PROJECT SUMMARY/ABSTRACT Aging persons living with HIV (PLHIV) are now at risk of age-related neurodegenerative diseases such as Alzheimer’s disease (AD) and its precursor amnestic mild cognitive impairment (aMCI). Due to the potential for compounding effects of HIV and aging on the brain, as well as high rates of medical conditions (e.g., chronic inflammation) that are risk factors for AD, PLHIV are likely at higher risk for neurodegenerative diseases such as AD. Identifying PLHIV with aMCI is complicated because the defining characteristic of aMCI, memory dysfunction, is also common in HIV-associated neurocognitive disorders (HAND), which are still prevalent in the cART era (30-50%), particularly among older PLHIV. In order to provide early, targeted interventions and predict cognitive impairment progression, it is imperative that clinicians are able to accurately differentiate HAND and aMCI. However, because this aging trend is relatively recent, there is a paucity of research aimed at disentangling HAND and aMCI. Due to differences in underlying brain changes, memory dysfunction presents differently on neurocognitive testing in HAND versus aMCI. Specifically, HAND (more prefrontally- and subcortically-based) is characterized by impairment in recall but relatively preserved recognition performance on neurocognitive tests, whereas aMCI (associated with medial temporal lobe atrophy) is characterized by impairment in both recall and recognition. Therefore, recognition may be a clinically-useful neurocognitive marker to differentiate HAND and aMCI. To-date, the majority of HIV neurocognitive studies have preferentially focused on recall deficits and have not examined recognition. Research is needed to assess the clinical utility of recognition in disentangling aMCI and HAND by examining if recognition correlates with neuroanatomical structures associated with aMCI. This F31 research project therefore aims to 1) examine neuroanatomical correlates of recall and recognition, and 2) examine if structural integrity of the medial temporal lobe is associated with future amnestic decline (i.e., decline in recall and recognition performance) among older PLHIV. Additionally, exploratory analyses will probe biological mechanisms that put PLHIV at greater risk of aMCI by examining the role of peripheral inflammation in memory impairment and brain integrity. This project will utilize longitudinal, archival neuroimaging and neuropsychological data collected from the CNS HIV Antiretroviral Therapy Effects Research (CHARTER) program. Finally, the training opportunities afforded by the F31 funding mechanism will facilitate the applicant’s long-term goal of becoming an independent academic neuropsychologist dedicated to improving detection of age-related neurocognitive decline in clinically-diverse, at-risk populations.