HIV remains a major public health problem, particularly for the Latina/o population. US-dwelling Latinas/os are at increased risk for HIV-infection compared to non-Hispanic whites and suffer a disproportionate burden of HIV-associated neurocognitive disorder (HAND) which may be amplified with age. HIV-infected (HIV+) Latinas/os of Puerto Rican origin have the highest prevalence of HAND (~78%) of any group in the US (HIV+ Mexican Americans: 44%; African Americans: ~40%, & non-Hispanic whites: ~40%). Older HIV+ Latinas/os (50± years) appear to be at even greater risk for HAND and cognitive decline than their non-Hispanic white counterparts, and the pattern of cognitive impairment in HAND appears to differ by ethnicity. In the general HIV population, HAND is characterized by impairments in processing speed, attention, and executive functioning consistent with involvement of the frontostriatal circuitry. HIV+ Puerto Rican Latinas/os present an atypical amnestic memory profile more consistent with medial temporal lobe (MTL) involvement. Despite these important disparities, differing cognitive profiles and possible differences in affected neural structures, the literature on HAND in Latinas/os is almost entirely cross-sectional, does not include HIV-uninfected (HIV-) controls, lacks studies focused on brain integrity in this population, and has yet to examine the mechanisms underlying these disparities. Utilizing a culturally-tailored approach, the goals of this study are to investigate whether older HIV+ Latinas/os of Puerto Rican origin demonstrate worse patterns of decline in cognitive function and brain integrity compared to other ethnic/HIV status groups, and to uncover the biological (e.g., neuroinflammatory biomarkers [sTREM2, sCD14, sTNFR-II, & IL-6], cardiovascular burden) and sociocultural (e.g., acculturation, social adversity, stress) mechanisms conferring risk for neurodegenerative and cognitive changes in this population. To that end, this multidisciplinary study will deploy a longitudinal observational design with 90 HIV+ and 90 HIV-matched control adults (both groups will include: 70% Latina/o and 30% non- Hispanic white; aged 60-80 yrs) over 36-months. All participants will complete laboratory, neuromedical, multimodal neuroimaging, and comprehensive cognitive and sociocultural assessments. Longitudinal structural equation models will test relationships between ethnicity, HIV, and biological and sociocultural factors on cognition (global, learning, memory, & processing speed) and MRI brain indices (white matter lesion & MTL gray matter volumes; MTL intrinsic activity, & hippocampal intra-network connectivity). Addressing disparities in cognitive and brain health outcomes in Latinas/os offers a vital opportunity to elucidate HAND neuropathogenesis, disentangle the biological and sociocultural aspects of cognitive aging through the lens of HIV-infection, and identify modifiable factors to mitigate risk for cognitive decline. As this popu...