Whitsel N, Reynolds CA, Buchholz EJ, et al. - Findings from this prospective cohort observational study suggest advanced brain aging by age 56 in men who displayed heavier smoking and alcohol consumption by age 40.

• Participants were male twins of predominantly European ancestry who served in the United States military and began undergoing structural magnetic resonance imaging (MRI) at an average age 56.

• Structural equation modelling indicated predictive value of age 40 pack years for more advanced age 56 predicted brain age difference scores (PBAD).

• More advanced PBAD scores at age 56 were predicted by age 40 alcohol consumption; additional influences of age 40 alcohol consumption were evident at age 62.

• Some genetic mechanisms appeared to be partially underlying effects of alcohol, but not smoking, on PBAD.