PROJECT ABSTRACT Despite an aging population with high prevalence of risk factors for cognitive impairment, scalable, accessible, and accurate tools to detect cognitive impairment and Alzheimer’s disease (AD) in sub-Saharan Africa (SSA) are lacking. Recently developed plasma biomarkers (phosphorylated tau, P-Tau181; neurofilament light chain, NfL; glial fibrillary acidic protein, GFAP) and a brief digital cognitive assessment (Brain Health Assessment, BHA) are promising tools to expand access to AD diagnostic screening in SSA. However, these tools have not previously been evaluated in SSA populations. Additionally, the influence of HIV infection and the performance of these tools to detect cognitive impairment and AD in people living with HIV (PLWH) are unknown. The overarching goal of this administrative supplement is to validate the use of these novel plasma biomarkers and an adapted BHA as screening tools to detect cognitive impairment, a defining feature of AD, in a rural Ugandan population with a high burden of HIV infection. The central hypothesis is that plasma biomarkers and the BHA will detect and classify cognitive impairment in a rural SSA cohort with high validity in both PLWH and HIV-uninfected (HIV-) individuals, and that they will be promising tools for non-specialists to advance AD diagnosis in this setting. The project fits squarely within the goals of the parent study (R01 AG059504), a prospective cohort study of older-aged (>48 years-old) adults in rural Uganda including 300 PLWH on chronic antiretroviral therapy and 300 HIV- individuals that aims to determine the trajectory of aging-related morbidity and quality of life in this population. In specific aim 1 we will add measurement of plasma biomarkers (P- Tau181, NfL, GFAP), and assess their performance in discriminating cognitive impairment, defined by reference-standard neuropsychological testing, in the total cohort and in PLWH compared to HIV- individuals. In specific aim 2 we will first translate and adapt the BHA using mixed methods. To accomplish this, the BHA will be adapted using bilingual experts, local focus groups, and participant interviews, and then tested for feasibility. After adaptation, the BHA will be administered to study participants, concurrent and discriminant validity will be estimated, and performance will be determined in detecting cognitive impairment compared to reference-standard neuropsychological testing in rural Uganda. The proposal is responsive to the Notice of Special Interest by expanding the parent study to include a focus on AD detection tools, and it fits within the scope of the parent study by including AD-relevant measures as determinants of aging-related morbidity and quality of life in this population. Successful completion of this proposal is relevant to AD by expanding the reach and generalizability of promising AD diagnostic screening tools to high-risk and low-resource populations in SSA and in PLWH. Data from this project will fo...