The Impact of Social, Genetic and Neuroimaging Factors on Cognitive Functioning in the Black Community

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PROJECT SUMMARY The applicant seeks this K01 award to gain expertise on integrating social factors and neuropsychological assessments to examine within race heterogeneity for cognitive decline risk factors in the Black community. To achieve these goals, the applicant plans to leverage her strength is quantitative methodology for biomarker data to gain expertise in four critical areas of training: (1) research neuropsychological testing and community engagement; (2) health disparities and lifecourse factors; (3) genetics; and (4) professional training. With the guidance from her expert mentorship team and through a detailed training plan, the applicant will develop an in-depth knowledge in these training areas and enable the applicant to be well positioned to successfully complete the proposed aims of the K01. The overall research goal of this K01 application is to determine how social, neuroimaging markers, and genetic risk factors contribute to cognitive decline in non-demented older Black individuals. Research suggests current “well-established” risk factors for cognitive decline and Alzheimer’s disease (AD), which have been identified primarily in the white community, do not behave the same in Black individuals. Thus, it is critical to explore potential heterogeneity in risk factors within the Black community in order to accurately predict risk for cognitive decline. The first part of aim 1 examines the effect of early and current social factors on neuroimaging measures that have previously been associated with cognition (e.g. structural magnetic resonance imaging measures and vascular burden measured as white matter hyperintensities) in self-identified non-Hispanic Black participants. The second part of aim 1 will determine if these neuroimaging markers mediate the association of social factors and cognitive decline. We hypothesize that more social disadvantage will be inversely associated with AD-specific brain regions and faster rates of cognitive decline. We also hypothesize that neuroimaging measures will partially mediate the association of social factors on cognitive decline. Differences in racial groups may be due to social factors, which members of the Black community are disproportionately impacted. Finally, it is important to remember that race is a social construct and is dependent on self-identification, with no biological root. Moreover, recent studies suggest that genetic ancestry may influence risk for AD and impact pathological features of aging. It is unclear if genetic ancestry and social factors correlate, or if they have unique contributions to cognitive decline. Thus, our final aim will determine if genetic ancestry and/or social factors differentially influence the effect of APOE4 on cognitive decline. The primary hypothesis is that Black participants with more social disadvantage throughout life, will inversely effect these risk factors and have a faster rate of cognitive decline. We will also investigate if this association impacts conversion from mild cognitive impairment to AD dementia. Completion of these aims, along with the training from an experienced multidisciplinary mentoring team, will generate data and support for a future R01 application collecting data from members of the Black community in Los Angeles County.