Aging Research Characterizing Health Exposome via Social factors (ARCHES)

Our long-term goal is to employ an innovative stakeholder‑informed research design to establish a project advisory committee, to collaborate with our partners to recruit, enroll, and retain a cohort of African Americans (AA) participants and, then, to examine causal mechanisms that increase the risk of Alzheimer disease (AD) within the cohort. The long preclinical stage of AD, as reflected in biomarkers among adults, is a key risk factor for symptomatic AD. However, despite AA having a higher risk of developing AD, recent studies suggest that they have less abnormal levels of biomarkers than the general population in cognitively normal samples. This study aims to examine other risk factors of cognitive decline and AD, such as depression, stress, and social and environmental factors (referred to as the exposome), in a population‑based cohort of AA participants.
This research is significant because there are nearly 46 million AA, comprising 13% of the population in the United States. The AA older adult population is expected to increase, from 4.4 million older adults in 2016 to 12.1 million by 2060. As the population is projected to grow, AD research is limited to participants from homogeneous groups. This narrow focus limits insight into how exposome mechanisms influence disease risk across the general population. Closing this evidence gap is crucial, as epidemiological data indicate that some groups experience a 1.5- 2x increased likelihood of AD incidence compared to the general population. Our Aims will (1) Establish a cohort of middle-to-older age AA adults (N=300) and use stakeholder‑informed research design and modeling to understand environmental, sociodemographic, and resource barriers related to AD risk, (2) Determine the impact of depression, stress, and a novel, theory-based exposome composite index (CI) on cognitive functioning in participants who are cognitively normal with and without preclinical AD, and (3) Test the association between white matter hyperintensities (WMH) and hippocampal volume (HV) with the exposome-CI in a subset of participants (N=150) with magnetic resonance imaging (MRI) data.
To test our Aims, we have assembled a multidisciplinary team with expertise in AD, exposome, system dynamics, stress and depression, plasma biomarkers, genetics, neuroimaging, neuropsychology, and biostatistical methods. Participants will complete a one-time blood draw for AD biomarker profiling, cognitive assessment using a neuropsychological battery, and participate in one MRI scan session. Participants will also participate in group workshops aiming at identifying combinations of factors influencing AD risk, complete a comprehensive battery of exposome measures mapped onto the National Institute of Aging’s Health Research Framework, and clinical, neurological, and neuropsychological tests annually for up to five years.
Once obtained, this knowledge of how within-group heterogeneity in cognitive functioning and AD risk is impacted by exposome may better support effective AD intervention and treatment for the general population.

Grant Number: 5R01AG074302-05
NIH Institute/Center: NIH
Principal Investigator: Ganesh Babulal