Slow-wave sleep enhancement in those at risk for Alzheimer's disease: Links with memory, excitotoxicity, and plasma A-beta

慢波睡眠可增强阿尔茨海默病风险人群：与记忆、兴奋性毒性和血浆 A-β 的联系

• 批准号: 10436846
• 负责人: Kristine Ann Wilckens
• 金额: $ 69.57万
• 依托单位: UNIVERSITY OF PITTSBURGH AT PITTSBURGH
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-07-01 至 2026-03-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10436846
• 关键词: Address; Adult; Affect; Age; Aging; Alzheimer' s Disease; Alzheimer' s disease pathology; Alzheimer' s disease risk; Amyloid beta-Protein; Apolipoprotein E; Beds; Behavior Therapy; Behavioral; Biological; Biological Assay; Cognition; Cognitive; Dementia; Disease; Education; Elderly; Exhibits; Functional Magnetic Resonance Imaging; Functional disorder; Glutamate Receptor; Gold; Health behavior; Hippocampus (Brain); Home; Impaired cognition; Intervention; Link; Mass Spectrum Analysis; Measures; Mediating; Memory; Nerve Degeneration; Neurons; Nonpharmacologic Therapy; Pathway interactions; Pharmacology; Pittsburgh Compound-B; Plasma; Play; Positron-Emission Tomography; Process; Proteins; Race; Research; Retirement; Role; Sleep; Sleep Apnea Syndromes; Sleeplessness; Slow-Wave Sleep; Synapses; Therapeutic Intervention; Time; abeta accumulation; abeta deposition; behavioral study; cognitive change; cognitive function; cognitive performance; cognitive testing; cost; excitotoxicity; executive function; human old age (65+); improved; indexing; intervention effect; memory retention; neuroimaging; neuroimaging marker; neurotoxic; non rapid eye movement; normal aging; pre-clinical; preservation; sex; sleep behavior; sleep difficulty; uptake

Dementia caused by Alzheimer’s disease affects approximately 5.6M adults over age 65, with costs expected to rise from $307B to $1.5T over the next 30 years. Behavioral interventions have shown promise for mitigating neurodegeneration and cognitive impairments. Sleep is a modifiable health behavior that is critical for cognition and deteriorates with advancing age and Alzheimer’s disease. Thus, it is a priority to examine whether improving sleep modifies Alzheimer’s disease pathophysiology and cognitive function. Our research suggests that deeper, more consolidated sleep is positively associated with memory and executive functions and networks that underlie these processes. Our preliminary studies confirm that time-in-bed restriction interventions increase sleep efficiency and non-rapid eye movement slow-wave activity (SWA) and suggest that increases in SWA are associated with improved cognitive function. SWA reflects synaptic downscaling predominantly among prefrontal connections. Downscaling of prefrontal connections with the hippocampus during sleep may help to preserve the long-range connections that support memory and cognitive function. In pre-clinical Alzheimer’s disease, hyperactivation of the hippocampus is thought to be excitotoxic and is shown to leave neurons vulnerable to further Aβ deposition. Synaptic downscaling through SWA may mitigate the progression of Alzheimer’s disease through these pathways. The proposed study will behaviorally increase sleep depth (SWA) through four weeks of time-in-bed restriction in older adults characterized on Aβ deposition and multiple factors associated with Alzheimer’s disease risk. We will examine whether behaviorally enhanced SWA reduces hippocampal hyperactivation, leading to improved task-related prefrontal-hippocampal connectivity, plasma Aβ levels, and cognitive function. This research addresses whether a simple, feasible, and scalable behavioral sleep intervention improves functional neuroimaging indices of excitotoxicity, Alzheimer’s pathophysiology, and cognitive performance.

由阿尔茨海默病引起的痴呆症影响了大约560万65岁以上的成年人，其成本预计会很高