The Effects of Exercise For Cognitive Function in

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International Journal of

Environmental Research
and Public Health

Review
The Effects of Exercise for Cognitive Function in Older Adults:
A Systematic Review and Meta-Analysis of Randomized
Controlled Trials
Liya Xu 1,2,† , Hongyi Gu 1,2,† , Xiaowan Cai 1,2 , Yimin Zhang 2,3, *, Xiao Hou 1,2 , Jingjing Yu 2,3
and Tingting Sun 2,3

1 Faculty of Sports and Human Sciences, Beijing Sports University, Beijing 100084, China
2 Key Laboratory of Sports and Physical Health, Ministry of Education, Beijing 100084, China
3 China Institute of Sports and Health, Beijing Sports University, Beijing 100084, China
* Correspondence: ymzhangno1@163.com; Tel.: +86-13641108252
† These authors contributed equally to this work.

Abstract: Background: Physical exercise can slow down the decline of the cognitive function of the
older adults, yet the review evidence is not conclusive. The purpose of this study was to compare the
effects of aerobic and resistance training on cognitive ability. Methods: A computerized literature
search was carried out using PubMed, Cochrane Library, Embase SCOPUS, Web of Science, CNKI
(China National Knowledge Infrastructure), Wanfang, and VIP database to identify relevant articles
from inception through to 1 October 2022. Based on a preliminary search of the database and the
references cited, 10,338 records were identified. For the measured values of the research results,
the standardized mean difference (SMD) and 95% confidence interval (CI) were used to synthesize
the effect size. Results: Finally, 10 studies were included in this meta-analysis. Since the outcome
indicators of each literature are different in evaluating the old cognitive ability, a subgroup analysis
was performed on the included literature. The study of results suggests that aerobic or resistance
training interventions significantly improved cognitive ability in older adults compared with control
interventions with the Mini-Mental State Examination (MD 2.76; 95% CI 2.52 to 3.00), the Montreal
Citation: Xu, L.; Gu, H.; Cai, X.; Cognitive Assessment (MD 2.64; 95% CI 2.33 to 2.94), the Wechsler Adult Intelligence Scale (MD
Zhang, Y.; Hou, X.; Yu, J.; Sun, T. The
2.86; 95% CI 2.25 to 3.47), the Wechsler Memory Scale (MD 9.33; 95% CI 7.12 to 11.54), the Wisconsin
Effects of Exercise for Cognitive
Card Sorting Test (MD 5.31; 95% CI 1.20 to 9.43), the Trail Making Tests (MD −8.94; 95% CI −9.81
Function in Older Adults: A
to −8.07), and the Stroop Color and Word Test (MD −5.20; 95% CI −7.89 to −2.51). Conclusion:
Systematic Review and
Physical exercise improved the cognitive function of the older adults in all mental states. To improve
Meta-Analysis of Randomized
Controlled Trials. Int. J. Environ. Res.
cognitive ability, this meta-analysis recommended that patients perform at least moderate-intensity
Public Health 2023, 20, 1088. https:// aerobic exercise and resistance exercise on as many days as possible in the week to comply with
doi.org/10.3390/ijerph20021088 current exercise guidelines while providing evidence for clinicians.

Academic Editor: Adrian Midgley


Keywords: cognitive ability; exercise interventions; elder; meta-analysis; RCT
Received: 1 December 2022
Revised: 27 December 2022
Accepted: 3 January 2023
Published: 7 January 2023 1. Introduction
The ageing of the population is an issue of widespread concern worldwide. The Report
on World Population Trends (now referred to as the Report) issued at the 51st session of the
United Nations Commission on Population and Development pointed out that the global
Copyright: © 2023 by the authors.
Licensee MDPI, Basel, Switzerland.
population would reach 9.8 billion by 2050. The number of older adults over 65 will exceed
This article is an open access article
1.5 billion, accounting for 16% of the total population. Normal ageing is typically associated
distributed under the terms and with both physical and cognitive decline. Cognitive functioning changes as people grow
conditions of the Creative Commons older. Cognitive function includes memory, language, visual space, execution, calculation,
Attribution (CC BY) license (https:// understanding, and judgment [1]. Most of the older adults also experience a cognitive
creativecommons.org/licenses/by/ decline to varying degrees, which will not only reduce the quality of life but also affect the
4.0/). basic activities of daily living ability, reduce the remaining life expectancy, and increase the

Int. J. Environ. Res. Public Health 2023, 20, 1088. https://doi.org/10.3390/ijerph20021088 https://www.mdpi.com/journal/ijerph
Int. J. Environ. Res. Public Health 2023, 20, 1088 2 of 13

risk of death [2]. Therefore, determining the biological mechanism of cognitive ageing and
seeking preventive measures to offset its harmful effects are the current priorities in clinical
and public health.
It is hypothesized that the neural and vascular adaptations to physical exercise im-
prove cognitive function through promotion of neurogenesis, angiogenesis, synaptic plas-
ticity, decreased proinflammatory processes, and reduced cellular damage due to oxidative
stress. In non-medical therapy, as a low-cost, low-risk, and ready-made intervention,
physical exercise has been widely accepted by the public and medical rehabilitation work-
ers [3]. Regular physical exercise was a critical factor in preventing and managing non-
communicable diseases. Physical exercise is also conducive to mental health, preventing
cognitive decline, depression, and anxiety symptoms, and helps maintain body mass and
overall well-being. Many experiments and clinical studies have shown that physical ex-
ercise can improve the cognitive function of the older adults [4–6]. Regular and active
physical activities of the older adults can promote the maintenance, improvement, or
rehabilitation of biological processes and slow down the decline of age-related cognitive
functions. However, although some experiments have proposed the beneficial effect of
physical activity on healthy older adults, there was no specific conclusion at present [7,8].
The Mini-Mental State Examination (MMSE) is a global clinical psychological, neu-
ropsychological indicator usually used to screen and evaluate the cognitive status of
patients. It can comprehensively, accurately, and quickly reflect the intellectual quality and
cognitive impairment of the subjects [9]. However, there are many scales to evaluate cogni-
tive ability. By incorporating different screening methods, we can more comprehensively
assess the cognitive function of the older adults. In the past few decades, many scientific
research teams have studied the effect of exercise on the cognitive function of the older
adults in randomized controlled trials [10–30]. However, there were contradictions between
the results of these studies, and there was no clear conclusion. This systematic review
and meta-analysis intends to explore the following questions: (i) the effects of exercise
interventions of aerobic and resistance training modes on cognitive ability in the older
adults; and (ii) the effects of exercise on different cognitive task results in the older adults.

