Administrative supplement of gas-free cerebrovascular reactivity (CVR) MRI in vascular cognitive impairment

项目摘要/摘要 这是对家长拨款执行额外工作的补充请求R01NS115771，以回应 不是-AG-23-008。有效的抗逆转录病毒药物抑制病毒导致了接近正常的生活 艾滋病毒携带者的预期(威尔斯亲王医院)。然而，由于PHH的寿命更长，超过一半(52.7%) 2020年)在美国50岁或以上。尽管病毒抑制和免疫重建，PWHs面临 与普通人群相比，中风和神经认知障碍的发生率增加。这个 艾滋病毒相关神经认知障碍(HAND)的患病率估计占所有艾滋病毒阳性患者的30%-50% 年龄较大的威尔斯亲王的患病率较高。脑血管功能障碍与 PWH中脑血管疾病的发生率增加，这可能是导致HAND的关键因素。然而， 脑血管功能障碍作为手部致病因素的直接证据仍然缺乏。 家长奖(R01NS115771)专注于开发一种用于标测的新MRI技术 脑血管反应性(CVR)及其作为血管认知障碍(VCI)早期生物标志物的应用。 CVR是脑血管对刺激的反应能力的指标，是对大脑的 血管功能。先前的研究表明，VCI患者的CVR降低。尽管这些都有很好的记录 结果，CVR在临床实践中通常不被测量，主要是由于在应用 血管成像过程中的“挑战”。目前的CVR测量通常需要血管方面的挑战 在成像期间，包括注射药剂(例如，乙酰唑胺)或吸入 二氧化碳气体。然而，这些技术复杂且成本高昂，需要特殊的设备，而且有可能 诱导血管挑战的生理操作的副作用。因此，无级变速器的研制 不需要明确的血管挑战的技术将扩大CVR的临床用途，使其成为一种 为研究PWH的脑血管功能障碍提供了一种可行的工具，并有可能成为手部的生物标志物。 在这个补充中，我们提出了一个补充项目，使用了家长中提出的新技术 测量PHH患者CVR和认知功能的方案。我们的目标是：1)比较三组患者的CVR 参与者(50-85岁)：20名手部PWHs，20名无手PWHs，10名HIV血清阴性者 (SN)对照(母项目也研究60-85岁的健康对照)；2)确定CVR是否可以 在FLAIR核磁共振上预测手部状态、认知分数和WMH。我们假设1)这三个国家 参与者组，有手的PWH的CVR最低，不带手的PWH的CVR低于正常 2)CVR测量将预测认知障碍的严重程度和 脑血管结果。这项初步研究将提供初步数据和分析所需的更大的 通过未来的R01应用程序进行全面研究。

Project Summary/Abstract This is a supplemental request to perform additional work on parent grant R01NS115771, in response to NOT-AG-23-008. Effective antiretroviral medications for viral suppression have led to near-normal life expectancies in persons with HIV (PWH). However, since PWHs are living longer, more than half (52.7% in 2020) are 50 years of age or older in the U.S. Despite viral suppression and immune reconstitution, PWHs face increased rates of stroke and neurocognitive impairment compared with the general population. The prevalence of HIV-associated neurocognitive disorders (HAND) was estimated to be 30-50% of all HIV-positive individuals, with higher prevalence in the older PWH. Cerebrovascular dysfunction has been linked to the increased incidence of cerebrovascular diseases in PWH, which may be a key contributor to HAND. However, direct evidence of cerebrovascular dysfunction as a contributory etiology for HAND is still lacking. The parent award (R01NS115771) focuses on the development of a novel MRI technique for the mapping of cerebrovascular reactivity (CVR) and its utility as an early biomarker of vascular cognitive impairment (VCI). CVR, an index of cerebral vessel’s capacity to dilate in response to stimulation, is a measure of the brain’s vascular function. Previous studies demonstrated reduced CVR in VCI. Despite these well-documented findings, CVR is not commonly measured in clinical practice, primarily due to logistical difficulties in applying a vascular “challenge” during imaging. The current CVR measurements typically require a vascular challenge during imaging, involving either the injection of a pharmacological agent (e.g., acetazolamide) or the inhalation of CO2 gas. However, these techniques are complex and costly, requiring special equipment, and possible side-effects of physiological maneuver to induce the vascular challenge. Therefore, development of a CVR technique that does not need an explicit vascular challenge will broaden the clinical utility of CVR, making it a feasible tool to study cerebrovascular dysfunction in PWH, and possibly become a biomarker for HAND. In this supplement, we propose a supplement project, using the novel technique proposed in the parent protocol to measure CVR and cognitive function in PWHs. We aim to: 1) compare the CVR in three groups of participants (50-85 years of age): 20 PWHs with HAND, 20 PWHs without HAND, and 10 HIV-seronegative (SN) controls (the parent project also studies healthy controls 60-85 years); 2) determine whether CVR can predict HAND status, cognitive scores, and WMH on FLAIR MRI. We hypothesize that 1) across the three participant groups, PWH with HAND will show the lowest CVR, with lower than normal CVR in PWH without HAND, compared to SN controls; 2) the CVR measures will predict the severity of cognitive deficits and cerebrovascular outcomes. This pilot study will provide preliminary data and analyses needed for a larger more comprehensive study through a future R01 application.