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

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."

项目概要 该提案的总体目标是定义睡眠不佳、类淋巴系统功能障碍之间的关系 青少年睡眠不足是一个严重的问题。 此外，睡眠不佳与运动功能、注意力、记忆力缺陷有关。 和冲动控制，影响青少年的驾驶和学业功能等重要领域。 多项研究已将青少年睡眠不良与神经认知功能受损联系起来。 这种关联背后的生物学机制仍然知之甚少，其中一种机制可能是这样的。 涉及类淋巴通路，这是一种支持脑废物清除的血管周围空间网络。 清醒时，大脑会产生大量废物，至少部分通过 睡眠期间的类淋巴通路的清除对于大脑的正常运作至关重要。 建议，我们认为睡眠不佳会导致类淋巴功能障碍、废物积累和 最近，青少年的神经认知功能障碍中可见血管周围间隙（PVS）的数量。 我们的初步数据显示，脑部 MRI 已被提议作为类淋巴功能的无创标记。 此外，在一项针对美国退伍军人的研究中，我们发现睡眠不佳的患者的 PVS 数量增加。 观察到 PVS 数与神经认知功能（特别是运动表现）之间的关联。 这些初步研究结果表明，类淋巴通路在睡眠不良和睡眠障碍之间的关联中发挥着重要作用。 神经认知功能。 为了检验我们的假设，我们提出以下目标：1）定义自我报告和 客观衡量正常青少年睡眠持续时间和质量对 PVS 负担的影响 调整其他协变量；2) 确定 PVS 负担在两者关系中的中介作用 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，我们将采取措施。 我们团队开发的新技术的优势使我们能够在大范围内测量 PVS， 我们期望观察健康青少年和年轻人之间的直接相关性。 我们还预计，PVS 负担（表明类淋巴功能障碍）会介导这一现象。 睡眠与神经认知功能的关系。 这项研究的结果将为提高我们对贫困人口之间联系的科学认识奠定基础。 促进青少年的睡眠、类淋巴功能障碍和神经认知结果。 青少年睡眠研究与 2021 年国家心肺血液研究所睡眠研究一致 疾病研究计划“阐明健康和疾病背后的睡眠和昼夜节律机制” 以及“开发用于早期预测和检测睡眠不足和睡眠和睡眠的工具和/或方法 儿童和青少年的昼夜节律紊乱，以促进终身健康和福祉并预防疾病。”