2. Materials and Methods


2.1. Data Sources and Searches
This article was followed by the Preferred Reporting Items for Systematic Reviews and
Meta-Analysis (PRISMA) guideline [31]. A literature search used PubMed, Cochrane Li-
brary, Embase SCOPUS, Web of Science, CNKI (China National Knowledge Infrastructure),
Wanfang and VIP database to identify relevant articles from inception through to 1 October
2022. This paper searched three classes of keywords: “cognitive”, “older adults”, and
“exercise”. The first keywords were “cognition”, “executive function”, “cognitive ability”,
“cognitive decline”, and “memory”. The second keywords were “older adults”, “aged”,
“old people”, and “elderly people”. The exercise keywords were “exercise”, “physical
exercise”, “aerobic exercise”, “strength training”, and “intervention”. The search strategy
for PubMed is presented in Table 1.

2.2. Inclusion and Exclusion Criteria


Literature inclusion was based on evidence-based medicine PICOS framework, mainly
considering five factors: participants, intervention measures, control group, research results,
and research design [32]. Inclusion criteria were as follows: (i) participants were over the
aged of 50 years or older; (ii) the treatment groups were intervention consisting of physical
exercise or physical activity; (iii) the control group included routine home care, health
education, or lifestyle maintenance; (iv) the outcomes include the use of any standardized
neuropsychological instrument to measure cognitive ability, and the statistics include:
sample size, mean, and standard deviation; and (v) the studies’ design was strictly limited
to randomized controlled trials (RCTs).
Int. J. Environ. Res. Public Health 2023, 20, 1088 3 of 13

Trials were excluded if they met one of the following exclusion criteria: (i) studies
that do not meet the inclusion criteria; (ii) studies without available data for statistics;
(iii) conference abstract, observational study, dissertation, or letter; and (iv) exclude articles
other than English or Chinese.

Table 1. Database search of PubMed.

# Searches Results
((((“exercise*”[Title/Abstract]) OR (“sport*”[Title/Abstract])) OR
1 (“physical exercise”[Title/Abstract])) OR (“exercise 1,586,474
intervention”[Title/Abstract])) OR (“intervention*”[Title/Abstract])
(((“older adults*”[Title/Abstract]) OR (“aged*”[Title/Abstract])) OR
2 930,566
(“old people”[Title/Abstract])) OR (“elderly people”[Title/Abstract])
(((“cognitive*”[Title/Abstract]) OR (“cognitive ability
3 “[Title/Abstract])) OR (“cognitive function”[Title/Abstract])) OR 443,939
(“cognitive decline”[Title/Abstract])
4 1 and 2 127,165
5 3 and 4 10,645
6 Limit 5 to (English language and humans and “all aged (60 and over)”) 2045

2.3. Study Selection and Data Extraction


The retrieved literature was screened by three researchers (L.X., H.G., and X.C.) in an
independent double-blind way according to the inclusion and exclusion criteria. The first
step was to exclude articles that did not meet the inclusion criteria by reading the title and
abstract of the literature. The second part was to read and screen the remaining documents
in full and determine the final documents to be included. The two researchers (L.X. and
H.G.) independently extracted the literature that met the criteria, including the following
information: author name; publication year of the article; participants’ characteristics
(e.g., age and gender); the number of participants in each group; intervention content;
intervention time; intervention frequency; intervention cycle; and reported outcomes. The
number of participants, average value, and standard deviation (SD) in each group before
and after the intervention training were extracted from the articles included in the analysis.

2.4. Quality Assessment


The two authors (L.X. and H.G.) evaluated the methodological quality of the included
literature, using the Cochrane Collaboration risk bias assessment tools to assess from the
following seven areas [33]: selection bias, performance bias, detection bias, attrition bias,
reporting bias, and any other preferences. Each indicator was judged by low bias risk,
uncertainty, or high bias risk. Any differences arising from the evaluation process shall be
settled by the third arbitrator (X.H.).

2.5. Statistical Analysis


Statistical analyses were undertaken using Review Manager 5.4 (Cochrane Collabora-
tion) and Stata version 12.0 (Stata Corp). Since the measurement scores of the exercise group
and the control group from baseline to the endpoint are continuous variables, Standardized
mean difference (SMD) and 95% confidence intervals (CIs) were calculated according to the
mean, standard deviation and sample number of outcomes indicators of the intervention
group and the control group. The heterogeneity across the studies was evaluated using
the I2 statistic. I2 represents the heterogeneity of the study; when I2 ≤ 25%, it indicated
insignificant heterogeneity. The moderate heterogeneity was assessed when I2 ≤ 50% and
I2 > 25%. When I2 ≤ 75% and I2 > 50%, it indicated high heterogeneity [33]. I2 represents
the heterogeneity of the study; if I2 < 50% or p ≥ 0.05, the fixed effect model is used to
combine the effects; If I2 ≥ 50% and p < 0.05, the random effect model is used for analysis.
If there is heterogeneity, a subgroup analysis of regulatory variables is performed. Vi-
sual analysis of funnel plot symmetry was used to test publication bias [34]. We conducted
it indicated insignificant heterogeneity. The moderate heterogeneity was assessed when
I2 ≤ 50% and I2 > 25%. When I2 ≤ 75% and I2 > 50%, it indicated high heterogeneity [33]. I2
represents the heterogeneity of the study; if I2 < 50% or p ≥ 0.05, the fixed effect model is
used to combine the effects; If I2 ≥ 50% and p < 0.05, the random effect model is used for
analysis.
Int. J. Environ. Res. Public Health 2023, 20, 1088
If there is heterogeneity, a subgroup analysis of regulatory variables is performed. 4 of 13

