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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.
Glossary
- AD=
- Alzheimer disease;
- CI=
- confidence interval;
- DSM-IV=
- Diagnostic and Statistical Manual of Mental Disorders, 4th edition;
- GWAS=
- genome-wide association studies;
- IVW=
- inverse-variance weighted;
- MET=
- metabolic equivalent task;
- MR-Egger=
- mendelian randomization–Egger;
- MR-PRESSO=
- mendelian randomization–Pleiotropy Residual Sum and Outlier;
- OR=
- odds ratio;
- SNP=
- single nucleotide polymorphism
Footnotes
Go to Neurology.org/N for full disclosures. Funding information and disclosures deemed relevant by the authors, if any, are provided at the end of the article.
↵* These authors contributed equally to this work.
This Null Hypothesis article is published as part of a collaborative effort between Neurology® and CBMRT.
- Received November 21, 2019.
- Accepted in final form April 10, 2020.
- © 2020 American Academy of Neurology
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