Allostatic load (AL), an index of cumulative physiological dysregulation from chronic stress, may contribute to Alzheimer's disease (AD) pathophysiology by accelerating brain aging. Higher AL has been Show more
Allostatic load (AL), an index of cumulative physiological dysregulation from chronic stress, may contribute to Alzheimer's disease (AD) pathophysiology by accelerating brain aging. Higher AL has been associated with AD-related biomarkers, suggesting a mechanistic connection. Lifestyle factors influence both AL and AD vulnerability, but their moderating role in AL-AD biomarker associations remains unclear. We included 111 cognitively unimpaired older adults from the baseline visit of the Age-Well trial. AL was computed as a composite score of 18 biomarkers spanning neuroendocrine, immune, metabolic, cardiovascular-respiratory, and anthropometric systems. Plasma biomarkers included amyloid beta (Aβ)42, Aβ40, phosphorylated-tau (p-tau231), glial fibrillary acidic protein (GFAP), and neurofilament light chain (NfL). Physical activity, Mediterranean diet adherence, and cognitive activity were assessed using validated questionnaires. Multiple linear regressions tested associations between AL and (1) AD-related biomarkers and (2) lifestyle factors, as well as their interactions, controlling for age, sex, education, apolipoprotein E ε4 (APOE ε4) status, and glomerular filtration rate (GFR). Higher AL was associated with higher Aβ42/Aβ40 ratio ( Regular physical activity was associated with a weaker relationship between AL and early AD-related biomarkers in this cross-sectional sample. Longitudinal studies should confirm whether maintaining physical activity attenuates stress-related physiological dysregulation and reduces AD vulnerability. Show less