Mayo Advancing Research Equity in ADRD Study in Jacksonville(MAREAS-Jax)

PROJECT SUMMARY/ABSTRACT Hispanics/Latinos (HL) and African Americans (AA) represent a rapidly growing proportion of the United States population (18.7% HL, 12.4% AA - US 2020 Census) who remain critically underrepresented in research of Alzheimer disease (AD) and AD-related dementia (ADRD), despite a 1.5-2-fold higher prevalence of dementia (vs non-Hispanic-white Americans). Underrepresentation in AD/ADRD research exacerbates health disparities and challenges the development and implementation of efficacious and safe risk-reduction strategies for AD/ADRD in HL/AA. Genetics do not fully explain disparate AD/ADRD risk, highlighting a fundamental knowledge gap concerning how genomic factors interact with comorbidities and lifespan exposures to Structural/Social Determinants of Health (SDoH; the “exposome”) to inform AD/ADRD risk. There is a critical need to identify clinical, SDoH, and biological factors that contribute to disparate risk in HL/AA; establish the relationship between exposures underlying AD/ADRD outcomes; use this information to mitigate disparities in AD/ADRD burden through education and risk factor modification; and broadly disseminate this information to inform the development of effective biomarkers and therapies. The Mayo Advancing Research Equity in ADRD Study in Jacksonville (MAREAS-JAX; Spanish for tides) will address this need. Aim 1 will advance recruitment of HL/AA cohorts (UH2) by developing/deploying outreach, recruitment, and engagement best practices for HL/AA in Jacksonville, Florida, through a bilingual (English-Spanish) research team, supported by community ambassador teams (CAT) and an external advisory committee (EAC) including experts in SDoH and AD/ADRD research. Aim 2 will identify relevant measures of AD/ADRD burden (UH2►UH3). SDoH, cognitive, clinical, and blood-based biomarker measures associated with cerebrovascular, amyloid, and tau burden, will be collected through comprehensive/culturally appropriate annual assessments and integrated with multi-omics data, structural (MR) and molecular (amyloid and tau) PET neuroimaging obtained at study entry, and every 2 years thereafter to identify modifiable dementia risk factors, blood-based biomarkers, and molecular signatures of AD/ADRD burden. Data collection will be standardized with input from EAC members to optimize scalability and promote sample/data sharing. Aim 3 will provide meaningful individualized feedback (UH3) to participants through a Brain Health Report detailing actionable risk factors and recommendations to mitigate intraindividual AD/ADRD burden. Aim 4 will use multi-omics measures to identify molecular targets and signatures that interact with the exposome and associate with AD/ADRD burden in HL/AA (UH3) using a systems biology approach with validated analytic pipelines and prioritizing broad data sharing following NIH’s findability, accessibility, interoperability, and reusability guidelines. In this way, MAREAS-Jax will chart the currents that drive disproportionate participation in AD/ADRD research and disparate AD/ADRD burden and will inform the design and implementation of strategies to shift these tides in Northeast Florida and beyond.