Longitudinal effects of physical activity on sleep in association with hippocampal-amygdala subfield structure and functional connectivity in Alzheimer's disease.

INTRODUCTION: Sleep is a modifiable risk factor in Alzheimer's disease (AD), but its relationship to medial temporal lobe (MTL) subfields and responsiveness to lifestyle interventions remain unclear. METHODS: In the Dementia-Multi-Objective Validation of Exercise (MOVE) study, 46 individuals on the AD continuum were randomized to 6 months of multimodal exercise (n = 25) or psychoeducation (n = 21) and followed for 18 months (T1-T4). Clinical and cognitive testing, sleep/activity measures (PSQI, diaries, wearables), high-resolution T1, and resting-state functional magnetic resonance imaging scans were acquired. Hippocampal and amygdala subfield volumes and hippocampus-amygdala connectivity were analyzed longitudinally. RESULTS: After the 6-month intervention, the intervention group showed increased hippocampus-amygdala connectivity and attenuated subfield atrophy. One year later, both groups progressed in cognitive decline and hippocampal atrophy. Hippocampal and amygdalar volumes and connectivity were associated with sleep parameters as well as activity and cognitive parameters. DISCUSSION: Exercise was associated with short-term MTL preservation and network reorganization linked to sleep and activity, supporting continuous physical activity for lasting benefits.