Abstract
Relationship between alcohol drinking and incident dementia remained uncertain. This study used UK Biobank cohort data to investigate the association between alcohol drinking and dementia risk, and potential effect modifications by cardiovascular disease (CVD) risk, APOE4 gene, and sex. We excluded infrequent drinkers and participants with baseline dementia or dementia within two years of follow-up. Drinking status was defined as non-drinking, low-moderate and heavy drinking (by weekly alcohol units). Drinking behaviors included drinking with meals and drinking type. Primary outcome was all-cause dementia. Hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated by multivariable Cox regression models. Subgroup analyses stratified by CVD risk, APOE4 gene, and sex were conducted. Among 296,715 participants (mean age 56.54 years), 4,242 developed dementia over a median follow-up of 13.7 years. Compared to non-drinking, low-moderate drinking reduced dementia risk (HR, 0.65; 95% CI, 0.59-0.73), while heavy drinking showed no significant association (HR, 0.88; 95% CI, 0.75-1.02). All drinking behaviors lowered dementia risk. Low-moderate drinking reduced dementia risk across subgroups: high/low CVD risk (HR 0.66, 95% CI 0.59-0.74/0.43, 0.30-0.61), APOE4 carriers/non-carriers (HR 0.71, 0.61-0.83/0.61, 0.52-0.71), females/males (HR 0.67, 0.58-0.77/0.63, 0.53-0.76). Compared with non-drinking, low-moderate drinking is associated with lower incident dementia risk, regardless of CVD risk, APOE4 gene, and sex. The protective effect of alcohol drinking was consistent among various drinking behaviors. Thus, this study confirmed the protective effect of low-moderate drinking in population, and provided insights for improving alcohol-related public health guidelines for dementia prevention.