Association between alcohol consumption and Alzheimer’s disease: A Mendelian Randomization Study

Abstract

INTRODUCTIONObservational studies have suggested that light-moderate alcohol consumptions decreases the risk of Alzheimers disease, but it is unclear if this association is causal.\n\nMETHODSTwo-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 Alzheimers disease (LOAD) or Alzheimers disease age of onset survival (AAOS). Additionally, {gamma}-glutamyltransferase levels were included as a positive control.\n\nRESULTSThere 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 {gamma}-glutamyltransferase blood concentrations. Alcohol dependence was associated with a delayed AAOS.\n\nDISCUSSIONMR 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.\n\nResearch in ContextO_ST_ABSSystematic ReviewC_ST_ABSThe authors reviewed the literature using online databases (e.g. PubMed). Previous research links light-moderate alcohol consumption to a decreased risk of Alzheimers disease (AD), however, prior studies based on observational study designs may be biased due to unmeasured confounders influencing both alcohol consumption and AD risk.\n\nInterpretationWe used a two-sample Mendelian randomization (MR) approach to evaluated the causal relationship between alcohol intake and AD. MR uses genetic variants as proxies for environmental exposures to provide an estimate of the causal association between an intermediate exposure and a disease outcome. MR found evidence of a causal association between alcohol consumption and an earlier AD age of onset, suggesting that light-moderate alcohol consumption does not reduce risk of Alzheimers disease.\n\nFuture DirectionsFuture studies should use alterative study designs and account for additional confounders when evaluating the causal relationship between alcohol consumption and AD.\n\nHighlightsO_LIWe evaluated causal relationships between alcohol intake and Alzheimers disease\nC_LIO_LIAlcohol consumption is causally associated with an earlier Alzheimers age of onset\nC_LIO_LINo evidence of causal assocations between alcohol intake and Alzheimers risk\nC_LI