Rural microvascular contributions to neurocognitive decline

The National Institute on Aging awarded The University of Texas Health Science Center at San Antonio $2,147,145 on September 15, 2026, under the Aging Research program (CFDA 93.866) to conduct the Rural Microvascular Contributions to Neurocognitive Decline (RURAL-MIND) study.

The study deploys portable MRI neuroimaging, AI-driven image analytics, repeated plasma biomarker profiling, and longitudinal cognitive assessments across 4,000 rural residents in high- and lower-risk counties to investigate how vascular risk factors shape brain aging, plasma biomarker changes, and cognitive decline in rural America. The research addresses disproportionately high dementia risk, vascular disease burden, and premature mortality in rural areas, particularly Appalachia and the Mississippi Delta, by characterizing the structural brain changes and biomarker profiles underlying these disparities. The study leverages existing infrastructure from the NHLBI-funded Risk Underlying Rural Areas Longitudinal (RURAL) cohort and its mobile examination unit, which has delivered state-of-the-art clinical assessments and imaging to remote communities since 2020.

Work is performed in San Antonio, Texas, with a period of performance from September 15, 2026, through August 31, 2027. The award is structured as a Project Grant, the standard assistance type for investigator-initiated research under the National Institute on Aging's Aging Research program, which emphasizes prevention and treatment of Alzheimer's disease and related dementias.

Abstract

Dementia risk factors, vascular disease burden, and premature mortality are disproportionately high in RURAL america, especially in appalachia and the mississippi delta. Yet, the structural brain changes and biomarker profiles that underlie these disparities remain essentially uncharacterized because RURAL communities lack access to advanced neurodiagnostic resources. We anticipate that vascular contributions to cognitive impairment and dementia (VCID) play a large role in the risk for alzheimer's disease and related dementias (ADRD) in RURAL areas, with mixed alzheimer's and cerebrovascular pathology representing the dominant neurodegenerative profile in older adults. Small vessel disease (SVD), an actionable and highly prevalent pathology, is tightly linked to modifiable vascular and metabolic risk factors that are elevated in RURAL populations. Understanding how these risk factors shape brain aging, plasma biomarker changes, and cognitive decline in RURAL america is, therefore, a critical public health priority. Our study leverages the unique infrastructure of the nhlbi-funded risk underlying RURAL areas longitudinal (RURAL) cohort and its novel mobile examination unit (MEU), which has brought state-of-the-art clinical assessments and imaging directly to remote communities since 2020. The RURAL microvascular contributions to neurocognitive decline (RURAL-MIND) study will leverage and extend RURAL infrastructure in the ADRD space by deploying portable MRI neuroimaging, advanced AI-driven image analytics, repeated plasma biomarker profiling, and longitudinal cognitive assessments in 4,000 RURAL residents across high- and lower-risk counties carefully matched on population composition and economic indicators. This ecologically paired deployment enables representative sampling of RURAL regions with differing cardiovascular and mortality burdens, ensuring a scientifically rigorous evaluation of how environmental, community, and biological factors interact to shape dementia risk through VCID and ADRD. Aim 1 will characterize structural brain changes, including atrophy, brain age, and markers of SVD, using portable MRI, and determine their associations with cognition and dementia. Aim 2 will evaluate how structural MRI abnormalities relate to antecedent changes in plasma biomarkers measured ~5 years apart (P-TAU, NFL, gfap, inflammatory cytokines), revealing a correlation between neuronal injury, neurodegeneration, and vascular brain damage. Aim 3 will integrate vascular/metabolic risk factors, MRI markers, plasma biomarkers, and longitudinal cognition using structural equation modeling and counterfactual mediation to identify mechanistic pathways driving cognitive decline and dementia. Impact: RURAL-MIND will generate the first large-scale, neuroimaging-based dementia risk model in RURAL america, using methods scalable to any remote or RURAL setting. By uniting portable MRI, advanced AI neuroimaging, and repeated biomarker profiling within an ecologically representative RURAL cohort, RURAL-MIND will illuminate biological pathways underlying RURAL cognitive aging and provide actionable targets for early detection, prevention, and intervention strategies aimed at reducing ADRD disparities nationwide.