A multidisciplinary study of Alzheimer's disease risk factors in Blacks/African Americans living with HIV

PROJECT SUMMARY NOT-AG-21-033 calls for applications that aim to “increase enrollment of underrepresented populations, expand the use of existing cohorts, and create robust estimates of [Alzheimer’s disease and related dementias (ADRD)] in diverse populations.” As a direct response to the call, we propose a 5-year cross-sectional, longitudinal, and observational study to investigate the impact of Alzheimer’s disease (AD) risk genes (with a focus on APOE ε4) on brain function in a highly vulnerable population, HIV+ older Blacks/African Americans, who may be at a greater risk of developing Alzheimer’s disease and related dementias but have been particularly understudied in ADRD research. In the USA, Blacks/African Americans have the most severe burden of HIV, accounting for ~40% of individuals living with HIV. Approximately 40% of HIV+ African Americans are 55 years old or older. This rapidly aging demographic presents an increasingly significant and urgent challenge in public health: advanced age is a significant risk factor for: i) HIV associated neurocognitive disorders (HAND) – the most common cause of dementia in people with HIV (PWH); and ii) Alzheimer’s disease (AD) – the most common cause of dementia in HIV uninfected older adults. Therefore, older African Americans with HIV are facing an increasingly greater risk of double-hit (HAND and ADRD), especially since the prevalence of AD is greater in African Americans than non-Hispanic whites. Furthermore, the potential interaction between HAND and AD remains to be elucidated but could posit additional risks. Indeed, a recent study revealed that a history of severe immunosuppression might exacerbate the impacts of APOE ε4, suggesting that HIV+ Blacks/African American ε4 carriers with a history of severe HIV disease may be at a much greater risk of developing ADRD later in life. In this project, a total of 120 AAs with HIV (60-80 y.o., 60 with and 60 without ε4) and 80 demographically matched controls (40 with and 40 without ε4) will be enrolled. All participants will be invited back for a longitudinal study visit (approximately two years after they finish their first full study visit). We will use a combination of neuropsychological tests, multimodal MRI, plasma amyloid and tau, and clinical evaluations to examine the impacts of ε4, HIV disease, and the probable interaction between ε4 and HIV disease severity in older Blacks/African Americans (AAs). In addition, we will examine the potential impact of genetic variations surrounding APOE (secondary goal). This project is supported by an established multidisciplinary team, existing cohorts, and strong preliminary data. The success of this project will help to address an increasingly urgent challenge in public health, and the knowledge and techniques developed in this project may also help to understand the greater risk of ADRD in older Blacks/African Americans without HIV disease.