Combating Alzheimer's through sleep and exercise (CASE): A study protocol

Dementia affects over 55 million people worldwide, with Alzheimer's disease (AD) comprising most cases. Because curative therapies remain unavailable, there is an urgent need for prevention strategies that target modifiable risk factors. Behavioral interventions-particularly sleep improvement and physical activity-can independently benefit cognition, brain function, and cardiometabolic health, yet their combined (potentially synergistic) effects and scalable delivery models remain underexplored. This exploratory, hypothesis-generating, three-arm randomized controlled trial will evaluate: (1) whether improvements in sleep metrics are associated with improvements in cognitive performance and biomarker panels reflecting brain and cardiometabolic health; (2) the effects of structured, moderate-intensity aerobic and anaerobic exercise on cognitive performance and biomarker panels; (3) the combined effects of sleep and exercise interventions on cognitive performance and biomarker panels, including potential synergy; and (4) the role of light exposure as a modulator of sleep parameters. Over 8 weeks at a single site, 60 community-dwelling adults, aged 55-80 years, with and without mild cognitive impairment, will be randomized to exercise-only, sleep-only, or combined sleep-plus-exercise interventions. Programs will be delivered in-person and/or using Elemind Neuromodulation headbands, Fitbit trackers, and Lys light sensors. Cognitive function will be assessed with the Digital Neuro-Signature Platform, and plasma biomarkers will index cardiometabolic health and AD-related neuropathology. Findings will inform larger, multi-site trials targeting modifiable AD risk factors using scalable, digital, and decentralized intervention platforms. ClinicalTrials.gov NCT04855630; https://clinicaltrials.gov/study/NCT04855630 . Registration date 04/19/2021.