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

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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.