Physical activity and risk of Alzheimer’s disease: a two-sample Mendelian randomization study

Baumeister, Sebastian E; Karch, André; Bahls, Martin; Teumer, Alexander; Leitzmann, Michael F; Baurecht, Hansjörg

Introduction Evidence from observational studies for the effect of physical activity on the risk of Alzheimer’s disease (AD) is inconclusive. We performed Mendelian randomization analysis to examine whether physical activity is a protective factor for AD. Methods Summary data of genome-wide association studies on physical activity and AD were identified using PubMed and the GWAS catalog. The study population included 21,982 AD cases and 41,944 cognitively normal controls. Eight single nucleotide polymorphisms (SNP) known at P < 5×10−8 to be associated with accelerometer-assessed physical activity served as instrumental variables. Results Genetically predicted accelerometer-assessed physical activity had no effect on the risk of AD (inverse variance weighted odds ratio [OR] per standard deviation (SD) increment: 1.03, 95% confidence interval: 0.97-1.10, P=0.332). Discussion The present study does not support a relationship between physical activity and risk of AD, and suggests that previous observational studies might have been biased.