PROJECT SUMMARY/ABSTRACT Alzheimer’s disease and related dementias (AD/ADRD) are a growing public health burden and understanding the causes of AD/ADRD is a national priority. Environmental factors, such as metals exposure, are an understudied area of the exposome, and may contribute to higher risk of cognitive impairment and AD/ADRD. Prospective longitudinal data on incident AD/ADRD, as available in the Health and Retirement Study (HRS), provide the best outcome measures to pair with measures of exposure. This supplemental proposal aims to add to the rich HRS data on longitudinal contextual and socioeconomic risk factors for AD/ADRD by directly measuring blood heavy metals concentrations in 13,500 participants, and share the data with the research community using established HRS data-sharing systems to enable examination of associations with incident AD/ADRD. We will use energy-dispersive X-ray fluorescence (EDXRF) to measure lead, cadmium, mercury and arsenic in repository dried blood spots (DBS) from 2006-2012 (N=13,500) and use cutting edge methods to identify metal mixture patterns. We will also calibrate DBS EDXRF measurements with venous blood gold standard methods in a unique sample of persons with both DBS and venous blood taken in 2016 (N=1,500). The completion of this supplement will generate one of the largest, representative and racially diverse studies of heavy metals and AD/ADRD to date, and significantly increase the resources available to researchers from multiple disciplines to better identify the impact of metals exposure on AD/ADRD risk.

PROJECT NARRATIVE This supplemental proposal aims to add to the rich Health and Retirement Study (HRS) data on longitudinal contextual and socioeconomic risk factors for Alzheimer’s disease and related dementias (AD/ADRD) by directly measuring blood heavy metals concentrations in 13,500 participants, and sharing the data with the research community using established HRS data-sharing systems to enable examination of associations with incident AD/ADRD. We will use energy-dispersive X-ray fluorescence (EDXRF) to measure lead, cadmium, mercury and arsenic in repository dried blood spots (DBS) from 2006-2012 (N=13,500) and use cutting edge methods to identify metal mixture patterns. We will also calibrate DBS EDXRF measurements with venous blood gold standard methods in a unique sample of persons with both DBS and venous blood taken in 2016 (N=1,500).