Microstructural Brain Reserve Moderates the Associations Between 24-h Movement Behaviors and Cognition in Older...

This study examined the associations between 24-h movement behaviors and cognitive function in cognitively unimpaired older adults, and whether Alzheimer's disease brain signatures, including gray matter mean diffusivity (GMMD) and thickness/volume signatures, moderated these associations. A total of 91 participants were enrolled in the AGUEDA trial (NCT05186090), with 89 included in this cross-sectional analysis (mean age = 71.61 ± 3.85 years; 56.2% females). Moderate-to-vigorous physical activity (MVPA), light physical activity (LPA), sedentary behavior (SB), and sleep were objectively assessed using 9-day wrist-worn accelerometry. Cognitive function was assessed across attention/inhibitory control, episodic memory, processing speed, visuospatial processing, and working memory. Thickness/volume and GMMD signatures were derived from cortical and hippocampal regions. Compositional linear regression models (CoDA) examined associations, adjusting for age, sex, and education, and tested interactions between movement behaviors and Alzheimer's disease brain signatures. No direct associations were observed between 24-h movement behaviors and cognitive domains (all p > 0.05). However, GMMD signature, but not thickness/volume signature, moderated several movement behavior-cognition associations. Moderation was most evident for episodic memory, with significant interactions for MVPA, LPA, and sleep, while LPA exhibited the broadest pattern of moderation across cognitive domains, interacting with attention/inhibitory control, episodic memory, processing speed, and working memory (all p for interaction ≤ 0.04). In conclusion, the associations between 24-h movement behaviors and cognitive function may depend on microstructural brain integrity (i.e., GMMD). These findings highlight the importance of considering Alzheimer's disease-related brain signatures when investigating lifestyle-cognition associations and support a more personalized approach to promoting cognitive health in older adults. Future prospective longitudinal studies and CoDA interventional trials are needed to establish temporal precedence and evaluate whether targeted time reallocations can actively attenuate cognitive trajectories across distinct microstructural vulnerability profiles. Trial Registration: NCT05186090.