HABS-HD - Project 3

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HABS-HD PROJECT 3 ABSTRACT African Americans (AAs) currently suffer the highest burden of Alzheimer’s disease (AD) and Alzheimer’s Disease-Related Dementias (ADRD) while Hispanics (65% of which are Mexican American [MA]) will experience the greatest increase in disease burden by 2060. Additionally, emerging data supports racial/ethnic differences in the fundamental pathological biomarkers of Amyloid (A), Tau (T), and Neurodegeneration (N) in AD, as defined by the 2018 AT(N) framework (Project 1). Research also demonstrates a significant impact of vascular, metabolic and inflammatory (VMI) factors on AD outcomes, which are experienced at higher rates among AAs and MAs and, therefore, may impact AT(N) biomarkers (Project 2). Given that AAs and MAs experience a disparate burden of exposome and sociocultural factors previously linked to AD outcomes, these factors may contribute to observed AD health disparities and biomarker differences. In fact, the Link & Phelan “Fundamental Causes Theory” proposes that social factors may be ‘fundamental causes’ of disease and must be considered for successful intervention strategies. Milestones 1.B and 1.I of the NIA AD + ADRD Implementation Milestones explicitly call for examinations of the impact of exposome and social factors on AD/ADRD disparities. Therefore, Project 3 will evaluate the impact of exposome (i.e., neighborhood disadvantage) and sociocultural (i.e., acculturation, stress, perceived racism) factors on the prevalence, sequence and trajectories of cognitive decline as well as AT(N) defined biomarkers among the three largest racial/ethnic groups in the U.S. Therefore, Project 3 will address the following Specific Aims in alignment with the NIA Health Disparities Research Framework. Aim 1: Examine the link between neighborhood disadvantage and sociocultural factors on the presence and longitudinal progression of cognitive loss among African Americans, Mexican Americans and non-Hispanic whites. Aim 2: Examine the impact of neighborhood disadvantage and sociocultural factors on the presence, sequence and trajectories of AT(N) defined biomarkers among African Americans, Mexican Americans and non-Hispanic whites. Aim 3: Examine the impact of epigenetic factors on the link between neighborhood disadvantage and sociocultural factors on AT(N) defined biomarkers, and cognitive trajectories, among African Americans, Mexican Americans and non- Hispanic whites. Aim 4 (Project – Project Interactions): Collaborate with Projects 1 and 2 to develop a comprehensive understanding of AT(N) defined biomarkers across diverse populations. Aim 5: Utilize data from Project 3 as a comparison for other studies examining the impact of neighborhood disadvantage (e.g., Neighborhood Study), and sociocultural factors (e.g., WHICAP, SOL/INCA), on AD biomarkers and cognitive trajectories.