The Legacy of Childhood SES and Lead Exposure on Dementia Risk: ARIC-NCS Historical Census Linkage - SUMMARY/ABSTRACT Risk for Alzheimer’s Disease and AD-related dementia (ADRD) in late life is sensitive to social and environmental exposures in childhood—a critical period of brain development. Children who grow up in families and neighborhoods with few socioeconomic resources and those who are exposed to lead (Pb; a potent neurotoxicant) in their environment may have higher risk of ADRD as they age. However, evidence supporting these associations is limited by retrospective recall of childhood conditions and/or small, non-population based samples. Furthermore, the pathways underpinning these relationships are unclear. We propose to create a novel data source for conducting research on early life origins of ADRD by linking participants of the Atherosclerosis Risk in Communities Neurocognitive Study (ARIC-NCS; N=15,792) to their household records in the 1930, 1940, and 1950 U.S. Censuses, which occurred when they were children. The overall objectives of this project are to (a) provide prospective estimates for the independent and synergistic effects of childhood SES and Pb exposure on later life ADRD incidence, (b) examine how these early life exposures contribute to ADRD etiology using data from brain imaging scans (beta-amyloid from PET, vascular disease from MRI) and plasma biomarkers of neurodegeneration, and (c) investigate how these relationships are mediated across the life course using >35 years of prospectively collected ARIC data. We will also (d) examine the consistency of these relationships by race and sex. This project has four specific aims: (Aim 1) Investigate the relationship of childhood individual- and neighborhood-level socioeconomic resources with risk of incident ADRD and biomarkers of neuropathology. Census-derived measures of family SES were reported by participants’ parents. Using full-count Census data, we will also construct aggregate measures of SES in participants’ childhood neighborhoods. (Aim 2) Investigate the relationship between childhood Pb exposure and incident ADRD and biomarkers of neuropathology. We will accomplish this by using historic data on Pb exposure through water (Pb plumbing and water acidity), Pb gasoline (automotive and aviation) and Pb mines and smelters. (Aim 3) Examine whether childhood SES modifies the association between Pb exposure and incident ADRD. (Aim 4) Create infrastructure for future explorations using census-linked ARIC-NCS data. This Aim will support the secure, efficient, and reproducible use of these novel early-life data for future investigations by the broader research community. This project is innovative because it will rely on contemporaneous rather than retrospective measurement of childhood circumstances, evaluate incident ADRD in a diverse population, and provide etiologic insights using the deeply phenotyped ARIC-NCS data. The proposed research is significant because it will consequentially improve our understanding of the connections between early-life socioeconomic disadvantage, Pb exposure, and ADRD risk in late-life, which may inform policy and future interventions.
