Quantifying the Impact of Environmental Toxicants on Alzheimer's Disease (AD) and AD-Related Dementias (ADRD) Risk in Cohort Studies (U01 Clinical Trial Not Allowed)

Background
The causes of AD/ADRD are multi-factorial in nature, and include factors related to aging, genetics, and the environment. Large scale multi-omic projects have greatly contributed to increasing knowledge of genomic variants and molecular/biological pathways involved in the development of AD/ADRD. However, the role of environmental exposures and their mechanisms that contribute to the pathogenesis of sporadic AD/ADRD remains an area of research that requires further exploration.

The evaluation of environmental exposures has been limited due, in part, to the variation of the methods of measuring environmental exposures, the number of exposures, the multiple sources of exposures, and rarity of certain exposures. Importantly, exposures earlier in life are likely to take decades to impact risk of developing AD/ADRD, and this adds a level of complexity to exposure research.

Classes of toxicants and chemicals that are persistent in the environment and accumulate in humans, such as toxic metals, per- and polyfluorinated alkyl substances (PFAS), industrial chemical mixtures, and contaminants from other sources, represent novel or understudied human exposures where research regarding their potential to increase the risk for AD/ADRD is needed. With evidence that environmental factors are contributors to AD/ADRD, well-designed epidemiology studies will play a key role in the evaluation of health effects from environmental toxicants and will be highly informative in drawing conclusions regarding these risks to human health.

In addition, the impact of the chemical/toxicant exposure on disparities of AD/ADRD is not well understood. Consequently, the paucity of a robust epidemiologic literature translates to a substantial need for studies that could help clarify the etiologic role of environmental toxicants on AD/ADRD development. Further, understanding exposures within real-world environmental settings and the subsequent health effects will require close collaboration across different scientific fields, particularly toxicology, epidemiology, exposure science, risk assessment and statistics, and proper integration of data from each of these disciplines.

Grant Details
This funding opportunity aims to enrich existing longitudinal cohorts with measures of exposures to individual toxicants or combinations of toxicants; support the development of multi-disciplinary teams needed for rigorous measurement and assessment of environmental exposures at the population level; create an environmental epidemiology consortium to facilitate rapid and broad data sharing; harmonization; integration of complex exposure data across multiple studies; enhance data pooling; data integration for various meta-analyses; comparative analyses; promote collaborative research to support addition of environmental exposure measures to well-phenotyped longitudinal AD/ADRD cohorts; addition of AD outcome/biomarker measurements to non-AD/ADRD cohorts with individuals spanning early mid-life (age 30-50) enriched with exposure measurements and measurements of AD biomarkers; investigate differences in response to toxicants by sex if possible.

Eligibility Requirements
Eligible applicants include higher education institutions; public/state controlled institutions; private institutions; nonprofits with 501(c)(3) IRS status (other than institutions); for-profit organizations (including small businesses); local governments; state governments; county governments; city or township governments; special district governments; Indian/Native American tribal governments (federally recognized); Indian/Native American tribal governments (other than federally recognized); federal government agencies; U.S. territory or possession agencies; independent school districts; public housing authorities/Indian housing authorities; Native American tribal organizations (other than federally recognized tribal governments); faith-based or community-based organizations; regional organizations; non-domestic (non-U.S.) entities (foreign institutions).

Period of Performance
The period of performance is over 5 years with an earliest start date in October 2023.

Grant Value
NIA intends to commit $11 million in fiscal year 2024 to support 4-5 awards. Application budgets are limited to $1.5 million in direct costs per year over 5 years.