A Breakdown of Memory Replay: Elucidating the Relationship Between Sleep and Alzheimer's Disease from Surface Electroencephalography

记忆回放的分解：从表面脑电图阐明睡眠与阿尔茨海默病之间的关系

• 批准号: 10569304
• 负责人: Brice V McConnell
• 金额: $ 15.55万
• 依托单位: UNIVERSITY OF COLORADO DENVER
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-06-01 至 2025-02-28
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10569304
• 关键词: Adult; Age; Age-associated memory impairment; Aging; Alzheimer' s Disease; Alzheimer' s disease model; Alzheimer' s disease pathology; Alzheimer' s disease related dementia; Alzheimer' s disease risk; Alzheimer' s disease therapy; Alzheimer’s disease biomarker; American; Biological Markers; Brain; Cause of Death; Clinical; Cognition; Cognitive; Cognitive aging; Communication; Data; Data Set; Dementia; Deterioration; Development; Early Diagnosis; Electroencephalography; Elements; Etiology; Event; Foundations; Future; Goals; Hippocampus; Home; Homeostasis; Impaired cognition; Intervention; Knowledge; Measures; Memory; Methodology; Methods; Modeling; Monitor; Neurodegenerative Disorders; Neurons; Pathogenesis; Pattern; Physiological; Physiology; Pre-Clinical Model; Prevalence; Process; Property; Regression Analysis; Regulation; Reporting; Research; Risk; Risk Factors; Role; Sleep; Sleep Deprivation; Sleep disturbances; Slow-Wave Sleep; Surface; Synapses; Testing; Visit; age related; biomarker development; cognitive change; cognitive performance; experience; experimental study; follow-up; improved; innovation; memory consolidation; memory process; neuronal patterning; neurophysiology; neuroprotection; new therapeutic target; novel; novel diagnostics; predictive marker; restoration; screening; sleep spindle; tool; treatment response; wearable device

PROJECT SUMMARY/ABSTRACT Alzheimer's disease is a leading cause of death in the U.S., and its prevalence is expected to climb from nearly 6 million today to 13 million Americans by 2050. Sleep disruption is known to be a risk factor for age-associated cognitive decline and for the development of Alzheimer's disease. Efforts to understand the connections between sleep and Alzheimer's disease have focused on key neuroprotective aspects of slow wave sleep, including its role in memory processing via regulation of synaptic remodeling and restoration of synaptic homeostasis. A critical process in sleep's memory functions is a form of memory replay, during which sequences of neuronal activity repeat and reproduce patterns that mirror the wake state of memory. My research team has focused on the identification of the neuronal communication elements that constitute memory replay, and several of these elements are observable from simple surface electroencephalography (EEG). Slow waves, theta bursts, and sleep spindles mark the timing of memory replay cycles, and understanding their role in cognitive aging and Alzheimer's disease may offer a novel method to detect and/or predict neurodegenerative disease, as well as provide a target for efforts to restore the neuroprotective properties of sleep. Our preliminary results suggest that changes in theta bursts are associated with cognitive decline among aging adults and may also predict future decline. My overall goal is to fill knowledge gaps in the connections between memory replay of sleep and Alzheimer's disease pathogenesis to help guide the development of novel diagnostics and interventional approaches for Alzheimer's disease. My overarching hypothesis is that changes in theta burst EEG power are associated with cognitive decline among aging adults. My research objectives are to determine the relationships between theta burst EEG power and cognitive changes in the context of age-associated cognitive decline as the basis for future biomarker development and causation/mechanistic studies in early Alzheimer's disease. I will accomplish these objectives by pursuing the following Specific Aims: Aim 1a) Determine whether changes in theta burst power occur in aging adults who experience cognitive decline, Aim 1b) Determine whether changes in cognitive scores and baseline theta burst power among aging adults serve as an effective predictor of future cognitive decline, and Aim 2) Determine the contribution of theta burst size and theta burst temporal alignment to the reductions in observed theta burst EEG power. My proposed experiments are innovative because they are the first to examine the relationships between theta burst changes and cognitive aging. My proposal is significant because it will further our understanding of the neuroprotective properties of sleep and will advance a clinical tool that may measure the integrity of critical neuronal functions as a biomarker and treatment target.

项目总结/摘要 阿尔茨海默病是美国的主要死因，其流行率预计将从近 到2050年将达到1300万。众所周知，睡眠中断是与年龄相关的 认知能力下降和阿尔茨海默病的发展。努力去理解 睡眠和阿尔茨海默病的研究集中在慢波睡眠的关键神经保护方面，包括其 通过调节突触重塑和恢复突触稳态在记忆处理中的作用。一 睡眠记忆功能中的一个关键过程是记忆重放的一种形式，在此期间，神经元的序列 活动重复和复制反映记忆清醒状态的模式。我的研究团队专注于 识别构成记忆重放的神经元通信元件，以及其中的几个 这些元素可以从简单的表面脑电图（EEG）中观察到。慢波θ波爆发 睡眠纺锤波标志着记忆重放周期的时间，了解它们在认知老化和 阿尔茨海默病可能提供一种新的方法来检测和/或预测神经退行性疾病，以及 为恢复睡眠的神经保护特性提供了一个目标。我们的初步结果表明， θ波爆发的变化与老年人的认知能力下降有关， 下降我的总体目标是填补睡眠的记忆回放和睡眠的记忆回放之间的联系的知识空白。 阿尔茨海默病的发病机制，以帮助指导新的诊断和干预的发展 治疗阿尔茨海默病的方法我的首要假设是，θ波脑电功率的变化是 与老年人认知能力下降有关。我的研究目标是确定 在与年龄相关的认知能力下降的背景下， 为未来生物标志物的发展和早期阿尔茨海默病的病因/机制研究奠定了基础。我会 通过追求以下具体目标来实现这些目标：目标1a）确定 θ爆发功率发生在经历认知能力下降的老年人中，目的1b）确定是否改变 老年人的认知得分和基线θ爆发力可以有效预测未来 认知能力下降，目标2）确定θ波爆发大小和θ波爆发时间对齐的贡献 与观察到的θ波脑电功率的降低有关。我提出的实验是创新的，因为它们 是第一个研究theta爆发变化和认知老化之间关系的人。我的建议是 重要的是，它将进一步加深我们对睡眠的神经保护特性的理解， 一种临床工具，可以测量关键神经元功能的完整性作为生物标志物和治疗靶点。