Project 2: Cardiometabolic Disease in HAALSI—Abstract High-quality data is critical for guiding research and resource allocation in low- and middle-income countries (LMIC) to ensure a healthy aging population. Cardiometabolic diseases (CMDs) have become a leading cause of death in sub-Saharan Africa, an effect of rapid epidemiologic, social, and economic transitions. These transitions have been unusually intense in South Africa. This rise in CMD-related mortality is catastrophic to families and households, given the critical role older persons play in providing childcare, supporting schooling, and countering food insecurity as recipients of social grants. Yet reliable data on the rate of change in CMD and its risk factors in South Africa and sub-Saharan Africa remain scarce. In South Africa, CMD risk is further exacerbated by interactions with human immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS; 23% prevalence in the HAALSI cohort). Coupled with longer life expectancy, CMD may also contribute to cognitive impairment and dementia in African populations. Data on novel CMD risk factors are scarce, and the incidence of acute CMD events (e.g., myocardial infarction, stroke, heart failure exacerbations) is largely unknown in South Africa. It is critical to measure CMD prevalence and risk factors more precisely in order to assess their relationship to mild cognitive impairment (MCI) and dementia in aging populations. Project 2 sits within HAALSI which was launched in 2014 as a program project (P01) emphasizing cognitive and physical function, CMD, HIV, and the social, economic and health system conditions that produce wide health disparities in South Africa. HAALSI was built upon the strong infrastructure of the Health and Demographic Surveillance System (HDSS) in Agincourt, South Africa. We found that from 2014 to 2021, the prevalence of several CMDs in the rose significantly, with CMD now the leading cause of deathrural South Africa. Here we request a second renewal for five years (2023-2028). The goal of our renewal is to leverage the data from our prior waves and increase the deep phenotyping of our HAALSI Agincourt cohort to reveal major pathways linking risk factors to CMDs, and subsequently to MCI and dementia, in under- resourced South African populations; as well as to develop a baseline of CMD at the national level with an additional sample of 4500 new men and women (and their partners) over 40 years of age. We have 3 aims in Project 2. AIM 1: Elucidate the trajectory and scope of CMD and novel CMD risk factors in the HAALSI cohort in rural Agincourt and nationally. AIM 2: Examine the relationship between vascular risk factors and cognitive function, MCI, and dementia in an HIV endemic aging population. AIM 3: Evaluate the potential impact of recent health and social policies implemented to reduce CMD on cognitive decline, MCI, and dementia. HAALSI enables progress in understanding and reducing CMD burden and related path...