Physical activity as a protective factor for dementia and Alzheimer's disease: systematic review, meta-analysis and quality assessment of cohort and case-control studies

Objective Physical activity (PA) is associated with a decreased incidence of dementia, but much of the evidence comes from short follow-ups prone to reverse causation. This meta-analysis investigates the effect of study length on the association. Design A systematic review and meta-analysis. Pooled effect sizes, dose-response analysis and funnel plots were used to synthesise the results. Data sources CINAHL (last search 19 October 2021), PsycInfo, Scopus, PubMed, Web of Science (21 October 2021) and SPORTDiscus (26 October 2021). Eligibility criteria Studies of adults with a prospective follow-up of at least 1 year, a valid cognitive measure or cohort in mid-life at baseline and an estimate of the association between baseline PA and follow-up all-cause dementia, Alzheimer's disease or vascular dementia were included (n=58). Results PA was associated with a decreased risk of all-cause dementia (pooled relative risk 0.80, 95% CI 0.77 to 0.84, n=257 983), Alzheimer's disease (0.86, 95% CI 0.80 to 0.93, n=128 261) and vascular dementia (0.79, 95% CI 0.66 to 0.95, n=33 870), even in longer follow-ups (>= 20 years) for all-cause dementia and Alzheimer's disease. Neither baseline age, follow-up length nor study quality significantly moderated the associations. Dose-response meta-analyses revealed significant linear, spline and quadratic trends within estimates for all-cause dementia incidence, but only a significant spline trend for Alzheimer's disease. Funnel plots showed possible publication bias for all-cause dementia and Alzheimer's disease. Conclusion PA was associated with lower incidence of all-cause dementia and Alzheimer's disease, even in longer follow-ups, supporting PA as a modifiable protective lifestyle factor, even after reducing the effects of reverse causation.