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

衰老、睡眠和β-淀粉样蛋白病理学及其对记忆的影响

• 批准号: 8197973
• 负责人: BRYCE A. MANDER
• 金额: $ 5.39万
• 依托单位: UNIVERSITY OF CALIFORNIA BERKELEY
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-12-01 至 2013-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8197973
• 关键词: Age-associated memory impairment; Aging; Alzheimer' s Disease; Amyloid; Amyloid Proteins; Brain; Brain Pathology; Brain imaging; Characteristics; Clinical; Cognitive; Cognitive aging; Coupled; Deterioration; Elderly; Electroencephalography; Episodic memory; Functional Magnetic Resonance Imaging; Hippocampus (Brain); Human; Image; Impaired cognition; Impairment; Individual; Intervention; Learning; Link; Literature; Longevity; MRI Scans; Measures; Mediating; Mediation; Memory; Memory impairment; Methods; Neurodegenerative Disorders; Pathology; Pathway interactions; Physiology; Pittsburgh Compound-B; Population; Positron-Emission Tomography; Protocols documentation; Public Health; Relative (related person); Role; Senile Plaques; Sleep; Sleep Wake Cycle; Slow-Wave Sleep; Testing; Time; Tracer; Work; age related; amyloid pathology; awake; beta amyloid pathology; cohort; density; experience; healthy aging; improved; in vivo; insight; memory encoding; memory process; non rapid eye movement; novel; public health relevance; young adult

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.

描述（由申请人提供）：老年人的睡眠受到干扰，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逐渐受损。在过去的十年里，已有的文献表明，睡眠，尤其是深度睡眠睡眠，对于支持新情景记忆的学习和保留至关重要。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。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，2-淀粉样蛋白的皮质积聚预示着健康老龄化和阿尔茨海默病的情景记忆衰退。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，并且睡眠不足会导致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衰老的一个重要但尚未表征的特征，代表使用已知增强 SWS 的现有方法的新治疗目标。该提案将 2-淀粉样蛋白的体内脑成像 (PIB-PET) 与睡眠的高密度脑电图测量和情景学习的次日脑成像 (fMRI) 相结合，旨在表征 2-淀粉样蛋白与睡眠之间的关系，并将检查它们对大脑功能和情景学习能力的综合影响。 公共健康相关性：该提案将 2-淀粉样蛋白的体内脑成像 (PIB-PET) 与睡眠的高密度脑电图测量和情景学习的次日脑成像 (fMRI) 相结合，旨在描述晚年睡眠改变、记忆受损和 2-淀粉样蛋白脑病理学之间的关系。这些研究探讨了一种可以促进健康老龄化的新途径，为老年人口提供实质性的临床、社会和公共卫生优势。