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

描述(申请人提供)：老年人睡眠受到干扰，其中非快速眼动(NREM)慢波睡眠(SWS)的减少最为明显。与睡眠变化平行的是衰老的认知特征；形成和保持新的情节记忆的能力的进行性损害。在过去的十年里，一份成熟的文献现在表明，睡眠，特别是短暂性睡眠障碍，对于支持学习和保持新的情节记忆至关重要。然而，与年龄相关的睡眠改变与晚年认知记忆下降之间的关系仍然知之甚少。中央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。具体地说，皮质中2-淀粉样蛋白的积聚预测了健康老龄化和阿尔茨海默病患者的间歇性记忆衰退。此外，与2-淀粉样蛋白积聚最多相关的皮质区域与已知的产生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-觉醒周期密切相关，睡眠不足会导致2-淀粉样蛋白斑块的存在增加。如果正确，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确定的特征，代表了使用现有方法增强SWS的新治疗靶点。将2-淀粉样蛋白的活体脑成像(PIB-PET)与高密度脑电睡眠测量和情景学习的次日脑成像(FMRI)相结合，旨在表征2-淀粉样蛋白与睡眠的关系，并将检验它们对大脑功能和情景学习能力的联合影响。 公共卫生相关性：结合体内2-淀粉样脑成像(PIB-PET)和高密度脑电睡眠测量以及间歇性学习的次日脑成像(FMRI)，该建议旨在表征睡眠改变、记忆受损和老年2-淀粉样脑病理之间的关系。这些研究考察了一种可促进健康老龄化的新途径，为老年人口提供了实质性的临床、社会和公共卫生优势。

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.