Physical activity and risk of Alzheimer disease: A 2-sample mendelian randomization study

Neurology. 2020 Sep 29;95(13):e1897-e1905. doi: 10.1212/WNL.0000000000010013. Epub 2020 Jul 17.

Abstract

Objective: Evidence from observational studies for the effect of physical activity on the risk of Alzheimer disease (AD) is inconclusive. We performed a 2-sample mendelian randomization analysis to examine whether physical activity is protective for AD.

Methods: Summary data of genome-wide association studies on physical activity and AD were used. The primary study population included 21,982 patients with AD and 41,944 cognitively normal controls. Eight single nucleotide polymorphisms (SNPs) known at p < 5 × 10-8 to be associated with average accelerations and 8 SNPs associated at p < 5 × 10-7 with vigorous physical activity (fraction of accelerations >425 milligravities) served as instrumental variables.

Results: There was no association between genetically predicted average accelerations with the risk of AD (inverse variance weighted odds ratio [OR] per SD increment: 1.03, 95% confidence interval 0.97-1.10, p = 0.332). Genetic liability for fraction of accelerations >425 milligravities was unrelated to AD risk.

Conclusion: The present study does not support a causal association between physical activity and risk of AD.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Aged, 80 and over
  • Alzheimer Disease / genetics*
  • Biological Specimen Banks
  • Case-Control Studies
  • Exercise*
  • Female
  • Genetic Predisposition to Disease / genetics*
  • Genome-Wide Association Study / statistics & numerical data
  • Humans
  • Male
  • Mendelian Randomization Analysis*
  • Middle Aged
  • Polymorphism, Single Nucleotide
  • Risk Factors