A dose-response meta-analysis of physical activity and the risk of alzheimer's disease in prospective studies.

Background: 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.

Methods: 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.

Results: 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.

Conclusions: 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.