• Setor K Kunutsor, Jari A Laukkanen, Jussi Kauhanen, and Peter Willeit.
• National Institute for Health Research Bristol Biomedical Research Centre, University Hospitals Bristol and Weston NHS Foundation Trust and the University of Bristol, Bristol, UK.
• Eur. J. Clin. Invest. 2021 Mar 1; 51 (3): e13415.

BackgroundWhile it is well established that physical activity is associated with reduced risk of vascular and nonvascular outcomes as well as mortality, evidence on the association between physical activity and dementia is inconsistent. We aimed to assess the associations of physical activity with the risk of dementia and Alzheimer's disease (AD).Material And MethodsWe analysed data on 2394 apparently healthy men with good baseline cognitive function from the prospective population-based Kuopio Ischaemic Heart Disease study. We assessed habits of physical activity at baseline using a 12-month leisure time physical activity (LTPA) questionnaire. Using Cox regression, we calculated hazard ratios adjusted for body mass index, systolic blood pressure, smoking status, history of type-2 diabetes, total cholesterol, high-density lipoprotein cholesterol, alcohol consumption, history of coronary heart disease and high-sensitivity C-reactive protein.ResultsDuring a median follow-up of 24.9 years (interquartile range: 18.3-26.9), 208 men developed dementia and 128 developed AD. Multivariable adjusted hazard ratios for dementia comparing top vs bottom tertiles of physical activity were 0.97 (95% confidence intervals: 0.69-1.38) for total physical activity volume, 0.96 (0.69-1.34) for conditioning LTPA volume and 1.13 (0.80-1.61) for total LTPA volume. Corresponding hazard ratios for AD were 1.19 (0.76-1.85), 0.98 (0.64-1.49) and 1.22 (0.77-1.93). Associations were consistent in analyses restricted to participants with ≥10 years of follow-up.ConclusionsIn middle-aged Caucasian men, various physical activity exposures were not associated with all-cause dementia or AD. Future studies should address biases due to reverse causation and regression dilution and should involve objective measures of physical activity.© 2020 The Authors. European Journal of Clinical Investigation published by John Wiley & Sons Ltd on behalf of Stichting European Society for Clinical Investigation Journal Foundation.

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