Innovative Deep Phenotyping of African Americans at Risk for Alzheimers disease

PROJECT SUMMARY A critical gap in Alzheimer’s disease (AD) and Alzheimer’s disease related disorders (ADRD) clinical research is the vast under-under-representation of Black/African American (AA) older adults. It is well-documented that AD+ADRD is more prevalent in AA individuals relative to white individuals of European ancestry. Early detection of AD+ADRD is critical for clinical trials aiming to develop optimal therapeutics. Without adequate representation of AA in cognitive and biomarker studies examining the earliest changes in AD+ADRD, the diagnostic, prognostic, and clinical utility of promising biomarkers and their effects on cognition cannot be established. Therefore, there is a pressing need to include and deeply phenotype AAs using novel cognitive and biomarker assessments that consider the multiple co-morbidities identified in this population. Study location has been identified as one of the most prevalent enrollment barriers for AA older adults. This current research proposal leverages our vast expertise in conducting home-based assessment to evaluate clinical and neuropsychological status with equipment that we place within the home. Importantly, we will provide door-to-door transportation for MRI and amyloid PET imaging studies that we have successfully employed to recruit and retain culturally diverse older adults including AA, with and without cognitive impairment into biomarker studies. This will facilitate a user-friendly and effective approach that supports the engagement of AA older adults. Other important and innovative aspects of our proposed study include: a) the use of our novel Cognitive Challenge Tests (CCTs) that employ sensitive and specific cognitive assessment paradigms that have been associated to biomarkers of AD and neurodegeneration, and have been validated for use in AA older adults with and without Mild Cognitive Impairment (MCI); b) use of state-of-the-science plasma-based markers of AD and neurodegeneration that leverage extremely sensitive SiMoA technology; c) we will uniquely relate our novel CCTs at baseline and longitudinally to changes over time in serially collected plasma biomarkers (e.g., p-tau181, p-tau217, NfL, GFAP), d) comparison of plasma markers of AD and neurodegeneration with amyloid PET imaging and extra-cellular free water diffusion as well as neurodegenerative changes on MRI; e) accounting for the comorbidity of common chronic conditions in the AA population, we will obtain sensitive measures of cerebrovascular disease, inflammation, diabetes and metabolic risk, as well as chronic kidney disease; f) structural and social determinants of health will also be assessed. The deep phenotyping of 270 non-Hispanic AA older adults in the proposed research study and our resource sharing plan will accelerate efforts to gain critically needed knowledge of AD+ADRD in a seriously underrepresented AA group. The data obtained will promote the reproducibility of this work in extant databases that include AA and can facilitate comparison of findings with non-AA samples. This important cohort will continue to be followed throughout the funding period and beyond.