What is sleep's role in Alzheimer's disease? Insight from healthy aging

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PROJECT SUMMARY Understanding changes in sleep and memory in healthy aging is critical to prevention and treatment of diseases of aging including Alzheimer’s disease. Deficits in sleep are observed early in Alzheimer’s disease and may even precede Alzheimer’s disease onset. Decreased cognitive abilities and a parallel decline in sleep quantity and quality are observed even in healthy aging. Given a wealth of research in healthy young adults and animal models illustrating a benefit of sleep on memory and other cognitive processes, the overarching objective of this proposal is to understand whether changes in sleep account for changes in cognitive abilities in healthy aging. The specific objective of this application is to understand factors underlying preserved and deficient sleep-dependent memory consolidation in older adults. Specifically, studies will examine whether age- related changes in sleep-dependent memory processing reflect changes in sleep physiology, memory encoding, or both. Sleep’s function on declarative and procedural learning is unique, each being associated with distinct sleep stages and physiological markers. Therefore, declarative and procedural learning will be probed seperately. Specific Aim 1 will examine whether age-related changes in memory encoding contribute to sleep-dependent declarative memory consolidation. Both behavioral and neural measures of memory encoding will be examined. It is hypothesized that reduced hippocampal engagement and depth of encoding compared to young adults underlies reduced but preserved sleep-dependent memory processing in older adults. The secondary aim is to examine sleep microstructure associated with age-related changes in memory consolidation. Specific Aim 2 will examine whether age-related changes in memory encoding contribute to reduced sleep-dependent procedural memory consolidation. It is hypothesized that older adults fail to engage the hippocampus at encoding of such tasks, a necessary state for sleep-dependent memory consolidation to occur. However, additional training is hypothesized to yield sleep-dependent performance benefits in older adults. The proposed research is innovative as it applies a novel concept to the field of cognitive aging, refines the approach to studies of sleep-dependent memory consolidation (accounting for encoding capacity), utilizes novel techniques for this field (high-depensity polysomnography, fMRI), and seeks to shift the treatment and preventive strategies for Alzheimer’s disease and aging to sleep targets. Moreover, the proposed work is significant as it will inform approaches to Alzheimer’s disease prevention and treatment: if individual differences in memory encoding or sleep microstructure reduce sleep-dependent memory processing, these may be targets for delaying onset of Alzheimer’s disease symptoms and other forms of cognitive decline.