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. 2023 Jan 10:14:1077732.
doi: 10.3389/fnagi.2022.1077732. eCollection 2022.

Effect of exercise on cognitive function and synaptic plasticity in Alzheimer's disease models: A systematic review and meta-analysis

Linlin Guo  1 , Xinxin Yang  1 , Yuanyuan Zhang  1 , Xinyi Xu  1   2 , Yan Li  1   3   4
Affiliations

Effect of exercise on cognitive function and synaptic plasticity in Alzheimer's disease models: A systematic review and meta-analysis

Linlin Guo et al. Front Aging Neurosci. .

Abstract

Introduction: Cognitive decline is a central manifestation of Alzheimer's disease (AD), and its process is inseparable from changes in synaptic plasticity. The aim of this review was to summarize and evaluate the effectiveness of exercise on cognitive function and synaptic plasticity in AD animal models.

Materials and methods: Eligible studies were searched from PubMed, MEDLINE, EMBASE, Web of Science, and Cochrane Library from April to May 2022. The risk of bias was evaluated by Systematic Review Centre for Laboratory Animal Experimentation (SYRCLE). The Morris water maze (MWM) test and synaptic plasticity were considered outcome measures. Data were analyzed using random-effects meta-analyses using the software Stata. Heterogeneity was examined by using I2 test. Sensitivity analysis and publication bias were also assessed.

Results: A total of 20 randomized controlled studies were eligible for study inclusion. Compared with controls, exercise decreased escape latency (SMD = -0.86, 95% CI: -1.21 to -0.50, P < 0.001), increased platform crossover numbers (SMD = 1.34, 95% CI: 0.57-2.11, P = 0.001) and time in the target quadrant (SMD = 1.65, 95% CI: 0.95-2.36, P < 0.001) and the expression of PSD95 (SMD = 0.73, 95% CI: 0.25-1.21, P = 0.003) in AD animals. The results of the subgroup analysis showed that exercise before AD had a greater effect on escape latency (SMD = -0.88, 95% CI: -1.25 to -0.52, P < 0.001), platform crossover numbers (SMD = 1.71, 95% CI: 1.23-2.18, P < 0.001), time in the target quadrant (SMD = 2.03, 95% CI: 1.19-2.87, P < 0.001) and the expression of PSD95 (SMD = 0.94, 95% CI: 0.19-1.69, P = 0.014) than exercise after AD. The results of the subgroup analysis also showed that treadmill running might be an appropriate exercise type.

Conclusion: Our findings suggested that exercise had a potential effect on improving cognitive function and synaptic plasticity. It can play a better neuroprotective role before AD.

Systematic review registration: PROSPERO, identifier: CRD42022328438.

Keywords: Alzheimer's disease; animal; cognitive function; exercise; synaptic plasticity.

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Conflict of interest statement

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.

Figures

Figure 1
Figure 1
The flow diagram of the study selection process.
Figure 2
Figure 2
Forest plots showing the effect of exercise on cognitive function in AD models. (A) The effect of exercise on the escape latency of MWM. (B) The effect of exercise on the number of platform crossings of MWM. (C) The effect of exercise on the time in the target quadrant of MWM.
Figure 3
Figure 3
Forest plot showing the effect of exercise on the expression of PSD95 in AD models.
Figure 4
Figure 4
Subgroup analysis of exercise type on cognitive function in AD models. (A) Subgroup analysis of exercise type on the escape latency of MWM. (B) Subgroup analysis of exercise type on the number of platform crossings of MWM. (C) Subgroup analysis of exercise type on the time in the target quadrant of MWM.
Figure 5
Figure 5
Subgroup analysis of exercise type on the expression of PSD95 in AD models.
Figure 6
Figure 6
Funnel plots showing the effect of exercise on cognitive function and synaptic plasticity in AD models. (A) Funnel plot for the effect of exercise on the escape latency of MWM. (B) Funnel plot for the effect of exercise on the number of platform crossings of MWM. (C) Funnel plot for the effect of exercise on the time in the target quadrant of MWM. (D) Funnel plot for the effect of exercise on the expression of PSD95.
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