Understanding the link between sociocultural and biological factors to brain health across race & ethnicity in midlife

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PROJECT SUMMARY/ABSTRACT Black and Latinx in the U.S. experience greater brain aging and increased risk for Alzheimer’s disease and related dementias (ADRD) than Whites. The weathering hypothesis, originally proposed to explain the premature decline of health experienced by Black women exposed to stress, social disadvantage, structural racism, and discrimination, may help explain the faster brain aging and racial/ethnic disparities in ADRD in late life among older Black and Latinx people. Identifying potential targets for interventions to reduce disparities in brain health in the diverse aging population is of critical importance to the rapidly expanding aging population. Biological aging, the progressive loss of system integrity that occurs as we age is proposed as a modifiable process mediating this health inequality. Further, previous studies show that ADRD pathology begins as early as midlife, thus, it is critical to evaluate these relationships in midlife, a time that may be the most critical period for intervention. This proposal leverages data collected from the Offspring Study of Mechanisms for Racial Disparities in ADRD—a longitudinal study of racially/ethnically diverse middle-aged adults with MRI, blood assays, and interview data. The primary goals of this K99/R00 proposal are to determine the relationship between advanced biological aging and MRI biomarkers in racially/ethnically diverse middle-aged adults and to characterize the links between lifecourse socioeconomic status (SES), advanced biological aging, and MRI biomarkers of aging and ADRD. This K99/R00 proposal lays the foundation for an independent research career focused on understanding the causal pathways linking environmental, sociocultural, and biological factors to disparities in brain health across race/ethnicity. Together, the research and training plans will allow the applicant to (1) develop expertise in using multiple modalities to understand biological and brain aging; 2) master causal inference modeling, with special emphasis on multigroup analyses that compare relationships by race/ethnicity; 3) broaden knowledge base of health-defining sociocultural factors in midlife; and 4) establish a strong foundation in theory and research related to cultural influences on brain health. These experiences will supplement the applicant’s strong existing background in cognitive neuroscience and cognitive aging. Results from this study may point to new sources of racial/ethnic disparities in brain aging and ADRD that could be future targets for intervention, and help to validate accessible, blood-based targets for monitoring or prevention of ADRD among diverse communities of middle- aged adults.