Abstract: Background and aims: Consensus is lacking on whether light to moderate consumption of alcohol compared to abstinence is neuroprotective. In this study, we investigated the relationship between self-reported alcohol use and brain volume change over 2 years in middle-aged subjects. Methods: A sample of 162 subjects (aged 40–59 at baseline) from the PREVENT-Dementia programme underwent MRI scans on two separate occasions (mean interval 734 days; SD 42 days). We measured longitudinal rates of brain atrophy using the FSL Siena toolbox, and change in hippocampal volume from segmentation in SPM. Results: Controlling for age and sex, there were no significant associations of either total brain, ventricular, or hippocampal volume change with alcohol consumption. Adjusting for lifestyle, demographic and vascular risk factors did not alter this. Conclusions: We did not find any evidence of influence of alcohol consumption on changes in brain volume over a 2-year period in 40–60-year-olds.