A dose-response meta-analysis of physical activity and the risk of alzheimer's disease in prospective studies.
Level 3 - non-randomized controlled study
Systematic review and meta-analysis of prospective observational cohort studies
PubMed 40053161 · doi:10.1007/s00415-025-12960-1
What was done
Systematic review and dose-response meta-analysis of prospective studies searched across PubMed, Embase, Web of Science, and Cochrane Library up to November 1, 2024. English-language studies reporting multivariate-adjusted effect estimates for physical activity and incident Alzheimer's disease were pooled using random-effects models, alongside linear and non-linear dose-response analyses, subgroup analyses, sensitivity analyses, and multifactorial meta-regression.
What was found
The primary analysis included 29 studies (plus 3 supplemental studies) encompassing 1,453,561 participants and 68,497 diagnosed Alzheimer's disease cases. High-intensity physical activity was associated with a 26% reduction in Alzheimer's risk (HR 0.74, 95% CI 0.67-0.83). Linear dose-response analysis demonstrated a 15% risk reduction per 10 MET-h/week increase in physical activity. Subgroup analyses showed stronger associations in individuals with BMI under 25 (HR 0.65, 95% CI 0.52-0.82), individuals aged 75 years or older (HR 0.57, 95% CI 0.48-0.67), and non-APOE e4 carriers (HR 0.72, 95% CI 0.55-0.93). Meta-regression did not identify specific drivers of between-study heterogeneity.
Why it matters
This review provides large-scale epidemiological quantification showing a dose-dependent inverse relationship between physical activity volume and incident Alzheimer's disease, highlighting differential risk reductions across age, weight, and genetic subgroups.
Limits
All included studies were observational cohorts, leaving potential for residual confounding and reverse causation where prodromal cognitive decline reduces activity. Methods for measuring physical activity and diagnosing Alzheimer's disease varied, non-English studies were excluded, and multifactorial meta-regression failed to explain observed heterogeneity.
Cited by
- supports Epidemiological research shows that exercise and physical activity are protective against Alzheimer's disease risk.