Sex‐specific biomarkers in Alzheimer's disease progression: Framingham Heart Study

BACKGROUND: Sex differences in Alzheimer's disease (AD) are not well understood. METHODS: We performed sex‐specific analyses of AD and annualized cognitive decline with clinical and blood biomarker data in participants 60+ years old in the community‐based longitudinal Framingham Heart Study Offspring Cohort (n = 1398, mean age 68 years, 55% women). RESULTS: During 11 years of follow‐up, women were 96% more likely than men to be diagnosed with clinical AD dementia after adjusting for age and education in the younger age group 60 to 70 years (n = 946; 95% confidence interval [CI], 1.08 to 3.56) although not in the older age group (70+) (n = 452; hazard ratio = 0.98; 95% CI, 0.68 to 1.53). Sex‐differences in incident AD rates decreased with increasing levels of education. The total contribution of the biomarkers to AD risk variance was 7.6% in women and 11.7% in men. One unit (pg/ml) lower plasma Aβ42 was associated with 0.0095 unit faster memory decline in women (p = 0.0002) but not in men (p = 0.55) after adjusting for age and education. DISCUSSION: Our study suggests that both early life and later‐life pathological factors may contribute to potential sex differences in incident AD.