Visual analysis of funnel plot symmetry was used to test publication bias [34]. We con-
ducted subgroup analysis according to the gender and age of the participants, the type of
subgroup analysis
intervention, andaccording to the
the duration of gender and age oftothe
the intervention participants,
further explore the
the type of interven-
source of hetero-
tion, and the
geneity. Allduration
tests wereof two-tailed,
the intervention
with to further explore
inspection level αthe source
= 0.05; of heterogeneity.
when All p
the bilateral test
tests were
< 0.05, it istwo-tailed,
consideredwith
thatinspection levelisαstatistically
the difference = 0.05; when the bilateral test p < 0.05, it is
significant.
considered that the difference is statistically significant.
3. Results
3. Results
3.1. Search Results
3.1. Search Results
Through searching Chinese and foreign databases, 10,336 articles were preliminarily
Through searching Chinese and foreign databases, 10,336 articles were preliminarily
obtained. Two articles were retrieved manually from other resources. Two independent
obtained. Two articles were retrieved manually from other resources. Two independent
researchers screened 9185 titles and abstracts after eliminating duplicate published arti-
researchers screened 9185 titles and abstracts after eliminating duplicate published articles.
cles. After screening the title and abstract, 9135 research articles were excluded. After fil-
After screening the title and abstract, 9135 research articles were excluded. After filtering
tering titles and abstracts, 9135 articles were excluded. The remaining 50 articles were read
titles and abstracts, 9135 articles were excluded. The remaining 50 articles were read in
in totality, and 21 were included in the final analysis, meeting the requirements of system-
totality, and 21 were included in the final analysis, meeting the requirements of systematic
atic evaluation and meta-analysis. The third reviewer will discuss and decide on any dif-
evaluation and meta-analysis. The third reviewer will discuss and decide on any differences
inferences in thescreening
the literature literature process.
screening process.
The search The search is
procedure procedure
presentedisinpresented
Figure 1. in Figure
1.

Figure1.1.Flowchart
Figure Flowchartrepresenting
representingthe
theselection
selectionprogress.
progress.

3.2.
3.2.Studies
StudiesCharacteristics
Characteristics
AAtotal
total of2121RCT
of RCTresearch
researcharticles
articleswere
wereincluded
includedininthe
themate-analysis
mate-analysis[10–30].
[10–30].All
All
included studies were
included studies were published between 2000 and 2022, including 1414 participants.
between 2000 and 2022, including 1414 participants. The
The subjects
subjects in most
in most studies
studies were
were mixed-gender
mixed-gender groups.
groups. TheThe topics
topics in five
in five studies
studies werewere
only
only
womenwomen [13,18,20,27,28],
[13,18,20,27,28], andand
onlyonly male
male participants
participants wereincluded
were includedininthree
threestudies
stud-
ies [22,23,29]. For exercise types, 12 trials performed physical exercise [10–21], and 9 tests
performed mind–body exercise [22–30]. The duration of exercise intervention varies from
8 to 52 weeks, and each study has its own time and frequency of intervention. Details of
study characteristics are presented in Table 2.
Int. J. Environ. Res. Public Health 2023, 20, 1088 5 of 13

Table 2. Characteristics of the included trials and participants.

Intervention
Mean Age Participants Session Session Outcome
Included Studies Sample Size (N) Intervention Duration
(Years) (M/F) Duration Frequency Measure
(Weeks)
Guadagni et al., 2020 206
65.9 IG = 103; CG = 103 Aerobic 48 60 min 3 times/week MoCA
[15] (101/105)
Song et al., 2019 [19] 75.78 120 (30/90) IG = 60; CG = 60 Aerobic 16 60 min 3 times/week MoCA
Nagamatsu et al., 2012
75.36 58 (0/58) IG = 30; CG = 28 Aerobic 26 60 min 2 times/week TMT
[18]
Ten Brinke et al., 2015
75.78 27 (0/27) IG = 14; CG = 13 Aerobic 26 60 min 2 times/week MMSE; MoCA
[20]
Voss et al., 2013 [21] 64.87 70 (25/45) IG = 35; CG = 35 Aerobic 52 40 min 3 times/week MMSE
Albinet et al., 2010 [11] 70.65 24 (11/13) IG = 12; CG = 12 Aerobic 12 60 min 3 times/week MMSE; WCST
Fabre, 2002 [14] 65.55 16 (3/13) IG = 8; CG = 8 Aerobic 8 60 min 2 times/week WMS
Mortimer et al., 2012 TMT; WAIS;
68 60 (20/40) IG = 30; CG = 30 Aerobic 40 50min 3 times/week
[16] SCWT
Muscari et al., 2010 [17] 69.2 120 (62/58) IG = 60; CG = 60 Aerobic 52 60 min 3 times/week MMSE
Albinet et al., 2016 [10] 66.53 36 (10/26) IG = 19; CG = 17 Aerobic 21 60 min 2 times/week MMSE; SCWT
Antunes et al., 2015 [12] 66.97 46 (46/0) IG = 23; CG = 23 Aerobic 26 60 min 3 times/week WAIS
Karen et al., 2015 [13] 64.58 40 (0/40) IG = 23; CG = 17 Aerobic 26 60 min 3 times/week MMSE; WCST
Lan Li et al., 2021 [26] 70.48 84 (33/51) IG = 42; CG = 42 Resistance 24 30min 5 times/week MMSE; MoCA
Tsai et al., 2015 [29] 71.4 48 (48/0) IG = 24; CG = 24 Resistance 52 60 min 3 times/week MMSE
30 (not
Yoon et al., 2017 [30] 76 IG = 23; CG = 7 Resistance 12 60 min 2 times/week MMSE; MoCA
stated)
Liu-Ambrose et al., 2010 MMSE; TMT;
69.62 101 (0/101) IG = 52; CG = 49 Resistance 52 60 min 2 times/week
[27] SCWT
Liu-Ambrose et al., 2012
69.31 52 (0/52) IG = 15; CG = 17 Resistance 52 60 min 2 times/week MMSE
[28]
Cassilhas et al., 2007
68.08 62 (62/0) IG = 39; CG = 23 Resistance 24 60 min 3 times/week WMS; WAIS
[23]
Kimura et al., 2010 [25] 74.33 119 (49/70) IG = 65; CG = 54 Resistance 12 90 min 2 times/week MMSE
Ansai et al., 2015 [22] 82.7 46 (16/30) IG = 23; CG = 23 Resistance 16 60 min 3 times/week MoCA
2–3
Singh et al., 2014 [24] 70.1 49 (33/16) IG = 22; CG = 27 Resistance 26 75min WMS; WAIS
times/week
M, man; W, woman; IG, intervention group; CG, control group; MMSE, the Mini-Mental State Examination;
MoCA, the Montreal Cognitive Assessment; WAIS, the Wechsler Adult Intelligence Scale; WMS, the Wechsler
Memory Scale; WCST, the Wisconsin Card Sorting Test; TMT, the Trail Making Tests; SCWT, the Stroop Color and
Word Test.

