Neurovascular Uncoupling and Cognitive Impairments of Long COVID in Aging

项目概要/摘要 COVID-19大流行对全球公共卫生、社会及经济造成毁灭性影响。 新出现的数据表明，很大一部分患者从冠状病毒急性期康复 疾病2019（COVID-19）正在遭受一系列感染后发病的持续症状，通常 被称为“长期COVID”，严重影响该等患者的日常功能及生活质量。而 老年人特别容易患上这种疾病，人们越来越关注神经系统和 COVID-19在衰老过程中的神经退行性后遗症。虽然越来越多的证据表明，COVID-19往往 通过微血管损伤和大脑缺氧引起神经系统症状，我们假设， 神经血管解偶联是认知障碍的主要神经生理机制， 长期COVID老化。而脑血流量（CBF）可以使用动脉自旋标记（ASL）来估计。 灌注MRI，基于BOLD（血氧水平依赖性）测量的功能性MRI（fMRI） 神经元活动间接。最近，我们开发了一种创新的多频带和多回波（MBME） BOLD/ASL MRI序列，可同时测量血流动力学反应功能， CBF检测潜在的神经血管解偶联。这项概念验证研究将调查老年患者 （n=40）在12个月以上时从轻度COVID-19中恢复，并在感染后出现持续的认知症状 COVID-19，与年龄、性别和教育程度匹配的健康对照（HC）参与者（n=40）进行比较。 使用先进的神经成像技术，我们将确定任务诱发的测量之间的关系， 神经血管解偶联模式和长期COVID老化的长期认知障碍（目的1）， 确定静息态动态神经血管解耦与脑网络功能的关系 长期COVID在衰老中的改变和持续性认知障碍（目标2），并评估相关性 内源性大麻素信号系统（ECS）的措施和神经血管解偶联模式和认知 长期COVID对衰老的损害（目标3）。本工作具有较高的科学性和

Project Summary/Abstract The COVID-19 pandemic is having a devastating impact on public health, societies, and economies worldwide. Emerging data indicate that a substantial proportion of patients recovered from the acute stages of Coronavirus disease 2019 (COVID-19) are suffering a constellation of persistent symptoms with onset after infection, often referred to as "Long COVID", which severely affect the daily function and quality of life of those patients. While aged individuals are particularly vulnerable to this disease, there is growing concern about neurological and neurodegenerative sequelae of COVID-19 in aging. While increasing evidence shows that COVID-19 often causes neurological symptoms via microvascular injuries and hypoxia in the brain, we hypothesize that neurovascular uncoupling is the primary neurophysiological mechanism underlying the cognitive impairments of Long COVID in aging. Whereas cerebral blood flow (CBF) can be estimated using the arterial spin labeling (ASL) perfusion MRI, the functional MRI (fMRI) based on the BOLD (Blood-oxygen-level-dependent) measures neuronal activity indirectly. Recently, we have developed an innovative multiband and multi-echo (MBME) BOLD/ASL MRI sequence that enables simultaneous measurement of hemodynamic response function and CBF to detect potential neurovascular uncoupling. This proof-of-concept study will investigate elderly patients (n=40) at 12+ months recovered from mild COVID-19 with persistent cognitive symptoms onset after contracting COVID-19, in comparison with age, gender and education matched health control (HC) participants (n=40). Using advanced neuroimaging, we will determine the relationships between measures of task-evoked neurovascular uncoupling patterns and long-lasting cognitive impairments of Long COVID in aging (Aim 1), determine the relationships of resting-state dynamic neurovascular uncoupling and brain network function alterations and persistent cognitive impairments of Long COVID in aging (Aim 2), and evaluate the associations of endocannabinoid signaling system (ECS) measures and neurovascular uncoupling patterns and cognitive impairments of Long COVID in aging (Aim 3). This work has high scientific and