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

项目摘要/摘要 阿尔茨海默病是美国主要的死亡原因，其患病率预计将从近 今天的600万到2050年的1300万美国人。众所周知，睡眠障碍是与年龄相关的风险因素 认知功能减退和阿尔茨海默病的发展。努力了解两者之间的联系 睡眠和阿尔茨海默氏症一直专注于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内稳态在记忆加工中的作用。一个 睡眠记忆功能的关键过程是一种记忆重演，在此过程中，神经元序列 活动重复并复制反映记忆觉醒状态的模式。我的研究团队一直专注于 识别构成记忆重放的神经元通讯元件，以及其中的几个 元素可以从简单的表面脑电(EEG)中观察到。慢波，theta爆发，以及 睡眠纺锤体标记记忆重放周期的时间，并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 为努力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 Theta猝发的变化与老年人的认知能力下降有关，并可能预测未来 拒绝。我的总体目标是填补睡眠和记忆重播之间联系的知识空白 有助于指导阿尔茨海默病发病机制的新诊断和干预研究 阿尔茨海默氏症的治疗方法。我的主要假设是，theta爆发式脑电功率的变化 与老年人的认知能力下降有关。我的研究目标是确定 在与年龄相关的认知衰退的背景下，theta爆发式脑电功率和认知变化之间的关系 为未来生物标记物的开发和早期阿尔茨海默病的病因/机制研究奠定基础。这就做 通过追求以下具体目标来实现这些目标：目标1a)确定 Theta爆发力发生在经历认知衰退的老年成年人中，目标1b)决定是否改变 老年人的认知分数和基线theta爆发力是未来的有效预测因子 认知衰退和目标2)决定了theta爆发大小和theta爆发时间排列的贡献 对观察到的爆发性脑电能量的降低。我提出的实验具有创新性，因为它们 是第一个研究theta爆发式变化和认知老化之间关系的人。我的建议是 意义重大，因为它将加深我们对睡眠神经保护属性的理解，并将促进 一种临床工具，可以作为生物标记物和治疗靶点来衡量关键神经元功能的完整性。

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.