3.3. Quality Evaluation


A summary of the bias risks of all included studies in the meta-analysis is shown in
Figure 2A. Figure 2B shows the deviation risk of bias for self-reported and physiological
measurement of each included study according to the Cochrane risk of bias tool [33].
These 21 studies have relatively high quality, 12 trials reported the generation process of
random sequences, and 5 trials reported the methods used to allocate hiding. Because the
subjects have to carry out exercise intervention and cannot be blinded, the performance
bias assessment in the study was high risk.

3.4. Effects of Exercise on Cognitive Functions


This meta-analysis synthesizes the outcome data of the included studies using the
same outcome indicators. Overall, the meta-analysis included the following cognitive
abilities outcome indicators: the Mini-Mental State Examination (MMSE), the Montreal
Cognitive Assessment (MoCA), the Wechsler Adult Intelligence Scale (WAIS), the Wechsler
memory scale (WMS), the Wisconsin card sorting test (WCST), the Trail Making Tests
(TMT), and the Stroop Color and Word Test (SCWT). The study found that the exercise
intervention methods for the cognitive function of the older adults were mainly divided
into two categories: aerobic and resistance exercise.
Int. J. Environ. Res. Public Health 2023, 20, x FOR PEER REVIEW 6 of 12

random sequences, and 5 trials reported the methods used to allocate hiding. Because
Int. J. Environ. Res. Public Health 2023, 20, 1088 6 of 13
the
subjects have to carry out exercise intervention and cannot be blinded, the performance
bias assessment in the study was high risk.

(A)

(B)
Figure 2. (A).
Figure Risk
2. (A). ofofbias
Risk biassummary; (B) risk
summary; (B) riskofofbias
biasassessments
assessments [10–30].
[10–30].

Twelve
3.4. Effects studieson
of Exercise reported the Functions
Cognitive outcomes of the MMSE scale. Figure 3 shows that the
MMSE score of the exercise group was higher than that of the control group (MD 2.76; 95%
This meta-analysis synthesizes the outcome data of the included studies using the
CI 2.52 to 3.00; p < 0.00001; I2 = 18%), and the heterogeneity between studies was low. Six
same outcome
articles indicators.
reported Overall,
the evaluation the meta-analysis
outcomes included
of the MoCA scale. The the
MoCAfollowing
scores ofcognitive
the
abilities outcome indicators: the Mini-Mental State Examination (MMSE), the
exercise group were higher than that of the control group (MD 2.64; 95% CI 2.33 to 2.9; Montreal
Cognitive Assessment
p < 0.00001; (MoCA),
I2 = 0%). There was no the Wechslerbetween
heterogeneity Adult studies
Intelligence Scale
(Figure 4). Four(WAIS),
studies the
Wechsler memory scale (WMS), the Wisconsin card sorting test (WCST), the Trail Making
Tests (TMT), and the Stroop Color and Word Test (SCWT). The study found that the
Twelve studies reported the outcomes of the MMSE scale. Figure 3 shows that th
MMSE score of the exercise group was higher than that of the control group (MD 2.76
exercise
95% intervention
CI 2.52 to 3.00; methods
p < 0.00001;for theI2 = cognitive
18%), andfunction of the older adults
the heterogeneity between were mainlywas low
studies
divided into two categories: aerobic and resistance exercise.
Six articles reported the evaluation outcomes of the MoCA scale. The MoCA scores of th
Twelve studies reported the outcomes of the MMSE scale. Figure 3 shows that the
exercise group were higher than that of the control group (MD 2.64; 95% CI 2.33 to 2.9;
MMSE
Int. J. Environ. Res. Public Health 2023, 20, 1088 score of the exercise group was higher than that of the control group (MD7 of 2.76;
13
< 0.00001; I2 = 0%). There was2 no heterogeneity between studies (Figure 4). Four studie
95% CI 2.52 to 3.00; p < 0.00001; I = 18%), and the heterogeneity between studies was low.
reported
Six articlesthe outcomes
reported of WAIS.outcomes
the evaluation Compared with
of the the control
MoCA scale. Thegroup, MoCA thescores
WAIS ofscore
the of th
exercise
exercise the group
group increased
were higher significantly
thanCompared (MD
that of thewith 2.86;
control 95% CI 2.25 to 3.47; p < 0.00001; I2 = 39%
reported outcomes of WAIS. the group
control(MD group,2.64;the95%WAIS CI 2.33
scoretoof2.9;
thep
and
exercise thegroup
< 0.00001; heterogeneity
I2 = increased between
0%). Theresignificantly studies
was no heterogeneity
(MD 2.86; was low
between
95% (Figure
CI 2.25 studies 5).(Figure
to 3.47; pThree studies
4).
< 0.00001; Four provided th
I2 =studies
39%),
evaluating outcomes of the WMS scale. Figure 6 shows
and the heterogeneity between studies was low (Figure 5). Three studies providedofthe
reported the outcomes of WAIS. Compared with the control that
group, the
the exercise
WAIS score group’s
the WM
score
exercise
evaluating significantly
group increased
outcomes increased
of the WMS compared
significantlyscale.(MD with
2.86;
Figure theCI
695%
shows control
2.25
thatto group
the3.47; p <(MD
exercise 9.33;I 95%
0.00001;
group’s 2 =WMS
39%),CI 7.12 t
and the
11.54;
score p heterogeneity
significantly I2 =between
< 0.00001;increased 28%), andstudies
compared was the
the with lowcontrol
heterogeneity (Figure 5). Three
between
group (MD studies
studies was
9.33; 95% provided
low.
CI 7.12 the
Two
to studie
evaluating
11.54;
provided outcomes
p < 0.00001;
the I2 = 28%),
evaluating of theoutcomes
WMS
and thescale. Figure
heterogeneity
of the WCST 6 between
shows
scale.that the exercise
studies
Figure 7was
showslow.group’s
Two the
that WMS
studies
WCST scor
score
provided significantly
the evaluating
of the exercise increased
group outcomes compared
was higher of thethanwith
WCST the
thatscale.control
of the Figuregroup
control (MD
7 shows
group 9.33;
that(MD 95%
the WCST CI
5.31; 95%7.12
scoreto
CI 1.20 t
of11.54;
the p < 0.00001;
exercise group I 2 = 28%), and the heterogeneity between studies was low. Two studies
was higher than that of the control group (MD 5.31; 95% CI 1.20 to 9.43;
9.43; p = 0.01; I = 0%). There was no heterogeneity between studies. Three studies provide
2
= 0.01; I2the
pprovided evaluating
= 0%). There was outcomes of the WCSTbetween
no heterogeneity scale. Figure
studies.7 shows
Three that the WCST
studies providedscore
the evaluating outcomes of the TMT scale. As shown in Figure 8, the analysis indicates
of the
the exerciseoutcomes
evaluating group wasofhigher the TMT than that As
scale. of the
showncontrol group 8,
in Figure (MDthe 5.31; 95%indicates,
analysis CI 1.20 to
compared
9.43; p = 0.01;
compared withwith
I2the the
= 0%).
control control
There wasgroup,
group, no a significant
heterogeneity
a significant between
decrease decrease
in TMTstudies. inThree
scores TMT
in the scores
studies
exercise in
providedthe exercis
group
group (MD
the evaluating
(MD −8.94;
−8.94; 95%outcomes 95% CI
CI −9.81oftothe −9.81
−8.07; to −8.07;
TMTp scale. p < 0.00001;
As shown
< 0.00001; 2 I 2 = 30%). Three studies provided th
in Figure
I = 30%). Three 8, the analysis
studies indicates,
provided the
evaluating
evaluating
comparedoutcomes outcomes
with the of ofSCWT
the
control the SCWT
group,scale. scale.
The SCWT
a significant The SCWT
scores
decrease of in scores
the exercise
TMT of the
group
scores inexercise group wer
wereexercise
the lower
lower
than
group thatthan
(MD thatcontrol
of −8.94;
the of
95% theCI control
group togroup
−9.81(MD −5.20;
−8.07; (MD
p < 95% −5.20;
CI −I95%
0.00001; 27.89 CI
to −
= 30%). −7.89
2.51; to
Three =−2.51;
pstudies
0.0002; p =I20.0002;
provided the I2 = 0%
= 0%).
There
There was
evaluatingwas nooutcomes
noheterogeneity of thebetween
heterogeneity between
SCWT studies
scale. (Figure
studies
The SCWT 9). scores
(Figure 9). of the exercise group were
lower than that of the control group (MD −5.20; 95% CI −7.89 to −2.51; p = 0.0002; I2 = 0%).
There was no heterogeneity between studies (Figure 9).

