Investigating neighborhood-environment contributions to midlife risk for dementia

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PROJECT SUMMARY / ABSTRACT Older adults living in disadvantaged neighborhoods, marked by poor physical, social, and economic conditions, are at elevated risk for dementia regardless of their personal sociodemographic characteristics. It is not yet clear when in the lifespan such risk emerges or through which putative causal mechanisms, if it is indeed causal. The activities proposed in this application will fill key research gaps in environmental health and geroscience through first-ever longitudinal studies of neighborhood characteristics and brain aging in midlife, when it is still possible to intervene to prevent dementia. They will inform the identification of at-risk individuals and significantly advance the evidence base needed for potential neighborhood-level dementia interventions, which could leverage public resources outside the healthcare sector and operate without requiring individual behavior change. Proposed projects will integrate diverse geospatial neighborhood data (housed at Michigan State University) into the four-decade archives of the Dunedin Study of psychosocial health, development, and aging among a population-representative New Zealand-based cohort born in 1972 and followed to midlife. The Dunedin cohort is the only one in the world with fine-grained measures of brain integrity from infancy to midlife, with the latest assessment (age 45) including brain structural and functional antecedents of dementia. Studies will determine: (1) whether individuals living in disadvantaged neighborhoods demonstrate signs of accelerated brain aging by midlife; (2) if specific neighborhood characteristics are uniquely associated with midlife brain- health deficits; and (3) whether pro-degenerative health behaviors and conditions (e.g., low physical activity, hypertension, etc.) and are more common in disadvantaged settings and thus may act as causal meditators. The applicant’s career goal is to become a clinical neuropsychologist and independent academic researcher who conducts public health-oriented research on the degenerative consequences of environmental exposures in the hopes of identifying modifiable risk factors and unique interventions to lower the global burden of brain disease. This fellowship will leverage a multi-university training plan to significantly advance the applicant’s career by allowing him to: (1) enter a PI-role in the Dunedin Study; (2) gain additional training to advance his unique research goals, including in established and cutting-edge methods in geospatial analysis, neurotoxicant assessment, and premorbid modeling of brain aging and dementia; and (3) prepare for an innovative career bridging environmental health and psychology with job-readiness skills in teaching, mentoring, and grant writing and management. Mentored training will occur in psychiatric, geospatial, and environmental epidemiology labs at Duke, Michigan State, and Harvard, supplemented by coursework, workshops, and conferences. The fellowship will ensure the applicant's move to independence for a unique body of work investigating environmental contributions to pathological brain aging, with future steps involving additional data linkage and assessment in older and younger cohorts and at the next assessment phase of the Dunedin Study.