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”领域的领先医生兼科学家。 神经退行性疾病”具体来说，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呼吸障碍（SDB）评估和伴随认知， 更好地了解神经退行性疾病。对睡眠、睡眠障碍和认知的拟议调查， 老年人将是我作为一名医生科学家的职业发展的基础。 睡眠和SDB在老年人中的特征不足，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。部分原因是，目前 由于缺乏关于皮质血流动力学的信息， 氧合以捕获来自SDB的睡眠碎片或皮质缺氧。同时， 同步记录功能性神经成像监测皮质血流动力学和氧合， PSG将大大有助于我们了解衰老对睡眠的影响及其后续影响。 对认知能力下降和/或神经退化的影响。近红外等新技术 近红外光谱（NIRS）有可能显着提高同时获得的能力， 同步记录脑血流动力学和氧合与PSG，以便更好地了解 衰老对睡眠和睡眠障碍期间大脑功能的影响。 我建议的项目将是在睡眠期间同时进行NIRS和PSG以及认知测试 对患有SDB和未患有SDB的老年人的影响。我的目标是确定血液动力学中潜在的睡眠生物标志物， 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， 研究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。 基于我之前作为睡眠医学博士和神经学家的培训，我的职业发展计划是获得 需要更多的技能来实现这一职业目标。我的导师团队将在1） 结合NIRS和PSG评估睡眠相关的脑功能; 2）其他功能模式 神经影像学; 3）功能性神经影像学技术分析; 4）表征认知功能，MCI 和痴呆症; 5）了解神经退行性疾病和相关疾病的病理生理学 合并症;和6）横断面和纵向数据的方法学和统计学方法，以及 分析影响睡眠和衰老的医学/精神科共病和药物。

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.