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.

项目摘要 了解健康衰老中睡眠和记忆的变化对于预防和治疗至关重要 包括阿尔茨海默氏病在内的衰老疾病。在阿尔茨海默氏病早期观察到睡眠不足 甚至可能先于阿尔茨海默氏病发作。认知能力降低和睡眠平行下降 即使在健康的衰老中也观察到数量和质量。在健康的年轻人中进行了大量研究 和动物模型说明睡眠对记忆和其他认知过程的好处， 该提议的目的是了解睡眠变化是否占认知能力的变化 在健康的衰老中。本应用的具体目的是了解保留的基本因素和 老年人的碎片依赖性睡眠依赖性记忆巩固。具体而言，研究将研究年龄是否 与睡眠相关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。睡眠在声明性和程序学习上的功能是独一无二的，每种都是相关的 具有独特的睡眠阶段和物理标记。因此，声明和程序学习将是 半探测。具体目标1将检查与年龄相关的记忆编码的变化是否有贡献 与睡眠有关的声明记忆合并。记忆的行为和神经测定 编码将进行检查。假设降低了海马参与度和编码深度 与年轻人相比降低但保留了睡眠依赖性记忆处理的年龄较大的年龄较老 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将检查与年龄相关的记忆编码的变化是否有助于 减少睡眠依赖性程序记忆巩固。假设老年人无法参与 此类任务编码时的海马，这是睡眠依赖性记忆合并至 发生。但是，假设额外的培训可以在较老的情况下产生睡眠依赖的性能益处 成年人。拟议的研究具有创新性，因为它将新颖的概念应用于认知衰老领域，并完善了 使用睡眠依赖性记忆巩固的研究方法（计算编码能力） 该领域的新技术（高深度多渗透学，fMRI），并试图改变治疗和 阿尔茨海默氏病和睡眠目标衰老的预防策略。而且，拟议的工作是 意义重大，因为它将为阿尔茨海默氏病预防和治疗的方法提供信息：如果个人 记忆编码或睡眠微观结构的差异降低了睡眠依赖性记忆处理，这些 可能是延迟阿尔茨海默氏病症状和其他形式认知能力下降的目标。