Sex differences in the association of alcohol with cognitive decline and brain pathology in a cohort of octogenarians

Rationale: The beneficial effects of moderate alcohol may differ in aging men versus women. Objectives: Cognitive and functional decline and neuropathology were investigated in a cohort of aging men and women with diverse alcohol histories. Methods: Non-demented (Clinical Dementia Rating (CDR) of ≤ 0.5 and a Mini-Mental State Examination (MMSE) score of > 24), autonomously living participants were tracked in longitudinal aging studies to examine self-report and objective tests of rates of decline in a cohort (n = 486) of octogenarians. Neurofibrillary tangles (NFTs; Braak stage) and neuritic plaques (NPs) were staged at autopsy in a subset of participants (n = 149) using current standard neuropathologic diagnostic criteria. Results: Moderate drinking men had an attenuated rate of decline compared to rare/never drinkers and women on the MMSE and CDR sum of boxes. In contrast, moderate drinking women had a reduced rate of decline only in the Logical Memory Delayed Recall Test (LMDR) compared to rare/never drinkers and men. Moderate alcohol consumption was associated with a reduction in the incidence of advanced (stages 5–6) Braak NFT stage in men (p < 0.05), with no effect in women. Conclusions: In this cohort, men experienced a broader range of beneficial effects associated with alcohol. Alcohol’s effects may differ in men and women in important ways that suggest a narrower beneficial window.