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

Abstract

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.

Keywords: Alcohol; Alzheimer’s disease; Cognitive aging; Dementia; Neuropathology; Sex differences.

Figure 1

Study Participants Flow diagram depicting inclusion and exclusion of participants in the study. OBAS: Oregon Brain Aging Study; ISAAC: Intelligent Systems for Assessing Aging Changes, EtOH: alcohol.

Figure 2

Neuropsychological Measures Moderate drinking groups exhibit reduced rates of decline and differ in men and women. Annual rates of decline on the (A) Logical Memory Delayed task (LMDR), (B) Mini-Mental State Examination (MMSE) and (C) Clinical Dementia Rating (CDR) sum of boxes over time for individual subjects. Annualized rates of change are taken from the mixed-effects models with subject-specific random effects included and fixed-effects rates indicated for each group. Individuals in the moderate alcohol drinking groups exhibited reduced decline in both women and men, but on different tasks. Rates of decline were reduced in the group of moderate drinking women on the LMDR and in the moderate drinking group of men slowed on the MMSE and CDR sum of boxes. ** p < 0.01, *** p < 0.001 comparing same-sex rare/never drinkers to moderate drinkers. # p < 0.05, ## p < 0.01 comparing the effect of moderate drinking between men and women.