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: 9884697
• 负责人: Rebecca M C Spencer
• 金额: $ 54.56万
• 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/9884697
• 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; Polysomnography; Population; Prevention; Prevention strategy; Process; Public Health; Reporting; Research; Role; Sleep; Sleep Deprivation; Sleep Stages; Sleep disturbances; 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; improvement on sleep; innovation; insight; memory consolidation; memory encoding; memory process; motor learning; neuroimaging; normal aging; novel; parent grant; preservation; procedural memory; relating to nervous system; resilience; sleep physiology; sleep quality; sleep quantity; sleep spindle; 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.

项目总结 了解健康衰老过程中睡眠和记忆的变化对预防和治疗老年痴呆症至关重要 老年性疾病，包括阿尔茨海默病。睡眠不足在阿尔茨海默病的早期被观察到 甚至可能早于阿尔茨海默病的发病。认知能力下降和睡眠同时下降 即使在健康的衰老过程中，也能观察到数量和质量。鉴于对健康年轻人的大量研究 动物模型说明了睡眠对记忆和其他认知过程的好处，最重要的是 这项建议的目的是了解睡眠的变化是否会导致认知能力的变化 在健康的衰老中。此应用程序的特定目标是了解保存和保存 老年人睡眠依赖记忆巩固不足。具体地说，研究将检查年龄是否- 睡眠依赖记忆处理的相关变化反映了睡眠生理、记忆 编码或两者兼而有之。睡眠对陈述性学习和程序性学习的作用是独一无二的，每种功能都是相互关联的 有不同的睡眠阶段和生理标志。因此，陈述性和程序性学习将是 分开探查。具体目标1将检查记忆编码中与年龄相关的变化是否起作用 涉及睡眠依赖的陈述性记忆巩固。记忆的行为和神经测量 我们将研究编码。据推测，减少了海马区的参与和编码深度 与年轻人相比，老年人睡眠依赖记忆处理能力减弱但仍能保持 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结构 整合。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 减少了依赖睡眠的程序性记忆巩固。假设老年人不能参与 海马体在编码这样的任务时，是睡眠依赖记忆巩固的必要状态，以 发生。然而，额外的训练被假设为在老年人中产生睡眠依赖的表现好处 成年人。这项拟议的研究具有创新性，因为它将一个新的概念应用到认知衰老领域，精炼道 研究睡眠依赖记忆巩固(考虑编码能力)的方法，利用 该领域的新技术(高依赖性多导睡眠图，fMRI)，并寻求将治疗和 阿尔茨海默病的预防策略和睡眠目标的老化。此外，拟议的工作是 意义重大，因为它将为阿尔茨海默病预防和治疗方法提供信息：如果个人 记忆编码或睡眠微结构的差异减少了睡眠相关的记忆处理，这些 可能是延缓阿尔茨海默病症状和其他形式认知衰退的目标。