UC Irvine

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 physical activity 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, a series of studies were conducted. In Chapter 2, self-report measurements of sleep, physical activity, and cognitive function were used to statistically model the mediating effect of sleep in the physical activity-cognition relationship. In Chapters 3 and 4, high-density electroencephalography was recorded during overnight sleep to measure the expression and coupling of non-rapid eye movement (NREM) sleep oscillations, a memory task assessing mnemonic discrimination was administered prior to and following sleep to measure sleep-dependent memory consolidation, and questionnaire data assessing physical activity frequency and duration was collected from 36 older adults. High-resolution resting-state functional magnetic resonance imaging data previously collected from this same participant cohort was analyzed to derive measures of resting-state network modularity and MTL centrality. Chapters 3 and 4 addressed three specific aims: (1) whether local expression and coupling of NREM sleep oscillations are associated with sleep-dependent memory consolidation (Chapter 3), (2) whether network modularity and measures of MTL centrality are associated with sleep-dependent memory consolidation (Chapter 3), and (3) whether physical activity is associated with these same mechanisms (Chapter 4). This research provides novel insights into the neurobiological mechanisms supporting the relationships among sleep, physical activity, and memory consolidation in older adults. Findings from this dissertation could guide prospective physical activity 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.