Figure
Figure3.3.3.Forest
Figure Forest
Forest plots
plots
plots of MMSE
ofofMMSE
MMSE scale
scale
scale outcomes
outcomes
outcomes in overall
ininoverall
overall analysis
analysis
analysis [10,11,13,17,20,21,25–30].
[10,11,13,17,20,21,25–30].
[10,11,13,17,20,21,25–30].

Figure4.4.Forest
Figure Forestplots
plotsofofMoCA
MoCAscale
scaleoutcomes
outcomesininoverall
overallanalysis
analysis[15,19,20,22,26,30].
[15,19,20,22,26,30].
Figure 4. Forest plots of MoCA scale outcomes in overall analysis [15,19,20,22,26,30].
Int.
Int. J.J. Environ.
Environ. Res.
Res. Public
Public Health 2023, 20,
Health 2023, 20, 1088
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of 13
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Int. J. Environ. Res. Public Health 2023, 20, x FOR PEER REVIEW 8 of 12
Int. J. Environ. Res. Public Health 2023, 20, x FOR PEER REVIEW 8 of 12

Figure 5. Forest plots of WAIS scale outcomes in overall analysis [12,16,23,24].


Figure 5.
Figure Forest plots
5. Forest plots of
of WAIS
WAIS scale
scale outcomes
outcomes in
in overall
overall analysis
analysis [12,16,23,24].
[12,16,23,24].
Figure 5. Forest plots of WAIS scale outcomes in overall analysis [12,16,23,24].
Figure 5. Forest plots of WAIS scale outcomes in overall analysis [12,16,23,24].
Figure 5. Forest plots of WAIS scale outcomes in overall analysis [12,16,23,24].

Figure 6. Forest plots of WMS scale outcomes in overall analysis [14,23,24].


Figure
Figure 6. Forest plots
Forest plots
6. Forest of
plots of WMS
of WMS scale
WMS scale outcomes
scale outcomes in
outcomes in overall
in overall analysis [14,23,24].
overall analysis
analysis [14,23,24].
Figure 6. [14,23,24].
Figure 6. Forest plots of WMS scale outcomes in overall analysis [14,23,24].
Figure 6. Forest plots of WMS scale outcomes in overall analysis [14,23,24].

Figure 7. Forest plots of WCST scale outcomes in overall analysis [11,13].


Figure 7. Forest plots of WCST scale outcomes in overall analysis [11,13].
Figure
Figure 7. Forest
Forest plots
plots of
of WCST scale outcomes in overall analysis [11,13].
Figure
Figure 7.
7. Forest
Forest plots
plots of
of WCST
WCST scale
scale outcomes
outcomes in
in overall
overall analysis
analysis [11,13].
[11,13].

Figure 8. Forest plots of TMT scale outcomes in overall analysis [16,18,27].


Figure 8. Forest plots of TMT scale outcomes in overall analysis [16,18,27].
Figure 8. Forest plots of TMT scale outcomes in overall analysis [16,18,27].
Figure
Figure 8.
Figure 8. Forest
8. Forest plots
Forest plots of
of TMT
TMT scale
scale outcomes
outcomes in
in overall
overall analysis
analysis [16,18,27].
[16,18,27].

Figure 9. Forest plots of SCWT scale outcomes in overall analysis [11,13].


Figure 9. Forest plots of SCWT scale outcomes in overall analysis [11,13].
Figure 9. Forest plots of SCWT scale outcomes in overall analysis [11,13].
Figure 9.
9. Forest
Forest plots
3.5. Publication
Figure Bias of
plots of SCWT
SCWT scale
scale outcomes
outcomes in
in overall
overall analysis [11,13].
analysis [11,13].
3.5. Publication Bias
3.5.
3.5. Publication
Publication Bias
A visual inspection
Bias of the funnel plots for seven different outcomes (Figure 10) indi-
3.5. Publication
Publication
Ano
visual Bias
Bias
inspection offor
thethe
funnel plotsability
for seven different outcomes (Figure 10) indi-
catedA publication
visual bias
inspection of the cognitive
funnel plots for of the
seven older adults.
different outcomes (Figure 10) indi-
A
catedAnovisual inspection
inspection
publication
visual of
of the
the
biasoffor
inspection the
the funnel
funnel plots
plots
cognitive
funnel for
for seven
seven
ability
plotsability
for seven different
different
of the outcomes
outcomes (Figure
older adults.
different outcomes (Figure 10)
(Figure 10) indi-
10) indi-
indi-
cated
cated no
no publication
publication bias
bias for
for the
the cognitive
cognitive of the older adults.
ability of the older adults.
cated no publication bias for the cognitive ability of the older adults.
Int. J. Environ. Res. Public Health 2023, 20, x FOR PEER REVIEW 9 of 12
Int. J. Environ. Res. Public Health 2023, 20, 1088 9 of 13

Figure 10. Funnel plot assessing the publication bias.


