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，以非快速眼动（NREM）慢波睡眠（SWS）减少最为突出。与睡眠改变同时发生的是衰老的认知标志；在形成和保持新的情景记忆的能力上的渐进性损害。在过去的十年里，已有的文献表明，睡眠，尤其是SWS，对于支持学习和保留新的情景记忆至关重要。然而，与年龄相关的睡眠变化与晚年认知记忆衰退之间的关系仍然知之甚少。在以后的生活中，中枢2-淀粉样蛋白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2-淀粉样蛋白的形成预示着健康衰老和阿尔茨海默病的情景记忆衰退。此外，与2-淀粉样蛋白积累最多相关的皮质区域与已知产生SWS的皮质区域重叠。此外，研究表明，大脑中2-淀粉样蛋白的浓度与睡眠-觉醒周期紧密相关，睡眠不足会导致2-淀粉样蛋白斑块的增加。如果正确的话，SWS和2-淀粉样蛋白之间的关系将代表一个重要的，但尚未被描述的认知衰老特征，代表使用已知的现有方法来增强SWS的新治疗靶点。结合体内2-淀粉样蛋白脑成像（PIB-PET）、高密度睡眠脑电图和第二天情景学习脑成像（fMRI），本研究旨在描述2-淀粉样蛋白与睡眠之间的关系，并将研究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. PUBLIC HEALTH RELEVANCE: 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 altered sleep, impaired memory, and 2-amyloid brain pathology in later life. These studies examine a novel pathway by which healthy aging may be promoted, affording substantive clinical, societal and public health advantages for older adult populations.