The Link Between Physical Function, β-Amyloid, and Cognitive Aging in Women

This study aimed to examine associations between functional capacity (FC), brain β-amyloid (Aβ) burden, and longitudinal cognitive performance. Data from 89 cognitively normal women (70.0 ± 2.7 years) in the Women’s Healthy Ageing Project cohort were analyzed. FC was assessed using the timed up and go (TUG) test and the Aβ burden was quantified via a F-18 Florbetaben PET scan with Standardized Uptake Value Ratio (SUVR). Cognition was evaluated longitudinally using the Preclinical Alzheimer Cognitive Composite (PACC) over 3.9 ± 2.6 years. Multiple linear regression, mediation analysis, and linear mixed-effects models were applied. Baseline Aβ burden and years of education were associated with cognitive performance two to six years later, while the TUG performance was associated with cognitive outcomes at two years. Aβ burden was found to mediate the relationship between FC and cognition over time. A significant three-way interaction (TUG × SUVR × time) was observed, indicating that declines in the TUG performance over time were exclusively associated with steeper cognitive decline among women with elevated Aβ burden (SUVR ≥ 1.42). These findings suggest that maintaining functional mobility may be particularly relevant for women with increased Aβ burden and support future research targeting early motor-cognitive markers.