Predictors of Altered CNS Structure, Function, and Connectomics in the Elderly using a Health Disparities Framework

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Abstract The goal of this project is to leverage the diverse sample in our Human Connectome Project (HCP) Study, Connectomics in Brain Aging (COBRA) , to investigate the role(s) of structural and social determinants of health in the natural history of Alzheimer’s Disease (AD) utilizing a health equity framework. We propose that racial inequities in the development of cognitive impairments in the context of AD are driven by pervasive structural and institutionalized inequities that shape risk and disadvantage at multiple levels, including biological, environmental, behavioral, sociocultural, as proposed in the NIA Health Disparities Research Framework. Our organizing principle is that the expression of cognitive dysfunction in the elderly is the result of two independent processes affecting the connectome — the first is the neuropathology associated with AD. The second process historically has been referred to as “modifiable individual risk factors”, however, this fails to recognize that individual risk is influenced by factors that are outside of an individual’s control, and which will be measured using a health equity framework. We will augment our existing sample (50% Black, 65% Female) with an additional 150 participant (total sample ~400 with up to four study visits). Each of the participants will contribute the HCP-specified demographic, behavioral and laboratory data. All of the participants will undergo extensive brain imaging biannually including MRI and PET (amyloid and tau tracers). All of the MRI data will be uploaded to the Connectome Coordinating Facility, and the behavioral/cognitive, PET data will be uploaded to the NIMH Data Archive. Locally, we will use these data to address specific questions related to structure, function, AD, aging and vascular disease in multi-modality studies leveraging the differential advantages of MRI, fMRI, and in vivo Aβ and tau imaging.