Clinical spectrum and societal impact of cognitive impairment, alzheimer's and related dementias among people with HIV in uganda - as people living with HIV (PWH) reach older age, determining their…

The National Institute on Aging awarded Massachusetts General Hospital $1,732,063 on February 15, 2026, under the Aging Research program (CFDA 93.866) to conduct a longitudinal study measuring the prevalence, classification, and pathophysiologic contributors to mild cognitive impairment and Alzheimer's disease and related dementias among older people living with HIV in Uganda, with comparison to demographically similar HIV-uninfected controls.

The research involves comprehensive neuropsychological assessments conducted annually over four years in a cohort of 600 older adults (approximately 300 with HIV and 300 without HIV), deep phenotyping with novel plasma biomarkers and neuroimaging, identification of cognitive impairment using multidisciplinary case consensus criteria, and machine learning techniques to analyze structural brain changes. Preliminary data from 300 virologically suppressed people with HIV (mean age over 60) and 300 controls in Uganda demonstrated that more than 30 percent of people with HIV exhibit characteristics of mild cognitive impairment, and that brain MRI and machine learning add critical phenotyping data to standard neuropsychological batteries.

Work is performed in Boston, Massachusetts, with period of performance from February 15, 2026, through January 31, 2031. The National Institute on Aging supports biomedical and behavioral research and training in aging, with emphasis on preventing and treating Alzheimer's disease and related dementias.

Massachusetts General Hospital passed funding to two sub-recipients: Mbarara University of Science and Technology Faculty of Medicine (sub-award issued May 11, 2026) and Kabwohe Clinical Research Center (sub-award issued July 30, 2026). Both organizations, operating in southwestern Uganda, manage local participant recruitment, informed consent, neuropsychological and clinical assessments, brain imaging, biospecimen collection and shipment, data entry and quality assurance, and staff supervision at study sites including the Immune Suppression Syndrome Clinic at Mbarara Regional Referral Hospital and the Kabwohe HIV Clinic.

Clinical spectrum and societal impact of cognitive impairment, alzheimer's and related dementias among people with HIV in uganda - as people living with HIV (PWH) reach older age, determining their risk for mild cognitive impairment (MCI) and alzheimer's disease and related dementias (adrds) is emerging as a major public health priority. Because HIV is relatively rare in the united states, particularly in the elderly, data in this area have largely been limited to young populations and lacked large samples with brain imaging and biomarkers to determine disease phenotypes. Moreover, social and clinical health predictors of MCI/adrd differ meaningfully in PWH, so risk factors and their impact on households cannot be extrapolated from other populations. To respond to these gaps, we will leverage a team of experts in HIV epidemiology, diagnosis and phenotyping of MCI/adrds with fluid and imaging biomarkers, and machine learning (ML), and a large and well-established cohort of older people with HIV. Preliminary data generated by our team include neuropsychological screening of 300 older virologic suppressed PWH in uganda (mean age >60), and 300 demographically similar people without HIV, showing that >30% of PWH have characteristics of MCI and that brain MRI and ML techniques add critical phenotyping data to standard batteries. Four specific aims are proposed: aim 1: determine the prevalence and classification of MCI/adrds (1A) and compare trajectories of cognitive performance (1B) between older PWH and similar people without HIV. Comprehensive neuropsychological assessments will be completed in older adults with and without HIV in the cohort (n=600) annually during years 1-4. MCI/adrds will be identified using multi-disciplinary case consensus criteria to provide diagnoses and underlying etiologies. Aim 2: identify pathophysiologic contributors to MCI/adrds in older adults through deep phenotyping with novel plasma biomarkers and neuroimaging. Assessments will include AΒ42/AΒ40, p-TAU217, gfap, and NFL biomarkers and brain mris to characterize phenotypes. Aim 3: estimate the psychosocial and economic impacts of MCI/adrds on adult household members. We will conduct in-depth interviews (n~40, aim 3A) to learn about lived experiences of caregivers, and quantitative surveys (aim 3B) to all adult household members of the cohort (n~1800) on employment and resource use, caregiving burden, quality of life, stigma, social participation, loneliness, and mental health. We will compare participants by the presence VS absence of MCI/adrds in the household. Aim 4: discover and validate novel, multilevel mechanistic models of MCI/adrds among older PWH by employing ML methods with the full array of data collected in aims 1-3. We will determine which combinations of highly dimensional features reliably classify individuals according to MCI/adrds profiles. Completing these aims will advance our understanding of MCI/adrds epidemiology among older PWH. In doing so, IT will lay the foundation for diagnostic and intervention efforts to address research priorities for PWH in the united states and beyond.