Practical considerations for characterization of the external exposome in Alzheimer's disease and related dementias cohorts.

External exposome research offers opportunities to evaluate complex relationships between multiple environmental determinants of Alzheimer's disease and related dementias (ADRD). However, selecting specific exposure domains, identifying metrics, and downloading, processing, and managing big data are key challenges in translating the potential of exposome research into empirical data analyses. To overcome these issues, we have established a reproducible system that protects data privacy, setting the stage for an unparalleled examination of associations between environmental exposures and ADRD risk within an exposome framework. In this perspective, we provide a comprehensive guide, including examples, to linking natural, built, and social environment metrics to nationwide time-varying participants' residential address data. Further, as a proof of concept, we report descriptive statistics and spatial distribution of external exposome metrics across the contiguous United States in 2015. The external exposome can be securely and comprehensively characterized across multiple cohorts using this highly scalable approach.