Project 2: Aging Healthy Together: Precision Profiles of Resilience and Risk

SUMMARY/ABSTRACT: Project 2 Aging Healthy Together: Profiles of Resilience and Risk Project 2 will obtain biomarkers related to four areas of risk for age-related cognitive impairment (ARCI) and cognitive decline, including Cardiovascular Insufficiency, Glucose Dysregulation, Inflammatory Profile, and Immune Dysfunction. We will determine whether profiles of risk and resilience in these four areas predict cognitive functioning among older adults and identify optimal predictive models for three race-ethnic groups – Hispanic/Latino, non-Hispanic Black, and non-Hispanic White. We will also determine whether the influence of these predictors on age-related cognition is mediated by functional and structural MRI measures, including diffusion MRI, resting state connectivity, perfusion, and hippocampal volume. In-depth assessments will be obtained from 1,620 participants, ages 50 to 79, at four clinical sites – Tucson (University of Arizona), Atlanta (Emory University), Miami (University of Miami), and Baltimore (Johns Hopkins University) – including demographics and lifestyle factors, psychosocial measures, biometric measures, blood biomarkers, MRI, carotid ultrasound, and genomics. Biomarkers and genetic risks will be used to predict individual differences in cognitive functioning (cross-sectionally) in three domains – memory, executive functions, and processing speed. Preliminary evidence for the impact of risk factors on longitudinal cognitive change will also be obtained. The proposed project is a critical step in achieving the ultimate goal of the Precision Aging Network (PAN) to develop a novel precision medicine diagnostic and prognostic system that will match an individual’s risk profile with a customized therapeutic and healthy lifestyle plan to maintain cognitive health across the lifespan. This goal requires understanding how categories of risk and their specific risk factors relate to cognitive functioning in order to identify novel targets for intervention and create therapeutic approaches for ARCI and cognitive decline. Matching cognitive healthspan with human lifespan will improve productivity and quality of life, extend independent living, and decrease the risk for Alzheimer’s disease (AD) and AD-related dementias (ADRD). PHS 398/2590 (Rev. 06/09) Page Continuation Format Page