ABSTRACT This application is in response to NOT-AG-23-008, the Notice of Special Interest Administrative Supplements for HIV/AIDS and Aging Research as a supplement to our parent grant R01AA017347. The proposed work extends our current project by using a creative constellation of imaging protocols and analyses that have the potential of identifying physiological markers of cerebrovascular compromise in people aging with HIV that may be exacerbated by alcohol use disorder (AUD) or other hazardous drinking. Health outcomes of people with HIV (PWH) who drink alcohol may be complicated by multiple comorbidities associated with continued heavy alcohol use and a range of alcohol use affecting brain health, including cerebrovascular status, and leading to deficits in cognitive and motor functioning. Understanding how alcohol exacerbates geriatric syndromes like falls, frailty, and cognitive decline in PWH may lead to strategies to improve health outcomes. This supplement will focus on people with HIV (PWH) with and without AUD comorbidity. Accordingly, we will invite a subset of older (>60 years) participants from our ongoing, longitudinal HIV study (i.e., 20 PWH, 20 PWH+AUD, 20 healthy controls), who are matched on age and sex; all HIV participants will be on ART and virally suppressed. Using a suite of neuroimaging protocols and functional measures to assess cerebrovascular health in these groups, we propose two specific aims: Specific Aim 1: To use noninvasive neuroimaging methods to assess the activity of the glymphatic system in brain white matter and test its cognitive and motor performance correlates. Hypothesis: Low DTI-ALPS ratios together with large PVWMH volumes identified with FLAIR will indicate glymphatic deficiency and correlate with poorer cognitive and motor performance and higher indices of frailty, measured as poor grip strength, postural instability assessed with a test of ataxia, and falls in the past year. Specific Aim 2: To use PCASL to measure local and global cerebral perfusion in gray matter. Hypothesis: Regional cortical perfusion deficits will index cortical cerebrovascular deficiencies and correlate with performance variables. Modifying factors will include smoking and high blood pressure. Exploratory analyses are relevant to both aims and will investigate moderating factors of sex, alcohol consumption (recency and amount), smoking, blood pressure, HbA1c and lipid levels.