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The aim was to examine cross-sectional association between moderate alcohol consumption and total brain volume in a cohort of participants in early middle-age, unconfounded by age-related neuronal change. 353 participants aged 39 to 45 years reported on their alcohol consumption using the AUDIT-C measure. Participants with alcohol abuse were excluded. Brain MRI was analyzed using a fully automated method. Brain volumes were adjusted by intracranial volume expressed as adjusted total brain volume (aTBV). AUDIT-C mean of 3.92 ( SD  2.04) indicated moderate consumption. In a linear regression model, alcohol consumption was associated with smaller aTBV ( B  = − 0.258,  p  < .001). When sex and current smoking status were added to the model, the association remained significant. Stratified by sex, the association was seen in both males ( B  = − 0.258,  p  = 0.003) and females ( B  = − 0.214,  p  = 0.011). Adjusted for current smoking, the association remained in males ( B  = − 0.268,  p  = 0.003), but not in females. When alcohol consumption increased, total brain volume decreased by 0.2% per one AUDIT-C unit already at 39–45 years of age. Moderate alcohol use is associated with neuronal changes in both males and females suggesting health risks that should not be overlooked.

Moderate alcohol use is associated with decreased brain volume in early middle age in both sexes