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

睡眠在阿尔茨海默病中起什么作用？

• 批准号: 9448108
• 负责人: Rebecca M C Spencer
• 金额: $ 55.86万
• 依托单位: UNIVERSITY OF MASSACHUSETTS AMHERST
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-07-15 至 2023-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9448108
• 关键词: Accounting; Age-associated memory impairment; Aging; Alzheimer disease prevention; Alzheimer' s Disease; Animal Model; Area; Behavioral; Brain; Cognitive; Cognitive aging; Corpus striatum structure; Dementia; Development; Disease; Elderly; Functional Magnetic Resonance Imaging; Goals; Health; Hippocampus (Brain); Impaired cognition; Impairment; Individual; Individual Differences; Intervention; Knowledge; Learning; Measures; Memory; Mission; Modeling; Motor; Onset of illness; Outcome; Performance; Physiological; Physiology; Polysomnography; Population; Prevention; Prevention strategy; Process; Public Health; Reporting; Research; Role; Sleep; Sleep Stages; Symptoms; Techniques; Testing; Training; United States National Institutes of Health; Visuospatial; Work; age related; aging brain; base; cognitive ability; cognitive function; cognitive process; density; healthy aging; improved; innovation; insight; memory consolidation; memory encoding; memory process; motor learning; neuroimaging; normal aging; novel; parent grant; procedural memory; relating to nervous system; resilience; spatiotemporal; treatment strategy; white matter; young adult

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.

项目概要 了解健康衰老过程中睡眠和记忆的变化对于预防和治疗老年痴呆症至关重要 衰老疾病，包括阿尔茨海默病。阿尔茨海默病早期就观察到睡眠不足 甚至可能早于阿尔茨海默病的发作。认知能力下降和睡眠同步下降 即使在健康老龄化过程中，也可以观察到数量和质量。鉴于对健康年轻人的大量研究 和动物模型说明睡眠对记忆和其他认知过程的好处， 该提案的目的是了解睡眠的变化是否会导致认知能力的变化 在健康老龄化中。该应用程序的具体目标是了解保存和保存的潜在因素 老年人睡眠依赖性记忆巩固不足。具体来说，研究将检验年龄是否 睡眠依赖性记忆处理的相关变化反映了睡眠生理、记忆的变化 编码，或两者兼而有之。睡眠在陈述性学习和程序性学习中的功能是独特的，并且各自相关 具有不同的睡眠阶段和生理标记。因此，陈述式学习和程序式学习将 分别探查。具体目标 1 将检查记忆编码中与年龄相关的变化是否有助于 依赖睡眠的陈述性记忆巩固。记忆的行为和神经测量 将检查编码。据推测，海马参与度和编码深度减少 与年轻人相比，老年人睡眠依赖性记忆处理减少但保留 成年人。第二个目的是检查与年龄相关的记忆变化相关的睡眠微观结构 合并。具体目标 2 将检查记忆编码中与年龄相关的变化是否有助于 减少依赖睡眠的程序性记忆巩固。据推测，老年人无法参与 海马体负责编码此类任务，这是睡眠依赖性记忆巩固的必要状态 发生。然而，额外的训练被认为可以对老年人产生依赖于睡眠的表现益处。 成年人。所提出的研究具有创新性，因为它将新颖的概念应用于认知衰老领域，完善了 研究睡眠依赖性记忆巩固（考虑编码能力）的方法，利用 该领域的新技术（高密度多导睡眠图，功能磁共振成像），并寻求改变治疗和 阿尔茨海默病的预防策略和睡眠目标衰老。此外，拟议的工作是 意义重大，因为它将为阿尔茨海默病的预防和治疗方法提供信息：如果个人 记忆编码或睡眠微观结构的差异减少了睡眠依赖性记忆处理，这些 可能是延缓阿尔茨海默病症状和其他形式的认知能力下降的目标。