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、血流动力学振荡和脑脊液运动--朝着 阿尔茨海默病的新治疗方法 睡眠不足/问题在阿尔茨海默病中很常见，并有几个假设的联系 与脑脊液(CSF)在大脑中的运动有关。例如，在阿尔茨海默病中， β-淀粉样蛋白和tau蛋白的积累可能反映了神经代谢废物清除的低效。 在睡眠期间(一种与脑脊液运动错综复杂地联系在一起的淋巴系统过程)。在 神经退行性研究认为，脑脊液的循环与几种生物/生理因素有关 过程(例如，睡眠、血流动力学振荡、呼吸)；然而，我们对 如何潜在地改善脑脊液的运动和神经代谢废物的清除，以最终减缓 阿尔茨海默病的进展。目前的研究通过(1)量化睡眠耦合来填补这些关键的空白 脑脊液运动和(2)记录脑脊液运动如何与其他(更容易评估和 操纵)生物信号(即，血流动力学振荡、呼吸)。这条线路的首要目标是 工作是提高我们对脑脊液运动的理解，以及如何利用这种知识来减缓 阿尔茨海默病的进展。 与血液循环不同，脑脊液没有驱动其流动的“引擎”；因此，脑血量的变化 (CBV)可能是脑脊液运动的“驱动力”。先前的研究表明，CBV的增加可以 神经驱动(如睡眠)、动脉搏动驱动或呼吸驱动(如冥想/引导呼吸)。 然而，我们并不了解这些变化/联结的规模。改善脑脊液 阿尔茨海默病患者的运动/循环有可能减缓病理进展 并可能延长目前确诊的数百万美国人的更高生活质量。 目标1：评估脑血容量和脑脊液之间的耦合程度 (脑脊液)清醒和睡眠状态下的运动。 目标2：评估呼吸振荡对脑血流量和脑脊液波动的相对贡献 唤醒和睡眠状态。