Alzheimer’s disease (AD) begins silently in the brain, many years before memory problems appear. Research shows that disruptions in sleep and daily circadian (internal clock) rhythms are among the earliest signs in AD, detectable prior to memory symptoms. Additionally, poor sleep appears to actively contribute to the buildup of harmful brain proteins that cause AD, amyloid and tau. However, we still do not understand how specific sleep and circadian changes relate to different early stages of AD, and the biological mechanisms and directions of the links between sleep disruption and AD brain changes. This project aims to clarify how sleep disturbances, brain wave (EEG) signals during sleep, immune function, and metabolic health interact in the earliest, “preclinical” stages of AD, when intervention may be the most effective. By taking advantage of established research cohorts of older adults, this study will determine whether AD-related sleep-EEG patterns appear before, alongside, or after early AD stages of amyloid and tau buildup. Analyses of stored blood and spinal fluid samples will test if changes in metabolism and immune activity are linked to specific sleep-EEG disturbances at different disease stages. The results will help identify sleep-based and biological markers that signal preclinical AD and point to specific pathways that could be targeted with treatment.
This project will then test the accuracy of sleep-EEG markers from sleep studies at a clinical sleep center, potentially turning routine sleep testing into a tool for early AD detection. An exploratory pilot study will examine whether improving metabolic health can enhance sleep quality and favorably shift sleep-EEG and biofluid-based AD biomarkers. Altogether, this project will develop practical, biology-based strategies to noninvasively identify AD and target underlying metabolic and immune mechanisms, years before cognitive symptoms begin.
