Neurobiological mechanisms of sleep and exercise effects on memory in older adults at risk for Alzheimer's disease

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PROJECT SUMMARY Alzheimer’s disease is a progressive form of dementia with no effective treatments. Episodic memory deficits are a defining cognitive symptom of Alzheimer’s disease, which may be related to changes in the medial temporal lobes (MTL). The MTL facilitates episodic memory function and is particularly vulnerable to Alzheimer’s disease pathology. Both sleep and exercise are linked to episodic memory function, including pattern separation operations reliant on the MTL. Evidence in young adults suggests that sleep and exercise are each independently linked to mnemonic discrimination (behavioral correlate of pattern separation), but it is unclear whether they interact to do so, and through what mechanisms. Whether these relationships are altered in older adults at-risk for Alzheimer’s disease is also unknown. To fill this knowledge gap, the proposed study will record high-density electroencephalography (hdEEG) during overnight sleep to measure the topographically specific (i.e., local) expression of non-rapid eye movement sleep slow-wave activity (SWA) and fast sleep spindle activity, administer a memory task assessing mnemonic discrimination prior to and following sleep to measure sleep-dependent memory consolidation, and collect questionnaire data assessing exercise frequency and duration from 56 older adults with heightened Alzheimer’s disease risk. High-resolution resting-state functional magnetic resonance imaging (hr-rsfMRI) data previously collected from this same participant cohort will be analyzed to measure resting-state network modularity. The project will address three specific aims: (1) determine whether local expression of SWA and fast spindle activity are associated with sleep-dependent memory consolidation in older adults, (2) determine whether network modularity is associated with sleep-dependent memory consolidation and local sleep expression in older adults, and (3) determine whether exercise is associated with local expression of SWA and fast spindle activity and network modularity. This project will provide the applicant with comprehensive training in memory theory, advanced statistical modelling, and cutting-edge analytical methods for hr-rsfMRI and hdEEG data. This research and training plan will prepare the applicant for an independent academic research career and will provide novel insights into the neurobiological mechanisms supporting the relationships among sleep, exercise, and memory consolidation in older adults at-risk for Alzheimer’s disease. Findings from this project could guide prospective exercise and sleep-based interventional studies to improve memory function and inform public health recommendations to reduce Alzheimer’s disease risk by underscoring the importance of sleep.