The objective of the proposed career development plan is to launch the candidate's independent research career investigating the mechanisms by which racial disparities in exposure to early life social disadvantage (ELSD) promote accelerated subclinical and clinical brain pathology in African Americans (AA) across the life course. There are pronounced AA-White disparities in brain health endpoints including stroke, dementia, and cognitive decline. Recent data suggest that earlier disparities in brain health are also noted on magnetic resonance imaging (MRI). Exposure to greater ELSD - characterized by harsher residential and neighborhood environments and lower parental socioeconomic status (SES) - may chart a course towards an accelerated onset of and more severe brain pathology observed in AAs as characterized by multiple MRI-assessed indicators of subclinical brain pathology including lower gray matter (GM) volumes, greater white matter lesion volumes and lesser WM integrity. This application was originally submitted in response to the NIA K01 PAR- 09-136, "Promoting Careers in Aging and Health Disparities Research" that sought to delineate social factors that precipitate late life health disparities among minorities and elders from disadvantaged backgrounds. Due to discontinuation of that PAR, the current application is a resubmission to the NIA K01 PA-11-190, Mentored Research Scientist Development Award. This K01 will allow the candidate to extend her prior training on the relation of psychosocial factors to coronary heart disease risk among adolescent and early to midlife AAs by providing training in (1) the life course perspective and accelerated theories of aging, particularly as applied to racial disparities in social disadvantage and health, and (2) the brain and related vasculature, and MRI- indicators of brain pathology including subclinical cerebrovascular disease. The proposed project will be a substudy to the ongoing HANDLS SCAN project - itself an ancillary study to the Healthy Aging in Neighborhoods of Diversity Across the Life Span (HANDLS) study, a 20-year epidemiological investigation conducted by the NIA Intramural Research Program that assesses health disparities in >3,500 AA and White adults (ages 30-64 at baseline) living in Baltimore, MD. In up to 400 HANDLS participants, HANDLS SCAN examines the relations of race and adult SES to MRI-indicators of brain pathology that may underlie risk for stroke, dementia, and cognitive and functional decline. In the proposed study, 300 HANDLS SCAN participants will complete measures of ELSD to determine: (1) whether ELSD is related to MRI-indicators of brain pathology predictive of future stroke, cognitive, and functional decline, and whether these associations are more pronounced in AAs than in White adults, and (2) explore potential psychosocial, behavioral, and biomedical mediators of these associations. The interdisciplinary training outlined in this application will allow the candidate o carve out a unique and unmatched research program that is desperately warranted by the pronounced prevalence of cerebrovascular and other brain disease in AAs. The interrelations among life course social disadvantage, accelerated aging, and brain health endpoints have been grossly understudied and are crucial to developing appropriate prevention and intervention strategies geared toward reducing and ultimately eliminating race-related health disparities in brain aging.
Pronounced racial disparities are observed across multiple clinical and subclinical brain health endpoints in African Americans compared to Whites and may be attributable, in part, to accelerated age-related disease processes. Great public health relevance lies in our ability to understand the relation of racial disparities in early life social disadvantage to subclinical markers of brain pathology predictive of future clinical endpoints such as stroke, dementia, and cognitive and physical decline in African Americans, and related multi-level mediators of this relation. Such research can facilitate development of appropriate strategies in prevention and intervention critical to the reduction and ultimate elimination of health disparities in multiple brain health endpoints.