Alcohol use and dementia in diverse populations (F96)
Topiwala A., Levey D., Zhou H., Deak J., Adhikari K., Ebmeier KP., Bell S., Burgess S., Nichols TE., Gaziano M., Stein M., Gelernter J.
Background: The impact of alcohol use on dementia risk remains contentious. Methodological limitations of previous studies have made distinguishing causation from con- founding difficult. Mendelian randomization is a quasi- experimental method that can estimate causal effects via genetics. Methods: We estimated dose-response relationships be- tween alcohol and dementia in observational and genetic analyses. First, we pooled and harmonized individual-level phenotype data from two prospective cohort studies: the US Million Veteran Program (MVP) and UK Biobank (UKB; mean follow-up 4 and 12 years respectively). Associations were examined using Cox regression analysis and results combined using random-effects meta-analysis. We compared these findings with genetic associations between alcohol use and dementia (calculated de novo) using data from 2.4 mil- lion participants using Mendelian randomization. Results: 559,559 participants (247,136 from MVP and 312,423 from UKB) aged 56-72 years old at baseline were included in observational analyses. 14,540 developed dementia and 48,034 died during follow-up. Observational as- sociations between alcohol and dementia were U-shaped, meaning that non-drinkers, heavy (> 40 drinks per week) drinkers (hazard ratio = 1.41 [1.15 to 1.74]) and dependent drinkers (1.51 [1.42-1.60]) were all at higher dementia risk compared with light drinkers. In contrast, genetic analyses revealed a monotonically increasing association between alcohol dose and dementia, with no evidence supporting a protective effect of any level of drinking. A two-fold in- crease in genetically-predicted alcohol use disorder prevalence was associated with a 16 % increase in dementia cases (IVW OR = 1.16 [1.03-1.30]), and a one standard deviation in- crease in log-transformed drinks per week was associated with a 15% increase (IVW OR = 1.15[1.03-1.27]). Discussion: Alcohol consumption has a causal role for dementia. Halving the population prevalence of alcohol use disorder would lead to a 16% reduction in dementia cases.