Aging, sleep, and beta-amyloid pathology and their impact on memory

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DESCRIPTION (provided by applicant): Older adults experience disrupted sleep, with reductions in non-rapid eye movement (NREM) slow-wave sleep (SWS) being most prominent. In parallel with alterations of sleep is the cognitive hallmark of aging; a progressive impairment in the ability to form and retain new episodic memories. Within the last ten years, an established literature now suggests that sleep, particularly SWS, is critical for supporting the learning and retention of new episodic memories. Nevertheless, the relationship between age-related alterations of sleep and cognitive memory decline in later life remains poorly understand. The accumulation of central 2- amyloid in later life represents a potential link between these two factors of sleep and memory. Specifically, cortical build-up of 2-amyloid predicts episodic memory decline in healthy aging and Alzheimer's disease. Further, cortical regions associated with the greatest accumulation of 2-amyloid overlap with the cortical regions known to generate SWS. Moreover, it has been demonstrated that brain concentrations of 2- amyloid are tightly coupled to the sleep-wake cycle, and that sleep loss results in an increased presence of 2-amyloid plaques. If correct, this relationship between SWS and 2-amyloid would represent an important, but as yet uncharacterized, feature of cognitive aging, representing a novel treatment target using already existing methods known to enhance SWS. Combining in vivo brain imaging of 2-amyloid (PIB-PET) with high-density EEG measures of sleep and next day brain imaging (fMRI) of episodic learning, this proposal aims to characterize the relationship between 2-amyloid and sleep, and will examine their combined effects on brain function and episodic learning ability. PUBLIC HEALTH RELEVANCE: Combining in vivo brain imaging of 2-amyloid (PIB-PET) with high-density EEG measures of sleep and next day brain imaging (fMRI) of episodic learning, this proposal aims to characterize the relationship between altered sleep, impaired memory, and 2-amyloid brain pathology in later life. These studies examine a novel pathway by which healthy aging may be promoted, affording substantive clinical, societal and public health advantages for older adult populations.