Aging, sleep, and beta-amyloid pathology and their impact on memory

描述（由申请人提供）：老年人经历睡眠中断，其中非快速眼动（NREM）慢波睡眠（SWS）的减少最为突出。与睡眠改变并行的是衰老的认知标志;形成和保留新情景记忆的能力的进行性损伤。在过去的十年里，一个成熟的文献现在表明，睡眠，特别是SWS，是支持学习和保留新的情景记忆的关键。然而，与年龄相关的睡眠改变和晚年认知记忆下降之间的关系仍然知之甚少。中枢2-淀粉样蛋白在晚年的积累代表了睡眠和记忆这两个因素之间的潜在联系。具体来说，皮质中2-淀粉样蛋白的积累可以预测健康老年人和阿尔茨海默病患者的情景记忆衰退。此外，与2-淀粉样蛋白最大积累相关的皮质区域与已知产生SWS的皮质区域重叠。此外，已经证明大脑中2-淀粉样蛋白的浓度与睡眠-觉醒周期紧密相关，并且睡眠不足导致2-淀粉样蛋白斑块的存在增加。如果正确的话，SWS和2-淀粉样蛋白之间的这种关系将代表认知老化的一个重要但尚未表征的特征，代表一种使用已知增强SWS的现有方法的新治疗靶点。结合2-淀粉样蛋白的体内脑成像（PIB-PET）与睡眠的高密度EEG测量和情景学习的次日脑成像（fMRI），该提议旨在表征2-淀粉样蛋白和睡眠之间的关系，并将检查它们对脑功能和情景学习能力的综合影响。

DESCRIPTION (provided by applicant): Older adults experience disrupted sleep, with reductions in non-rapid eye movement (NREM) slow-wave sleep (SWS) being most prominent. In parallel with alterations of sleep is the cognitive hallmark of aging; a progressive impairment in the ability to form and retain new episodic memories. Within the last ten years, an established literature now suggests that sleep, particularly SWS, is critical for supporting the learning and retention of new episodic memories. Nevertheless, the relationship between age-related alterations of sleep and cognitive memory decline in later life remains poorly understand. The accumulation of central 2- amyloid in later life represents a potential link between these two factors of sleep and memory. Specifically, cortical build-up of 2-amyloid predicts episodic memory decline in healthy aging and Alzheimer's disease. Further, cortical regions associated with the greatest accumulation of 2-amyloid overlap with the cortical regions known to generate SWS. Moreover, it has been demonstrated that brain concentrations of 2- amyloid are tightly coupled to the sleep-wake cycle, and that sleep loss results in an increased presence of 2-amyloid plaques. If correct, this relationship between SWS and 2-amyloid would represent an important, but as yet uncharacterized, feature of cognitive aging, representing a novel treatment target using already existing methods known to enhance SWS. Combining in vivo brain imaging of 2-amyloid (PIB-PET) with high-density EEG measures of sleep and next day brain imaging (fMRI) of episodic learning, this proposal aims to characterize the relationship between 2-amyloid and sleep, and will examine their combined effects on brain function and episodic learning ability.