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Operationalizing the neural exposome for brain health and Alzheimer's Disease and Related Dementias (AD/ADRD) vulnerability in rural settings: pilot study

Souza-Talarico, J. N.; Lehmler, H.-J.; Caldwell, J. K.; Cortes, Y.; Zuelsdorff, M.; Fun, Y.; Embree, J.; Doyle, C.; Halverson, K.; Martinez Rangel, M.; Harb, A.; Croskey, O.; Britt, K.; Howland, C.; Capuano, A. W.

2026-06-01 public and global health
10.64898/2026.05.21.26353825 medRxiv
Show abstract

INTRODUCTION: Alzheimers disease and related dementias (AD/ADRD) arise from cumulative environmental, social, behavioral, and biological influences across the life course. The neural exposome framework conceptualizes how exogenous, behavioral, and endogenous factors interact to shape brain health; however, its application to preclinical AD/ADRD research, particularly in rural populations, remains limited. METHODS: We developed and piloted a community-embedded, decentralized research model to operationalize the neural exposome framework among cognitively unimpaired adults aged 45+ in two rural Midwestern U.S. communities, integrating environmental, social, behavioral, geospatial, and biological measures to evaluate exposure-related neurobiological and cognitive vulnerability. RESULTS: This approach demonstrated high feasibility and acceptability, achieving strong recruitment, retention, data completeness, and multidomain biomarker collection in rural community-based settings DISCUSSION: Pilot findings support the feasibility of neural exposome-informed research in rural U.S. communities and highlight its potential to advance prevention-oriented research on brain health and AD/ADRD.

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