Add Health as a Resource for the Science of the Exposome and Risk for AD/ADRD

Project Summary This supplement to U01 AG071450 responds to NOT-AG-22-022, which lays out the “urgent need for research infrastructure that addresses the role of diverse physical, chemical, social, psychological, and economic exposures across multiple levels and across the life course in the etiology and social disparities of Alzheimer’s

disease (AD) and AD-related dementias (ADRD).” Our overall objective is to better position the National Longitudinal Study of Adolescent to Adult Health (Add Health) as a central resource for scientists to more effectively operationalize and study the exposome and its consequences for cognitive function, cognitive decline,

and the progression of AD/ADRD across the life course, with particular attention to disparities across population subgroups. Given currently available exposure data in Waves I-V of Add Health and the timing of Wave VI fieldwork, our first two aims will substantially strengthen Add Health’s social and health contextual data and

vastly expand our environmental contextual data, respectively. Doing so is in direct support of Add Health becoming a key resource for the operationalization of the exposome and for understanding AD/ADRD-related outcomes and disparities. The third aim will add SARS CoV-2 infection antibody data to our array of assays.

Given the now widespread prevalence of COVID-19 infection in the general population and the potential long- term importance of COVID-19 exposure for cognitive functioning and risk for AD/ADRD, it is critical to include such data to best position Add Health as an extraordinarily rich longitudinal study to operationalize the exposome.

Specific aims of the supplement are: 1) To assemble, merge, document, and disseminate rich social- and health- related contextual data to Add Health participant residences from Wave I through Wave VI. We will complement our previous and ongoing efforts in this realm by focusing on the domains of structural racism, structural sexism,

structural heterosexism, structural xenophobia, and health inequality. 2) To estimate, document, and disseminate key natural, physical, and chemical environmental exposures at accurately geopositioned/geocoded Add Health participant residences from Wave I through Wave VI. We will focus on the environmental, natural, and built

domains specific to participants’ locations. 3) In recognition of the critical role of the ongoing COVID-19 pandemic and the impact of this infection on the exposome and AD/ADRD-related risk factors, we will test 7,500 Add Health Wave VI participants for antibodies to SARS CoV-2 infection. These biomarkers of infection will augment a large,

accessible array of existing biomarkers in Add Health, including arrays of epigenomic, transcriptomic, and microbiome measures plus inflammatory, infectious, and neuroimmune biomarkers of AD/ADRD. Together, accomplishing these aims will greatly enhance the research capacity of Add Health to understand the social,

health, environmental, and biologically based dimensions of the exposome and how they contribute to cognitive function, cognitive decline, risk of AD/ADRD, and disparities therein.