Project Summary Cardiovascular (CV) risk factors in midlife are recognized to influence later-life cognitive status. Results from clinical trials have suggested that modifying CV risk factors in older adults may be a promising avenue to lower risk of late life cognitive decline. Herein, we propose a supplement, within the scope of the parent grant 2RF1AG041200, entitled ‘Lifespan Cardiovascular Risk Exposures and Alzheimer-related brain health: Bogalusa Heart Study’ which aims to identify modifiable risk factors shared by these conditions in a race- and sex-specific fashion, and determine the critical time windows to prevent and delay the onset of Alzheimer’s Disease and related dementia syndromes (ADRD) and minimize disparities. The parent grant will collect information on cognitive performance among 600 and neuroimaging of sub-clinical brain injury 200 black and white men and women who participate in the Bogalusa Heart Study (BHS) in middle age. The candidate Dr. De Anda-Duran, will leverage the data collected by the parent grant, by applying advanced analytical methods that will distinguish life-course (childhood to midlife) trajectories of CV risk factors that impact brain function. This work will expand on traditional neuropsychological (NP) approaches to characterize midlife cognitive performance by identifying subclinical NP phenotypes that may be more susceptible to progression to ADRD. Mild cognitive impairment (MCI) is a pivotal stage often leading to progression to ADRD; however, accurate identification of this prodrome is challenging, and inconsistencies might contribute to the neuropathological heterogeneity seen in ADRD. Adequate and timely characterization of neurocognitive phenotypes that more likely progress to dementia, and/or resemble MCI, using data- driven approaches can be a potential pathway to address disease burden and optimize patient eligibility for clinical trials and risk reduction interventions. Data-driven approaches appear to be more precise in identifying and classifying individuals based on distinct NP phenotypes linked with less ambiguous neuropathology. To this end, we propose to evaluate the relationship between life-course exposure to CV risk factors and midlife NP phenotypes among black and white participants from a semi-rural, community-based cohort of middle-aged adults located in Bogalusa, Louisiana. This work has important clinical and public health implications. Early characterization of cognitive phenotypes may better identify groups prone to progress to cognitive impairment syndromes and high-risk groups who may be more responsive to clinical interventions, and benefit most from targeted prevention strategies. Moreover, the proposed supplement will provide the candidate, Dr. De Anda-Duran, with the necessary period of protected time to gain the skills required to become and independently funded researcher.