The perivascular space: A structural link between inadequate sleep, glymphatic dysfunction, and neurocognitive outcomes in adolescents

血管周围空间：青少年睡眠不足、类淋巴功能障碍和神经认知结果之间的结构联系

• 批准号: 10578466
• 负责人: Juan Andres Piantino
• 金额: $ 11.55万
• 依托单位: OREGON HEALTH & SCIENCE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-01-01 至 2024-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10578466
• 关键词: Address; Adolescence; Adolescent; Adolescent and Young Adult; Affect; Alcohols; Algorithms; Alzheimer' s disease related dementia; Area; Attention; Automobile Driving; Behavioral; Biological; Blood Vessels; Brain; Cerebrum; Child; Clinical; Clinical Research; Cohort Studies; Contrast Media; Cross-Sectional Studies; Data; Detection; Development; Disease; Ethics; Excision; Exposure to; Functional disorder; Gadolinium; Goals; Health; Health Policy; Hour; Human; Impaired cognition; Impairment; Knowledge; Link; Location; Longitudinal cohort; Magnetic Resonance Imaging; Measures; Mediating; Mediator; Memory; Methods; Morphology; Motor; National Heart, Lung, and Blood Institute; Neurocognitive; Neurocognitive Deficit; Outcome; Patient Self-Report; Patients; Pediatric Research; Performance; Personal Satisfaction; Procedures; Public Health; Recommendation; Reporting; Research; Risk; Role; Schools; Sleep; Sleep Deprivation; Sleep Disorders; Slow-Wave Sleep; Social Functioning; Students; Testing; Time; Traumatic Brain Injury; United States; Veterans; Vulnerable Populations; Wakefulness; adverse outcome; aging population; brain magnetic resonance imaging; circadian; clinical care; design; glymphatic dysfunction; glymphatic function; glymphatic system; improved; insight; interstitial; neurodevelopment; neuroimaging; new technology; poor sleep; pre-clinical; pre-clinical research; prevent; secondary analysis; sleep quality; solute; tool; twelfth grade; vehicular accident; wasting; white matter; Address; Adolescence; Adolescent; Adolescent and Young Adult; Affect; Alcohols; Algorithms; Alzheimer' s disease related dementia; Area; Attention; Automobile Driving; Behavioral; Biological; Blood Vessels; Brain; Cerebrum; Child; Clinical; Clinical Research; Cohort Studies; Contrast Media; Cross-Sectional Studies; Data; Detection; Development; Disease; Ethics; Excision; Exposure to; Functional disorder; Gadolinium; Goals; Health; Health Policy; Hour; Human; Impaired cognition; Impairment; Knowledge; Link; Location; Longitudinal cohort; Magnetic Resonance Imaging; Measures; Mediating; Mediator; Memory; Methods; Morphology; Motor; National Heart, Lung, and Blood Institute; Neurocognitive; Neurocognitive Deficit; Outcome; Patient Self-Report; Patients; Pediatric Research; Performance; Personal Satisfaction; Procedures; Public Health; Recommendation; Reporting; Research; Risk; Role; Schools; Sleep; Sleep Deprivation; Sleep Disorders; Slow-Wave Sleep; Social Functioning; Students; Testing; Time; Traumatic Brain Injury; United States; Veterans; Vulnerable Populations; Wakefulness; adverse outcome; aging population; brain magnetic resonance imaging; circadian; clinical care; design; glymphatic dysfunction; glymphatic function; glymphatic system; improved; insight; interstitial; neurodevelopment; neuroimaging; new technology; poor sleep; pre-clinical; pre-clinical research; prevent; secondary analysis; sleep quality; solute; tool; twelfth grade; vehicular accident; wasting; white matter

