Causal Effect of Physical Activity on Reducing the Risk of Dementia: Instrumental Variable Analysis Using 2013-16 Cohort Data from JAGES

Background: To examine the causal effect of physical activity on the risk of dementia, we conducted competing-risks survival analysis using the instrumental variable (IV) method. Residency in a snowy area was treated as an IV for frequency of physical activity. We obtained prospective cohort data from the Japan Gerontological Evaluation Study (JAGES). Methods: The baseline study was conducted in 23 municipalities in Japan from October to December 2013. Participants included 97,821 individuals aged 65 or older who completed the JAGES and were physically and cognitively independent at baseline. The incidence of dementia was ascertained by linking to registries of public long-term care insurance through 2016. During the mean follow-up of 3·2 years, we ascertained the incidence of dementia in 4,633 cases (4·7%). Findings: Through IV estimation, we found protective effects of physical activity at various levels of intensity on the risk of dementia: vigorous intensity (sub-distribution hazard ratio 0·62, 95% confidence interval 0·49 to 0·78), moderate intensity (0·69, 0·60 to 0·79), and light intensity (0·56, 0·47 to 0·68). Interpretations: Physical activity should be recommended for older adults to reduce the risk of dementia. Funding Statement: This study used data from the Japan Gerontological Evaluation Study (JAGES), which was supported by JSPS(Japan Society for the Promotion of Science) KAKENHI Grant Number (JP15H01972), Health Labour Sciences Research Grant (H28-Choju-Ippan-002), Japan Agency for Medical Research and Development (AMED) (JP17dk0110017, JP18dk0110027, JP18ls0110002, JP18le0110009), the Research Funding for Longevity Sciences from National Center for Geriatrics and Gerontology (29-42). Declaration of Interests: The authors state there are no conflicts of interest to declare. Ethics Approval Statement: This study was reviewed and approved by ethics committees at the University of Tokyo, Nihon Fukushi University, National Center for Geriatrics and Gerontology, and Chiba University.