Vascular Determinants of Dementia and Cognitive Decline in a Tri-Ethnic Region

Project: Research project

Project Details

Description

Project Summary Cognitive decline and dementia disproportionately burden Black and Hispanic adults resulting in major public health inequities. The National Plan for Alzheimer's Disease and Alzheimer's Disease-Related Dementias (AD/ADRD) has recommended more extensive studies on the risk and determinants of dementia in diverse populations. The Northern Manhattan Study Magnetic Resonance Imaging (MRI) cohort consists of a population-based cohort of 1290 subjects (median age 70 years at MRI; 15% White, 17% Black, 66% Hispanic) from the same community who have been followed annually for a median of 19 years. The cohort is well characterized with a wealth of sociodemographic, lifestyle, social, and vascular risk factor data, and participants underwent standardized brain MRI and 3 intervals of detailed, comprehensive neuropsychological (NP) assessments. The NOMAS cohort is an outstanding resource to address Vascular Cognitive Impairment & Dementia (VCID). Over the last cycle, we adjudicated 4.6% of the population with dementia and 20% with Mild Cognitive Impairment (MCI) with 2-fold greater risk for Black and 4-fold for Hispanic subjects compared to Whites. Our new aims are focused on novel ADRD and VCID risk factors and biomarkers including gut microbiota-derived circulating metabolites, inflammatory and immune networks, cerebral large artery disease (extracranial carotid and intracranial artery disease), and MRI markers of cerebral small vessel disease (white matter hyperintensities, covert infarcts, perivascular spaces, and white matter integrity measures). Additionally, we will evaluate effect modification and mediation with vascular and neurogenerative AD biomarkers. To accomplish these aims, we will continue to follow the MRI cohort with annual telephone contact and a 4th NP assessment to track cognitive trajectories and adjudicate MCI and dementia. Utilizing stored blood, we will measure new gut microbiota-derived circulating metabolites and host immune markers, single molecule array assays for AD serum biomarkers, re-analyze baseline carotid ultrasound and MRIs for large artery disease, evaluate MRI brain imaging phenotypes for small artery disease, and analyze new follow-up MRIs (n=300) for novel small artery disease markers harmonized with the MarkVCID consortium. The innovative strengths of this prospective cohort study are the focus on an at-risk, tri-ethnic population within a single community, the evaluation of the gut-microbiome brain axis and novel neuroimmune networks, the measurements of small and large artery disease biomarkers, and a detailed evaluation of vascular and neurogenerative pathways critical to cognitive decline and dementia. Building on the wealth of cognitive, imaging, and lifestyle data collected in NOMAS over the course of two decades and utilizing innovative statistical approaches, our interdisciplinary team will evaluate novel hypotheses, build a valuable shared data resource, fill important gaps related to ADRD and VCID, and lay the foundation for targeted preventive interventions in diverse populations.
StatusActive
Effective start/end date9/23/218/31/22

Funding

  • National Institute of Neurological Disorders and Stroke: $537,250.00

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