Tai Chi Practice and Sleep-Active Glymphatic Function

太极拳练习和睡眠活跃类淋巴功能

• 批准号: 10583904
• 负责人: Jeffrey J Iliff
• 金额: $ 49.38万
• 依托单位: SEATTLE INST FOR BIOMEDICAL/CLINICAL RES
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-01-01 至 2024-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10583904
• 关键词: Abeta clearance; Abeta synthesis; Affective; Alzheimer disease prevention; Alzheimer' s Disease; Alzheimer' s disease model; Alzheimer' s disease pathology; Alzheimer' s disease related dementia; Alzheimer’s disease biomarker; Amyloid beta-Protein; Beds; Behavior; Biological Markers; Blood Vessels; Brain; Breathing; Cardiovascular Physiology; Cerebrospinal Fluid; Cerebrovascular Disorders; Chinese; Chronic; Clinical; Clinical Research; Clinical Trials; Cognition; Cognitive; Dementia; Deposition; Development; Disease; Elderly; Enrollment; Equilibrium; Failure; Foundations; Frequencies; Functional Magnetic Resonance Imaging; Future; Goals; Human; Individual; Intercellular Fluid; Intervention; Intervention Trial; Longitudinal Studies; Magnetic Resonance Imaging; Measurable; Measurement; Measures; Modality; Moods; Motion; Movement; Outcome; Participant; Pathologic; Pathway interactions; Patient Self-Report; Physical activity; Physiological; Physiological Processes; Pilot Projects; Polysomnography; Posture; Prevention; Primary Prevention; Proteins; Questionnaires; Respiration; Respiratory physiology; Risk; Self Assessment; Senile Plaques; Sleep; Sleep Apnea Syndromes; Sleep Fragmentations; Sleep disturbances; Symptoms; Tai Ji; Testing; Training; Vasomotor; Ventricular; Veterans; Water; Well in self; aging brain; blood oxygen level dependent; cerebrospinal fluid flow; contrast enhanced; cost; demented; experience; glymphatic clearance; glymphatic dysfunction; glymphatic function; glymphatic system; improved; improvement on sleep; interest; interstitial; middle age; mindfulness; mouse model; multimodality; novel strategies; pressure; prevent; prospective; randomized, clinical trials; recruit; response; secondary analysis; sleep quality; solute; study population; tau Proteins; wasting

PROJECT SUMMARY/ABSTRACT Amyloid plaque deposition, a key pathological hallmark of Alzheimer’s disease (AD), begins 1-2 decades before manifestation of clinical symptoms of dementia. Among cognitively intact individuals and in AD’s most prevalent sporadic form, the production of amyloid-β (Aβ) does not change, while clearance of Aβ is slowed, indicating that the failure of Aβ clearance may underlie the development of AD pathology and that interventions that improve its clearance may provide an opportunity for primary prevention of AD. Over the past 10 years, our group has helped to define the ‘glymphatic system’, a brain-wide network of perivascular pathways along which cerebrospinal fluid (CSF) surrounding the brain exchanges with brain interstitial fluid, supporting the clearance of interstitial wastes, including Aβ and tau. Impairment of glymphatic clearance is observed in the aging brain and in mouse models of AD. Thus, improving glymphatic clearance of brain interstitial proteins may be one approach to preventing the development of AD. Glymphatic function is regulated by sleep-wake behavior, with faster clearance occurring during sleep. Tai Chi is a Chinese martial art focusing on mindful body movement, posture, and breathing as an avenue to achieve a state of internal balance, calm, and clarity. In clinical studies, practice of Tai Chi is associated with improved sleep quality, cognition, mood, cardiovascular and respiratory function, and balance/physical activity. However, the physiological processes underlying the cognitive and affective effects of Tai Chi remain undefined. We hypothesize that Tai Chi practice improves glymphatic function. To test this hypothesis, we will enroll 75 middle-aged (50-70 years) participants with different levels of Tai Chi practice experience: Tai Chi proficients (10+ year of practice, n=25), Tai Chi beginners (12 months practice, n=25) and Tai Chi naïve participants (n=25). We will 1) examine the association between Tai Chi practice and glymphatic function using multi-modal magnetic resonance imaging (MRI) using contrast-enhanced MRI, T1/FLAIR assessment of MRI-visible perivascular spaces, intravoxel incoherent motion, and fast BOLD-fMRI; 2) examine relationships between Tai Chi practice and sleep, including sleep fragmentation, efficiency, and duration, assessed by self-reported questionnaires and objective measurements of sleep duration, fragmentation and efficiency using a bed pressure mat. We will examine the relationship between sleep measures and MRI-assessed glymphatic function. The ultimate goal of this study is to elucidate mechanisms of Tai Chi practice in prevention of AD and related dementias. This pilot study will determine whether long-term Tai Chi practice is associated with physiological changes in glymphatic function and sleep. If we find cross-sectional association among Tai Chi practice, glymphatic function, and sleep, in the future we will investigate whether these changes are associated with duration of Tai Chi practice and whether these changes are associated with changes in AD biomarkers in a longitudinal study or in a prospective randomized clinical trial.

项目总结/摘要 淀粉样斑块沉积是阿尔茨海默病（AD）的一个关键病理标志， 在痴呆临床症状出现之前。在认知完整的个体中， 散发型，β淀粉样蛋白（Aβ）的产生没有变化，而Aβ的清除减慢， 表明Aβ清除的失败可能是AD病理学发展的基础， 提高其清除率可能为AD的一级预防提供机会。在过去的10年里， 我们的小组帮助定义了“胶质淋巴系统”，一个由血管周围通路组成的全脑网络沿着 其中脑周围的脑脊液（CSF）与脑间质液交换，支持脑内的 清除间质废物，包括Aβ和tau。胶质淋巴清除的损害是观察到的 老化的大脑和AD的小鼠模型。因此，改善脑间质蛋白的胶质淋巴清除可能 是预防AD发展的一种方法。淋巴功能受睡眠-觉醒调节 行为，在睡眠期间发生更快的清除。太极是一种专注于意念的中国武术 身体运动，姿势和呼吸作为达到内部平衡，平静和清晰状态的途径。 在临床研究中，太极拳的练习与改善睡眠质量，认知，情绪， 心血管和呼吸功能以及平衡/体力活动。然而，生理过程 太极的认知和情感影响的基础仍然不明确。我们假设太极拳练习 改善胶质淋巴功能。为了验证这一假设，我们将招募75名中年（50-70岁）参与者 具有不同太极拳练习经验水平：太极拳熟练者（10年以上练习，n=25），太极拳 初学者（12个月的练习，n=25）和太极天真的参与者（n=25）。我们将1）检查 多模态磁共振成像研究太极拳练习与淋巴功能之间的关系 (MRI)使用对比增强MRI，MRI可见血管周围间隙的T1/FLAIR评估，体素内 不连贯的运动，和快速BOLD-fMRI; 2）研究太极练习和睡眠之间的关系， 包括睡眠碎片，效率和持续时间，通过自我报告的问卷和客观评估 使用床压垫测量睡眠持续时间、碎片和效率。我们会研究 睡眠测量和MRI评估的胶质淋巴功能之间的关系。本研究的最终目的是 阐明太极拳练习预防AD及相关痴呆的机制。这项试点研究将 确定长期太极练习是否与淋巴功能的生理变化有关 睡觉如果我们发现太极拳练习，胶质淋巴功能和睡眠之间的横截面联系， 未来，我们将调查这些变化是否与太极拳练习的持续时间有关， 这些变化与纵向研究或前瞻性研究中AD生物标志物的变化相关。 随机临床试验。