Objectives: To investigate whether moderate alcohol consumption has a favourable or adverse association or no association with brain structure and function.

Design: Observational cohort study with weekly alcohol intake and cognitive performance measured repeatedly over 30 years (1985-2015). Multimodal magnetic resonance imaging (MRI) was performed at study endpoint (2012-15).
Setting: Community dwelling adults enrolled in the Whitehall II cohort based in the UK (the Whitehall II imaging substudy).

Participants: 550 men and women with mean age 43.0 (SD 5.4) at study baseline, none were "alcohol dependent" according to the CAGE screening questionnaire, and all safe to undergo MRI of the brain at follow-up. Twenty three were excluded because of incomplete or poor quality imaging data or gross structural abnormality (such as a brain cyst) or incomplete alcohol use, sociodemographic, health, or cognitive data.

Main outcome measures: Structural brain measures included hippocampal atrophy, grey matter density, and white matter microstructure. Functional measures included cognitive decline over the study and cross sectional cognitive performance at the time of scanning.

Results: Higher alcohol consumption over the 30 year follow-up was associated with increased odds of hippocampal atrophy in a dose dependent fashion. While those consuming over 30 units a week were at the highest risk compared with abstainers (odds ratio 5.8, 95% confidence interval 1.8 to 18.6; P≤0.001), even those drinking moderately (14-21 units/week) had three times the odds of right sided hippocampal atrophy (3.4, 1.4 to 8.1; P=0.007). There was no protective effect of light drinking (1-<7 units/week) over abstinence. Higher alcohol use was also associated with differences in corpus callosum microstructure and faster decline in lexical fluency. No association was found with cross sectional cognitive performance or longitudinal changes in semantic fluency or word recall.

Conclusions: Alcohol consumption, even at moderate levels, is associated with adverse brain outcomes including hippocampal atrophy. These results support the recent reduction in alcohol guidance in the UK and question the current limits recommended in the US.