Project Summary The overall objective of this proposal is to define the relationship between poor sleep, glymphatic impairment, and neurocognitive function in adolescents. Insufficient sleep in adolescents is a severe health risk worldwide. In addition, poor sleep is associated with deficits in motor function, attention, memory, and impulse control, impacting adolescents in essential areas such as driving and academic functioning. Several studies have linked poor sleep with impaired neurocognitive function in adolescents. However, the biological mechanisms underlying this association remain poorly understood. One of those mechanisms may involve the glymphatic pathway, a network of perivascular spaces that support cerebral waste clearance. During wakefulness, the brain generates considerable amounts of waste, cleared at least in part via the glymphatic pathway during sleep. This waste removal is essential for the brain to function appropriately. In this proposal, we hypothesize that poor sleep leads to glymphatic dysfunction, waste accumulation, and neurocognitive dysfunction in adolescents. Recently, the number of perivascular spaces (PVS) visible on brain MRI has been proposed as a noninvasive marker of glymphatic function. Our preliminary data show increased PVS numbers in patients with poor sleep. Moreover, in a study of US Army Veterans, we have observed an association between PVS number and neurocognitive function, specifically motor performance. These initial findings suggest a role of the glymphatic pathway in the association between poor sleep and neurocognitive function. To test our hypothesis, we propose the following aims: 1) Define the association between self-reported and objective measures of sleep duration and quality on PVS burden in normal adolescents over time after adjusting for other covariates; and 2) determine the mediating effect of PVS burden in the relationship between sleep duration and quality, and neurocognitive function in adolescents. To achieve our aims, we will take advantage of novel technology developed by our group that will allow us to measure PVS in a large, longitudinal cohort of healthy adolescents and young adults. We expect to observe a direct correlation between sleep duration and PVS burden. We also expect PVS burden, indicating glymphatic dysfunction, to mediate the relation between sleep and neurocognitive function. Findings from this study will be foundational for improving our scientific knowledge of the link between poor sleep, glymphatic dysfunction, and neurocognitive outcomes in adolescents. Advancing clinical care and research for sleep in adolescents is in line with the 2021 National Heart, Lung, and Blood Institute Sleep Disorders Research Plan to "elucidate the sleep and circadian mechanisms underlying health and disease" and "develop tools and/or methods for the early prediction, and detection […] of sleep deficiency and sleep and circadian disorders in children and adolescents to promote lifelong health and wellbeing and prevent disease."

项目摘要 该提案的总体目的是定义睡眠不良，糖浆之间的关系 青少年的障碍和神经认知功能。青少年睡眠不足是严重的 全球健康风险。此外，睡眠不佳与运动功能，注意力，记忆， 以及冲动控制，影响驾驶和学术功能等重要领域的青少年。 几项研究将睡眠不佳与青少年神经认知功能受损联系在一起。但是， 该关联的基础生物学机制仍然很少了解。这些机制之一可能 涉及糖基途径，该途径是支持脑废物清除的血管周空间网络。 在清醒期间，大脑会产生大量的废物，至少部分通过 睡眠期间的胶状途径。清除这种废物对于大脑的正常运行至关重要。在这个 提案，我们假设睡眠不佳会导致糖性功能障碍，废物积累和 青少年的神经认知功能障碍。最近，可见的周围空间数量（PV） 已经提出了脑MRI作为糖性功能的无创标记。我们的初步数据显示 睡眠不佳的患者的PVS数量增加。此外，在对美国退伍军人的研究中，我们有 观察到PVS数与神经认知功能（特别是运动表现）之间存在关联。 这些最初的发现表明，糖途径在睡眠不良与睡眠之间的关联中的作用 神经认知功能。 为了检验我们的假设，我们提出以下目的：1）定义自我报告和 随着时间的推移，正常青少年的PVS的睡眠时间和质量的客观度量随着时间的推移而燃烧 调整其他协变量； 2）确定PVS Burnen在关系中的中介作用 青少年的睡眠持续时间和质量以及神经认知功能。为了实现我们的目标，我们将采取 我们小组开发的新技术的优势将使我们能够在大型， 健康青少年和年轻人的纵向队列。我们希望观察到直接相关 睡眠持续时间和PVS负担。我们还期望PVS负担表明糖性功能障碍，可以调解 睡眠与神经认知功能之间的关系。 这项研究的结果将是基本的，以提高我们对贫穷之间联系的科学知识 青少年的睡眠，糖性功能障碍和神经认知结果。推进临床护理和 青少年睡眠研究与2021年国家心脏，肺和血液研究所睡眠一致 疾病研究计划“阐明健康与疾病的昼夜节律机制” 并为早期预测开发工具和/或方法，以及对睡眠不足和睡眠的检测[…] 儿童和青少年的昼夜节律疾病，以促进终身健康和福祉并预防疾病。”