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

项目总结/摘要 这是对母授权R 01 NS 115771执行其他工作的补充请求，以响应 NOT-AG-23-008.有效的抗逆转录病毒药物抑制病毒导致接近正常的生活 艾滋病毒感染者的预期寿命（PWH）。然而，由于PWH的寿命更长，超过一半（52.7%） 2020年）是50岁或以上的美国，尽管病毒抑制和免疫重建， 与一般人群相比，中风和神经认知障碍的发生率增加。的 据估计，HIV相关神经认知障碍（HAND）的患病率占所有HIV阳性患者的30- 50 个别人士，与较高的患病率在较旧的威尔斯亲王医院。脑血管功能障碍与 PWH中脑血管疾病的发病率增加，这可能是HAND的关键因素。然而，在这方面， 脑血管功能障碍作为HAND的一个贡献病因的直接证据仍然缺乏。 母公司奖（R 01 NS 115771）侧重于开发用于标测的新型MRI技术 脑血管反应性（CVR）及其作为血管性认知障碍（VCI）早期生物标志物的效用。 CVR是脑血管响应刺激而扩张的能力的指数，是脑功能的量度。 血管功能既往研究表明VCI患者CVR降低。尽管这些证据确凿的 研究结果，CVR在临床实践中通常不测量，主要是由于应用 在成像期间的血管“挑战”。目前的CVR测量通常需要血管挑战 在成像过程中，包括注射药剂（例如，乙酰唑胺）或吸入 二氧化碳气体。然而，这些技术是复杂且昂贵的，需要特殊设备，并且可能需要额外的设备。 诱发血管挑战的生理操作的副作用。因此，开发CVR 不需要明确血管挑战的技术将扩大CVR的临床应用，使其成为一种 研究PWH脑血管功能障碍的可行工具，并可能成为HAND的生物标志物。 在这个补充中，我们提出了一个补充项目，使用父母提出的新技术， 测量PWH中的CVR和认知功能的方案。我们的目的是：1）比较三组CVR， 受试者（50-85岁）：20例伴HAND的PWH，20例不伴HAND的PWH，10例HIV血清阴性 (SN)对照组（母项目还研究了60-85岁的健康对照组）; 2）确定CVR是否可以 预测HAND状态、认知评分和FLAIR MRI上的WMH。我们假设1）在三个 参与者组中，PWH伴HAND的CVR最低，PWH不伴HAND的CVR低于正常CVR HAND，与SN对照相比; 2）CVR测量将预测认知缺陷的严重程度， 脑血管结局。这项试点研究将为更大规模的研究提供所需的初步数据和分析。 通过未来的R 01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.