Association between alcohol consumption and Alzheimer's disease: A Mendelian randomization study

INTRODUCTION: Observational studies have suggested that light-to-moderate alcohol consumption decreases the risk of Alzheimer's disease, but it is unclear if this association is causal. METHODS: Two-sample Mendelian randomization (MR) analysis was used to examine whether alcohol consumption, alcohol dependence, or Alcohol Use Disorder Identification Test (AUDIT) scores were causally associated with the risk of Late-Onset Alzheimer's disease (LOAD) or Alzheimer's disease age of onset survival (AAOS). Additionally, γ-glutamyltransferase levels were included as a positive control. RESULTS: There was no evidence of a causal association between alcohol consumption, alcohol dependence, or AUDIT, and LOAD. Alcohol consumption was associated with an earlier AAOS and increased γ-glutamyltransferase blood concentrations. Alcohol dependence was associated with a delayed AAOS. DISCUSSION: MR found robust evidence of a causal association between alcohol consumption and an earlier AAOS, but not alcohol intake and LOAD risk. The protective effect of alcohol dependence is potentially due to survivor bias.