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

项目摘要 了解健康老龄化中睡眠和记忆的变化对预防和治疗老年痴呆症至关重要。 包括阿尔茨海默氏症在内的衰老疾病。阿尔茨海默病早期观察到睡眠不足 甚至可能早于老年痴呆症的发作。认知能力下降和睡眠水平下降 即使在健康的老龄化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， 这项计划的目的是了解睡眠的变化是否能解释认知能力的变化 健康的老龄化。本申请的具体目标是了解保存和 老年人睡眠依赖性记忆巩固不足。具体而言，研究将检查年龄是否- 睡眠依赖性记忆处理的相关变化反映了睡眠生理学、记忆 编码或两者。睡眠在陈述性学习和程序性学习中的作用是独特的，它们之间相互关联 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 分别探测。具体目标1将研究是否与年龄有关的变化，记忆编码有助于 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，海马参与和编码深度的减少 与年轻人相比，老年人的睡眠依赖性记忆处理减少，但保留了 成年人了第二个目的是研究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将研究与年龄相关的记忆编码变化是否有助于 减少睡眠依赖的程序性记忆巩固。据推测，老年人未能参与 海马体在这些任务的编码，睡眠依赖的记忆巩固的必要状态， 发生.然而，额外的训练被假设为在老年人中产生睡眠依赖性的表现益处。 成年人了这项研究具有创新性，因为它将一个新的概念应用于认知老化领域， 睡眠依赖性记忆巩固（考虑编码能力）的研究方法，利用 新技术（高依赖性多导睡眠图，功能磁共振成像），并寻求改变治疗和 老年痴呆症的预防策略和睡眠目标的老化。此外，拟议的工作是 重要的是，它将告知阿尔茨海默病预防和治疗的方法：如果个人 记忆编码或睡眠微结构的差异减少了睡眠依赖的记忆处理， 可能是延缓阿尔茨海默病症状和其他形式认知能力下降的靶点。

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.