Figure 10. Funnel plot assessing the publication bias.
4. Discussion
4. Discussion
This study explored the intervention effect of exercise on the cognitive function of the
This study
older adults from explored the
the perspective intervention effect
of evidence-based of exercise
medicine. The on the cognitive
results showed that function of
exercise the older
could adults from
effectively thethe
delay perspective ofthe
decline of evidence-based medicine.
cognitive function Theolder
of the results showed that
adults.
Accordingexercise could effectively
to 21 eligible delay theand
trials, we extracted decline of the
analyzed cognitive
cognitive function
ability of the
(MMSE, older adults.
MoCA,
WAIS, WMS, WCST, TMT, SCWT scales) outcomes to evaluate the cognitive function (MMSE,
According to 21 eligible trials, we extracted and analyzed cognitive ability
MoCA,
change after WAIS,interventions.
exercise WMS, WCST, TMT, SCWT
The key scales)from
finding outcomes to evaluate
this study is thatthe cognitive func-
physical
exercise tion change after
interventions exercise improve
effectively interventions. The key
cognitive finding
function from
in the this study
elder, is that
regardless ofphysical
exercise interventions effectively improve cognitive function in the elder, regardless of
mental status.
Themental
overallstatus.
analyses suggest evident improvements in exercise on cognitive ability in
the elder. The study found that the scores of the cognitive ability assessment scale (MMSE,
Int. J. Environ. Res. Public Health 2023, 20, 1088 10 of 13

MoCA, WAIS, WMS, and WCST) were significantly increased in the low heterogeneity and
non-heterogeneity intervention groups. Specifically, exercise positively affected cognitive
ability by reducing scores on TMT and SCWT scales.
Studies that included aerobic or resistance training in traditional exercise patterns
showed similar results. Some studies [35] have found that changes in carotid artery
elasticity and imbalance of vasoconstriction and relaxation function can aggravate the
degree of cognitive ability damage. These changes will significantly affect the body’s
ability to supply blood and oxygen to brain tissue, causing a large amount of oxygen
free radicals to accumulate and damage brain tissue. Therefore, exercise can improve
cardiovascular function, increase cerebral blood flow and oxygen supply capacity, give
brain tissue cells more nutrition, help maintain brain function, and, thus, delay or reverse
the neurodegenerative process and disease tracking.
Our study suggests that aerobic exercise benefits older adults’ cognitive functioning.
Studies have investigated the effects of two short-term exercise intervention plans on
various outcome parameters and executive ability of heart rate variability (HRV) in the
older adults by Albinet et al. [11]. The results emphasize that aerobic exercise intervention
played an essential role in cardio cerebral vascular protection and show a direct relationship
between exercise, HRV, and cognition in the older adults. In addition, some studies have
also concluded that specific aerobic intervention can improve the cognitive function of the
older adults to varying degrees [10,12–21].
This study suggests that resistance training may be essential in improving cognitive
function in older adults [36]. Resistance exercise can increase the operation of muscle
pumps by squeezing peripheral blood vessels, which can increase the cardiac output per
stroke, thus increasing cerebral perfusion. Liu-Ambrose et al. compared the effects of
different resistance training models on the cognitive function of the older adults [27]. The
results showed that resistance training benefited the older women’s selective attention and
the executive effect of cognitive ability. This indicates that the intervention of resistance
movement has a particularly significant impact on the cognitive function of these older
people [22–26,28–30].
Previous studies believed that exercise positively impacts the cognitive ability of
the older adults, improving memory and inhibition control functions. Exercise is an
effective means to treat and intervene in cognitive impairment in the older adults, consistent
with the previous review [35,37]. Some studies showed that exercise intervention could
improve the cognitive function of the older adults, providing strong evidence for exercise
as an effective non-drug intervention. Still, the method of exercise needs to be designed
according to the differences between different individuals, which was the main reason
for the differences in many research results. In addition, most of the studies were aimed
at patients’ physical indicators and cognitive ability, and there were few studies on the
mechanism of brain action.
This paper summarizes the intervention of different intervention methods, different
from other studies that outline a single sports event. The utility of different periodic and
types of sports was more straightforward, which provided a reference for future research
and practical application. This paper summarizes the beneficial evidence of aerobic exercise
and resistance exercise in improving the cognitive ability of the older adults points out the
positive effect of aerobic exercise and resistance movement on improving mild cognitive
impairment and emphasizes that we must follow the scientific and safe principles, adopt
reasonable exercise methods, improve the cognitive ability of the older adults through
regular scientific exercise, improve the body ability and cardiopulmonary function, and
provide conditions for the older adults to maintain continuous training.
This study was carried out following the PRISMA statement list, but there were still
some shortcomings and limitations. First, the search scope for the literature does not include
unpublished literature, and some literature is not included due to incomplete outcome
index data, which may affect the comprehensiveness of the data to some extent. Meanwhile,
the sample size of the meta-analysis fit in the study is small, which may also reduce the
Int. J. Environ. Res. Public Health 2023, 20, 1088 11 of 13

reliability of the analysis results. Finally, although two researchers used an independent
double-blind method to evaluate the quality of the included literature, they only used
the “Cochrane Risk Bias Tool” for evaluation. Due to subjective judgment errors, specific
evaluation errors may be caused. Therefore, it is recommended to add other judgment
criteria to minimize personal evaluation error.

5. Conclusions
This systematic review and meta-analysis demonstrate that regular exercise benefits
older adults’ cognitive function. Exercise could be used as a supplementary therapy to
treat the cognitive decline of the older adults.

