Cortical Hemodynamism and Oxygenation During Sleep and Cognition: Window to Cognitive Impairment and Neurodegeneration in Aging

项目摘要 我的长期目标是成为“衰老和睡眠医学”领域的一流内科医生和科学家。 神经退行性疾病。“具体地说，我的目标是成为开发创新方法的领先专家 用于老年人的睡眠和睡眠障碍呼吸(SDB)评估和伴随的认知，以便 更好地了解神经退行性疾病。关于睡眠、SDB和认知的调查报告 老年人将是我作为内科科学家职业发展的基础。 老年人的睡眠和SDB特征不足，特别是在进展的背景下 从正常衰老到轻度认知障碍(MCI)再到痴呆症。这部分是因为目前 由于缺乏关于皮质血流动力学或睡眠的信息，对睡眠的评估有限 充氧以捕捉SDB的睡眠碎片或皮质缺氧。因此，同时与 功能神经影像监测皮质血流动力学和氧合的同步记录 PSG将大大有助于我们理解衰老对睡眠的影响及其后续 对认知能力下降和/或神经退化的影响。较新的技术，如近红外 光谱学(NIR)有可能显著提高同时获取 与PSG同步记录脑血流动力学和氧合，以便更好地了解 睡眠和SDB期间衰老对大脑功能的影响。 我建议的项目将是在睡眠期间同时进行近红外光谱和PSG，以及认知测试 有SDB和没有SDB的老年人。我的目标是确定潜在的睡眠生物标记物在血液动力学或 SDB和睡眠本身的氧合模式，这将成为我未来纵向研究的基础 检查睡眠结构和相关的大脑功能在多大程度上可以作为有效的预测因子 认知衰退、MCI和神经退行性疾病。 基于我之前接受的睡眠医学和神经科医生的培训，我的职业发展计划是获得 实现这一职业目标所需的其他技能。我的指导团队将在1)指导我的训练 结合NIRS和PSG评估潜在睡眠的脑功能；2)其他形式的功能 神经成像；3)功能神经成像技术分析；4)认知功能表征，MCI 5)了解神经退行性疾病的病理生理学和相关的 合并症；以及6)横断面和纵向数据的方法和统计方法，以及 分析影响睡眠和衰老的内科/精神科合并症和药物。

Project Summary My long-term goal is to become a leading physician-scientist in the field of “sleep medicine in aging and neurodegenerative disorders.” Specifically, I aim to become a leading expert in developing innovative methods for sleep and sleep-disordered breathing (SDB) evaluation and concomitant cognition in older adults in order to better understand neurodegenerative disorders. The proposed investigation of sleep, SDB and cognition in older adults will be the basis for my career development as a physician scientist. Sleep and SDB are under-characterized in older adults, particularly in the context of the progression from normal aging to Mild Cognitive Impairment (MCI) to dementia. This is partially because current assessments of sleep are limited due to the lack of information regarding cortical hemodynamism or oxygenation to capture sleep fragmentation or cortical hypoxia from SDB. Thus, simultaneous and synchronized recording of functional neuroimaging monitoring cortical hemodynamism and oxygenation with PSG would substantially contribute to our understanding of the effect of aging on sleep and its subsequent impact on cognitive decline and/or neurodegeneration. Newer technologies such as Near Infrared Spectroscopy (NIRS) have the potential to significantly improve the ability to acquire simultaneous synchronized recording of brain hemodynamism and oxygenation with PSG in order to better understand the aging effects on brain function during sleep and SDB. The project I propose will be to conduct simultaneous NIRS and PSG during sleep, and cognitive tests on older adults with SDB and without SDB. I aim to identify potential sleep biomarkers in hemodynamism or oxygenation patterns from SDB and sleep itself, which will form the basis for my future longitudinal study to examine the extent to which sleep architecture and associated brain function can serve as potent predictors of cognitive decline, MCI and neurodegenerative disorders. Building on my prior training as a Sleep MD and Neurologist, my career development plan is to gain the necessary additional skills to achieve this career goal. My mentorship team will guide my training in 1) combining NIRS with PSG to assess the brain function underlying sleep; 2) other modalities of functional neuroimaging; 3) analysis of functional neuroimaging technologies; 4) characterizing cognitive function, MCI and dementia; 5) understanding the pathophysiology of neurodegenerative disorders and associated comorbidities; and 6) methodological and statistical approaches to cross-sectional and longitudinal data, and analysis of medical/psychiatric comorbidities and medications that impact sleep and aging.