Sex differences in allostatic load profiles and incident dementia: The AGES-Reykjavik Study

Abstract

Background Allostatic load (AL), an umbrella term for the physiological response to chronic stress, is different in women and men. AL has also been associated with all-cause dementia. Objective The current study investigates if AL clusters differently in men and women, and if these sex-based clusters are associated with all-cause dementia. Methods The study included individuals without dementia (n = 5343, 58% women, age range: 66-98 years) at baseline from the AGES-Reykjavik Study, a population-based cohort study. AL markers of cardiovascular, lipid, neuroendocrine, and inflammatory components were assessed at baseline. Clustering of AL markers was done using latent profile analysis in men and women separately to create sex-specific AL risk groups. Sex-specific Cox regressions on the sex-specific AL risk groups, adjusted for age, education, and medical and lifestyle factors, were performed to assess if the relationship between AL and all-cause, Alzheimer's, and non-Alzheimer's dementia differed per sex. Results All-cause dementia was diagnosed in 1099 participants during follow-up (median: 10 years). Only cardiovascular and metabolic factors differed between AL groups in men. One of the groups in women, labeled 'Risk factors', was associated with a lower risk of AD dementia (HR 0.75; 95% CI 0.58; 0.98) compared to the 'Average' group. In men, a group labeled 'Multisystem dysregulation', consisting of mostly individuals with diabetes, was associated with an increased risk of all-cause dementia (HR 1.75; 95% CI 1.06; 2.90). Conclusions AL clustered differently in men and women. Metabolic dysregulation, specifically in men, was associated with all-cause dementia.