats-officedocument.wordprocessingml.document" xmlns:xlink="http://www.w3.org/1999/xlink">
<label>Supplementary Table 1</label>
<caption><p>Quality assessment for inclusion in cohort studies.</p></caption> </supplementary-material>
<supplementary-material xlink:href="Table_3.DOCX" id="SM7" mimetype="application/vnd.openxmlformats-officedocument.wordprocessingml.document" xmlns:xlink="http://www.w3.org/1999/xlink">
<label>Supplementary Table 2</label>
<caption><p>Quality assessment for inclusion in cross-sectional studies.</p></caption> </supplementary-material></sec>
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