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

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... (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.