Author Contributions: Designed the study and wrote the protocol, L.X., H.G., X.C., X.H. and
Y.Z.; Independent screening and data extraction, L.X., H.G. and X.C.; Quality scoring, J.Y. and T.S.;
Statistical analysis and wrote the first draft, L.X. and H.G.; Revised the manuscript, X.H. and Y.Z. All
the authors made significant contributions to the final manuscript and approved its publication. All
authors have read and agreed to the published version of the manuscript.
Funding: This work was supported by “the National Key Research and Development Program of
China” (2020YFC2006701).
Institutional Review Board Statement: Not applicable.
Informed Consent Statement: Not applicable.
Data Availability Statement: The data presented in this study are openly available in the studies
referenced in the figures. The individual data in each can be seen in the original manuscripts.
Conflicts of Interest: The authors declare no conflict of interest.

References
1. Colcombe, S.J.; Erickson, K.I.; Raz, N.; Webb, A.G.; Cohen, N.J.; McAuley, E.; Kramer, A.F. Aerobic fitness reduces brain tissue
loss in aging humans. J. Gerontol. Ser. A Biol. Sci. Med. Sci. 2003, 58, 176–180. [CrossRef]
2. Van Dam, P.S.; Aleman, A. Insulin-like growth factor-I, cognition and brain aging. Eur. J. Pharmacol. 2004, 490, 87–95. [CrossRef]
3. Angevaren, M.; Aufdemkampe, G.; Verhaar, H.J.; Aleman, A.; Vanhees, L. Physical activity and enhanced fitness to improve
cognitive function in older people without known cognitive impairment. Cochrane Database Syst. Rev. 2008, 3, 538–541.
4. Kronenberg, G.; Bick-Sander, A.; Bunk, E.; Wolf, C.; Ehninger, D.; Kempermann, G. Physical exercise prevents age-related decline
in precursor cell activity in the mouse dentate gyrus. Neurobiol. Aging 2006, 27, 1505–1513. [CrossRef] [PubMed]
5. Van Uffelen, J.G.; Chin, A.P.M.J.; Hopman-Rock, M.; Van Mechelen, W. The effects of exercise on cognition in older adults with
and without cognitive decline: A systematic review. Clin. J. Sport Med. Off. J. Can. Acad. Sport Med. 2008, 18, 486–500. [CrossRef]
[PubMed]
6. Pedroli, E.; Greci, L.; Colombo, D.; Serino, S.; Cipresso, P.; Arlati, S.; Mondellini, M.; Boilini, L.; Giussani, V.; Goulene, K.; et al.
Characteristics, Usability, and Users Experience of a System Combining Cognitive and Physical Therapy in a Virtual Environment:
Positive Bike. Sensors 2018, 18, 2343. [CrossRef]
7. Kramer, A.F.; Hahn, S.; Cohen, N.J.; Banich, M.T.; McAuley, E.; Harrison, C.R.; Chason, J.; Vakil, E.; Bardell, L.; Boileau, R.A.
Ageing, fitness and neurocognitive function. Nature 1999, 400, 418–429. [CrossRef]
8. Colcombe, S.; Kramer, A.F. Fitness effects on the cognitive function of older adults: A meta-analytic study. Psychol. Sci. 2003, 14,
125–130. [CrossRef]
9. Mitrushina, M.; Satz, P. Reliability and validity of the Mini-Mental State Exam in neurologically intact elderly. J. Clin. Psychol.
1991, 47, 537–543. [CrossRef] [PubMed]
10. Albinet, C.T.; Abou-Dest, A.; André, N.; Audiffren, M. Executive functions improvement following a 5-month aquaerobics
program in older adults: Role of cardiac vagal control in inhibition performance. Biol. Psychol. 2016, 115, 69–77. [CrossRef]
11. Albinet, C.T.; Boucard, G.; Bouquet, C.A.; Audiffren, M. Increased heart rate variability and executive performance after aerobic
training in the elderly. Eur. J. Appl. Physiol. 2010, 109, 617–624. [CrossRef] [PubMed]
12. Antunes, H.K.; De Mello, M.T.; Santos-Galduróz, R.F.; Galduróz, J.C.; Lemos, V.A.; Tufik, S.; Bueno, O.F. Effects of a physical
fitness program on memory and blood viscosity in sedentary elderly men. Braz. J. Med. Biol. Res. Rev. Bras. Pesqui. Med. Biol.
2015, 48, 805–812. [CrossRef]
Int. J. Environ. Res. Public Health 2023, 20, 1088 12 of 13

