Jiang Yanjie, Jin Zhihui, Wang Hanyu, He Xingyi, Fu Rui, Yu Xinglang, Fu Qinwei, Tian Jing, Li Wenshan, Zhu Xiaoyu, Zhang Shipeng, Lu Yan
Nanjing Hospital of Chinese Medicine Affiliated to Nanjing University of Chinese Medicine, No.157 Daming Road, Nanjing, 210022, China.
Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu University of Traditional Chinese Medicine, Chengdu, 610072, China.
J Neurol. 2025 Mar 7;272(4):256. doi: 10.1007/s00415-025-12960-1.
Alzheimer's disease (AD) has become an increasing global health challenge, particularly with the accelerated aging of the population. Therefore, preventive research targeting AD has become especially important. In recent years, physical activity (PA), as a potential non-pharmacological intervention, has garnered increasing attention from researchers. The aim of this study was to evaluate the effect of PA on AD risk through systematic review and meta-analysis and to further explore its potential preventive benefits.
The literature search for this study encompassed PubMed, Embase, Web of Science, and the Cochrane Library databases, covering publications from their inception until November 1, 2024. Only English-language publications were included. Stratified analyses were conducted to explore the relationship between PA and AD risk by combining multivariate-adjusted effect estimates using random-effects models, along with subgroup analyses, sensitivity analyses, multifactorial meta-regression, and dose-response analyses to comprehensively assess the association between PA and the risk of AD.
Ultimately, 29 studies were included in the primary analysis, along with 3 additional studies for supplemental analyses, involving 1,453,561 participants, of whom 68,497 were diagnosed with AD. The results indicated that high-intensity PA significantly reduced the risk of AD by 26% (Hazard ratio [HR] = 0.74, 95% CI 0.67-0.83). Additionally, dose-response analyses revealed both linear and nonlinear associations, with linear dose-response results indicating a 15% reduction in AD risk for every 10 MET-h/wk increase in PA. Subgroup analyses indicated that the protective effect of PA was more pronounced in the non-obese population (BMI < 25) (HR = 0.65, 95% CI, 0.52-0.82), in individuals aged 75 years or older (HR = 0.57, 95% CI 0.48-0.67), and in non-APOE ε4 gene carriers (HR = 0.72, 95% CI 0.55-0.93), who exhibited greater protection. To explore the sources of heterogeneity among the included studies, a multifactorial meta-regression analysis was performed, which did not significantly explain the heterogeneity of the primary outcomes. Moreover, the robustness of the pooled results was confirmed through supplemental meta-analysis, subgroup analysis, and sensitivity analysis.
The results of this study support the potential of PA in reducing the risk of AD, particularly in non-obese populations, older age groups, and non-APOE ε4 gene carriers. PA holds significant potential in public health as a feasible and low-cost non-pharmacological intervention strategy.
阿尔茨海默病（AD）已成为日益严峻的全球健康挑战，尤其是在人口加速老龄化的背景下。因此，针对AD的预防研究变得尤为重要。近年来，体育活动（PA）作为一种潜在的非药物干预措施，越来越受到研究人员的关注。本研究旨在通过系统评价和荟萃分析评估PA对AD风险的影响，并进一步探索其潜在的预防益处。
本研究的文献检索涵盖了PubMed、Embase、Web of Science和Cochrane图书馆数据库，涵盖从数据库建立至2024年11月1日的出版物。仅纳入英文出版物。通过使用随机效应模型合并多变量调整后的效应估计值进行分层分析，以探讨PA与AD风险之间的关系，同时进行亚组分析、敏感性分析、多因素荟萃回归和剂量反应分析，以全面评估PA与AD风险之间的关联。
最终，29项研究纳入主要分析，另有3项研究用于补充分析，涉及1,453,561名参与者，其中68,497人被诊断为AD。结果表明，高强度PA可使AD风险显著降低26%（风险比[HR]=0.74，95%CI 0.67-0.83）。此外，剂量反应分析显示了线性和非线性关联，线性剂量反应结果表明，PA每增加10 MET-h/周，AD风险降低15%。亚组分析表明，PA的保护作用在非肥胖人群（BMI<25）（HR=0.65，95%CI，0.52-0.82）、75岁及以上个体（HR=0.57，95%CI 0.48-0.67）和非APOE ε4基因携带者（HR=0.72，95%CI 0.55-0.93）中更为明显，这些人群表现出更大的保护作用。为了探究纳入研究之间异质性的来源，进行了多因素荟萃回归分析，但该分析并未显著解释主要结局的异质性。此外，通过补充荟萃分析、亚组分析和敏感性分析证实了汇总结果的稳健性。
本研究结果支持PA在降低AD风险方面的潜力，尤其是在非肥胖人群、老年人群和非APOE ε4基因携带者中。作为一种可行且低成本的非药物干预策略，PA在公共卫生方面具有巨大潜力。
