Sleep, breathing, hemodynamic oscillations, and cerebrospinal fluid movements - Building toward a novel treatment approach for Alzheimer's disease

睡眠、呼吸、血流动力学振荡和脑脊液运动——构建阿尔茨海默病的新型治疗方法

• 批准号: 10740443
• 负责人: AMY J SCHWICHTENBERG
• 金额: $ 19万
• 依托单位: PURDUE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-09-01 至 2025-05-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10740443
• 关键词: Adult; Alzheimer' s Disease; American; Amyloid beta-Protein; Animals; Behavior; Biological; Blood; Blood Circulation; Brain; Breathing; Cardiac; Cerebrospinal Fluid; Cerebrovascular Circulation; Circulation; Clinical Trials; Coupled; Coupling; Cues; Diagnosis; Frequencies; Functional Magnetic Resonance Imaging; Goals; Human; Individual; Intervention; Knowledge; Link; Measures; Meditation; Movement; Nerve Degeneration; Neurodegenerative Disorders; Neurons; Outcome; Participant; Pathology; Pathway interactions; Pattern; Physiological; Physiological Processes; Pilot Projects; Process; Quality of life; Research; Respiration; Sampling; Scanning; Signal Transduction; Sleep; Sleep Deprivation; Sleep Disorders; Sleep Stages; Slow-Wave Sleep; System; Testing; Tissues; Variant; Visual; Wakefulness; Work; abeta accumulation; awake; cerebral blood volume; cranium; fluid flow; glymphatic system; hemodynamics; high reward; improved; individual variation; magnetic resonance imaging/electroencephalography; middle age; non rapid eye movement; novel; pressure; tau Proteins; wasting

Sleep, breathing, hemodynamic oscillations, and cerebrospinal fluid movements – Building toward a novel treatment approach for Alzheimer's disease Sleep deficiencies/problems are common in Alzheimer's disease with several hypothesized connections to the movement of cerebral spinal fluid (CSF) in the brain. For example, within Alzheimer's disease the accumulation of beta-amyloid and tau proteins may reflect inefficiencies in neuro-metabolic waste clearance during sleep (a glymphatic system process that is intricately linked with CSF movement). Within neurodegenerative research, the circulation of CSF has hypothesized links to several biological/physiological processes (e.g., sleep, hemodynamic oscillations, breathing); however, we are limited in our understanding of how to potentially improve CSF movement and neuro-metabolic waste clearance to ultimately slow the progression of Alzheimer's disease. The present study fills these critical gaps by (1) quantifying sleep-coupled CSF movement and (2) documenting how CSF movement is coupled with other (more easily assessed and manipulated) biological signals (i.e., hemodynamic oscillations, breathing). The overarching goals of this line of work are to improve our understanding of CSF movement and how this knowledge can be leveraged to slow the progression of Alzheimer's disease. Unlike blood circulation, CSF has no `engine' to drive its flow; therefore, changes in cerebral blood volume (CBV) likely serve as a `driver' of CSF movement. Previous research demonstrates that increases in CBV can be neuronally driven (e.g., sleep); arterial pulsation driven; or breath driven (e.g., meditation/guided breathing). However, we do not understand the magnitude of these changes/couplings. Improving CSF movement/circulation for individuals with Alzheimer's disease has the potential to slow the pathology progression and could prolong higher quality of life for the millions of Americans currently diagnosed.  Aim 1: Assess the degree of coupling between cerebral blood volume (CBV) and cerebral spinal fluid (CSF) movement during wake and sleep states.  Aim 2: Assess the relative contributions of breathing oscillations on CBV and CSF fluctuations during wake and sleep states.

睡眠，呼吸，血液动力学振荡和脑脊液运动 - 朝向 阿尔茨海默氏病的新型治疗方法 睡眠不足/问题在阿尔茨海默氏病中很常见，有几个假设的联系 大脑中脑脊髓液（CSF）的运动。例如，在阿尔茨海默氏病中 β-淀粉样蛋白和tau蛋白的积累可能反映出神经代谢清除的效率低下 在睡眠期间（一种与CSF运动相关的胶囊系统过程）。之内 神经退行性研究，CSF的循环已经假设与几种生物学/生理学的联系 过程（例如睡眠，血液动力学振荡，呼吸）；但是，我们对我们的理解有限 如何潜在地改善CSF运动和神经代谢的废物清除率，以最终减慢 阿尔茨海默氏病的进展。本研究通过（1）量化睡眠耦合来填补这些关键空白 CSF运动和（2）CSF运动如何与其他CSF运动（更容易评估）和 操纵）生物信号（即血液动力学振荡，呼吸）。这条线的总体目标 工作是提高我们对CSF运动的理解，以及如何利用这些知识来减慢 阿尔茨海默氏病的进展。 与血液循环不同，CSF没有“发动机”来推动其流动。因此，脑血容量的变化 （CBV）可能是CSF运动的“驱动力”。先前的研究表明，CBV的增加可以 被神经元素驱动（例如睡眠）；动脉搏动驱动；或呼吸驱动（例如，冥想/引导呼吸）。 但是，我们不了解这些变化/耦合的大小。改善CSF 阿尔茨海默氏病个体的运动/循环有可能减慢病理的进展 并可以延长目前被诊断出的数百万美国人的生活质量。 目标1：评估脑血容量（CBV）和脑脊髓液之间的耦合程度 （CSF）在唤醒和睡眠状态下运动。 目标2：评估呼吸振荡对CBV和CSF波动的相对贡献 唤醒和睡眠状态。