13. Antunes, H.K.; Santos-Galduroz, R.F.; De Aquino Lemos, V.; Bueno, O.F.; Rzezak, P.; De Santana, M.G.; De Mello, M.T. The
influence of physical exercise and leisure activity on neuropsychological functioning in older adults. Age 2015, 37, 981–995.
[CrossRef] [PubMed]
14. Fabre, C.; Chamari, K.; Mucci, P.; Massé-Biron, J.; Préfaut, C. Improvement of cognitive function by mental and/or individualized
aerobic training in healthy elderly subjects. Int. J. Sport. Med. 2002, 23, 415–421. [CrossRef] [PubMed]
15. Guadagni, V.; Drogos, L.L.; Tyndall, A.V.; Davenport, M.H.; Anderson, T.J.; Eskes, G.A.; Longman, R.S.; Hill, M.D.; Hogan, D.B.;
Poulin, M.J. Aerobic exercise improves cognition and cerebrovascular regulation in older adults. Neurology 2020, 94, 2245–2257.
[CrossRef]
16. Mortimer, J.A.; Ding, D.; Borenstein, A.R.; DeCarli, C.; Guo, Q.; Wu, Y.; Zhao, Q.; Chu, S. Changes in brain volume and cognition in
a randomized trial of exercise and social interaction in a community-based sample of non-demented Chinese elders. J. Alzheimer’s
Dis. JAD 2012, 30, 757–766. [CrossRef]
17. Muscari, A.; Giannoni, C.; Pierpaoli, L.; Berzigotti, A.; Maietta, P.; Foschi, E.; Ravaioli, C.; Poggiopollini, G.; Bianchi, G.; Magalotti,
D. Chronic endurance exercise training prevents aging-related cognitive decline in healthy older adults: A randomized controlled
trial. Int. J. Geriatr. Psychiatry 2010, 25, 1055–1064. [CrossRef]
18. Nagamatsu, L.S.; Handy, T.C.; Hsu, C.L.; Voss, M.; Liu-Ambrose, T. Resistance training promotes cognitive and functional brain
plasticity in seniors with probable mild cognitive impairment. Arch. Intern. Med. 2012, 172, 666–678. [CrossRef]
19. Song, D.; Yu, D.S.F. Effects of a moderate-intensity aerobic exercise programme on the cognitive function and quality of life of
community-dwelling elderly people with mild cognitive impairment: A randomised controlled trial. Int. J. Nurs. Stud. 2019, 93,
97–105. [CrossRef]
20. Ten Brinke, L.F.; Bolandzadeh, N.; Nagamatsu, L.S.; Hsu, C.L.; Davis, J.C.; Miran-Khan, K.; Liu-Ambrose, T. Aerobic exercise
increases hippocampal volume in older women with probable mild cognitive impairment: A 6-month randomised controlled
trial. Br. J. Sport. Med. 2015, 49, 248–254. [CrossRef]
21. Voss, M.W.; Heo, S.; Prakash, R.S.; Erickson, K.I.; Alves, H.; Chaddock, L.; Szabo, A.N.; Mailey, E.L.; Wójcicki, T.R.; White, S.M.
The influence of aerobic fitness on cerebral white matter integrity and cognitive function in older adults: Results of a one-year
exercise intervention. Hum. Brain Mapp. 2013, 34, 2972–2985. [CrossRef]
22. Ansai, J.H.; Rebelatto, J.R. Effect of two physical exercise protocols on cognition and depressive symptoms in oldest-old people:
A randomized controlled trial. Geriatr. Gerontol. Int. 2015, 15, 1127–1134. [CrossRef]
23. Cassilhas, R.C.; Viana, V.A.; Grassmann, V.; Santos, R.T.; Santos, R.F.; Tufik, S.; Mello, M.T. The impact of resistance exercise on
the cognitive function of the elderly. Med. Sci. Sport. Exerc. 2007, 39, 1401–1407. [CrossRef] [PubMed]
24. Fiatarone Singh, M.A.; Gates, N.; Saigal, N.; Wilson, G.C.; Meiklejohn, J.; Brodaty, H.; Wen, W.; Singh, N.; Baune, B.T.; Suo, C.
The Study of Mental and Resistance Training (SMART) study—Resistance training and/or cognitive training in mild cognitive
impairment: A randomized, double-blind, double-sham controlled trial. J. Am. Med. Dir. Assoc. 2014, 15, 873–880. [CrossRef]
25. Kimura, K.; Obuchi, S.; Arai, T.; Nagasawa, H.; Shiba, Y.; Watanabe, S.; Kojima, M. The influence of short-term strength training
on health-related quality of life and executive cognitive function. J. Physiol. Anthropol. 2010, 29, 95–101. [CrossRef] [PubMed]
26. Li, L.; Liu, M.; Zeng, H.; Pan, L. Multi-component exercise training improves the physical and cognitive function of the elderly
with mild cognitive impairment: A six-month randomized controlled trial. Ann. Palliat. Med. 2021, 10, 8919–8929. [CrossRef]
[PubMed]
27. Liu-Ambrose, T.; Nagamatsu, L.S.; Graf, P.; Beattie, B.L.; Ashe, M.C.; Handy, T.C. Resistance training and executive functions: A
12-month randomized controlled trial. Arch. Intern. Med. 2010, 170, 170–178. [CrossRef]
28. Liu-Ambrose, T.; Nagamatsu, L.S.; Voss, M.W.; Khan, K.M.; Handy, T.C. Resistance training and functional plasticity of the aging
brain: A 12-month randomized controlled trial. Neurobiol. Aging 2012, 33, 1690–1698. [CrossRef]
29. Tsai, C.L.; Wang, C.H.; Pan, C.Y.; Chen, F.C. The effects of long-term resistance exercise on the relationship between neurocognitive
performance and GH, IGF-1, and homocysteine levels in the elderly. Front. Behav. Neurosci. 2015, 9, 23–33. [CrossRef]
30. Yoon, D.H.; Kang, D.; Kim, H.J.; Kim, J.S.; Song, H.S.; Song, W. Effect of elastic band-based high-speed power training on cognitive
function, physical performance and muscle strength in older women with mild cognitive impairment. Geriatr. Gerontol. Int. 2017,
17, 765–772. [CrossRef]
31. Page, M.J.; McKenzie, J.E.; Bossuyt, P.M.; Boutron, I.; Hoffmann, T.C.; Mulrow, C.D.; Shamseer, L.; Tetzlaff, J.M.; Akl, E.A.;
Brennan, S.E. The PRISMA 2020 statement: An updated guideline for reporting systematic reviews. BMJ 2021, 372, 71–80.
[CrossRef]
32. Methley, A.M.; Campbell, S.; Chew-Graham, C.; McNally, R.; Cheraghi-Sohi, S. PICO, PICOS and SPIDER: A comparison study
of specificity and sensitivity in three search tools for qualitative systematic reviews. BMC Health Serv. Res. 2014, 14, 579–586.
[CrossRef] [PubMed]
33. Higgins, J.P.; Altman, D.G.; Gøtzsche, P.C.; Jüni, P.; Moher, D.; Oxman, A.D.; Savovic, J.; Schulz, K.F.; Weeks, L.; Sterne, J.A. The
Cochrane Collaboration’s tool for assessing risk of bias in randomised trials. BMJ 2011, 343, 5928–5936. [CrossRef] [PubMed]
34. Egger, M.; Davey Smith, G.; Schneider, M.; Minder, C. Bias in meta-analysis detected by a simple, graphical test. BMJ 1997, 315,
629–634. [CrossRef]
Int. J. Environ. Res. Public Health 2023, 20, 1088 13 of 13

35. Northey, J.M.; Cherbuin, N.; Pumpa, K.L.; Smee, D.J.; Rattray, B. Exercise interventions for cognitive function in adults older than
50: A systematic review with meta-analysis. Br. J. Sport. Med. 2018, 52, 154–160. [CrossRef] [PubMed]
36. Gates, N.; Fiatarone Singh, M.A.; Sachdev, P.S.; Valenzuela, M. The effect of exercise training on cognitive function in older adults
with mild cognitive impairment: A meta-analysis of randomized controlled trials. Am. J. Geriatr. Psychiatry Off. J. Am. Assoc.
Geriatr. Psychiatry 2013, 21, 1086–1097. [CrossRef]
37. Liu, L.; Jia, L.; Jian, P.; Zhou, Y.; Zhou, J.; Wu, F.; Tang, Y. The Effects of Benzodiazepine Use and Abuse on Cognition in the Elders:
A Systematic Review and Meta-Analysis of Comparative Studies. Front. Psychiatry 2020, 11, 755–768. [CrossRef]

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