# Subclinical Vascular Contributions to Alzheimer's Disease: The Multi-Ethnic Study of Atherosclerosis (MESA) Multisite Study of AD (Renewal)

> **NIH NIH R01** · WAKE FOREST UNIVERSITY HEALTH SCIENCES · 2024 · $4,759,428

## Abstract

PROJECT SUMMARY / ABSTRACT
 This competitive renewal of “MESA-MIND” (R01AG058969) is a cooperative and multi-disciplinary project
ideally positioned to fill critical gaps in our understanding of both the vascular contributions to cognitive
impairment and dementia (VCID) in context of Alzheimer’s disease (AD) and related disorders (ADRD) and the
noted the health disparities in VCID and AD/ADRD. This project is an extension of the Multi-Ethnic Study of
Atherosclerosis (MESA), a large multi-ethnic cohort of 6814 adults now 65 and older (self-reported: 38% White,
28% Black, 22% Hispanic, and 12% Chinese Americans) with deep subclinical vascular phenotyping and stored
plasma over the past two decades. Through initiation of MESA-MIND’s cognitive and imaging visits, we have
demonstrated excellent feasibility to recruit MESA participants into a multimodal and multilingual ADRD research
study more than 15 years after MESA baseline. The primary focus of MESA-MIND remains to define the
subclinical vascular contributions to changes in AD/ADRD biomarkers and cognitive phenotypes of impairment.
In MESA-MIND, we have shown that subclinical biomarkers of arteriosclerosis and atherosclerosis were
associated with imaging biomarkers (MRI and PET), cognitive decline, and cognitive impairment. These
peripheral vascular and imaging biomarkers of vascular disease tend to be higher in men, as well as self-reported
Black and Hispanic older adults; differences that were partially explained by social determinants of health. MESA
has recently built the infrastructure to define the temporal sequence of molecular dysregulation with longitudinal
plasma AD biomarkers and ‘omics data over two decades. This renewal cycle seeks to make major strides in
our mechanistic understanding of structural, functional, and molecular drivers of “subclinical VCID” by: (1)
leveraging MESA’s longitudinal and extensive subclinical vascular biomarkers paired with recent advancements
in high-throughput plasma AD biomarkers, proteomics and metabolomics technologies applied to MESA and (2)
expanding these data resources through two new exams (“MIND C” and “MIND D”) over the next 5 years. These
new resources will enable examination of the molecular (genomic, proteomic, and metabolomic) aspects shared
by vascular disorders, AD biomarkers, and cognitive phenotypes as well as the temporal sequence of transition
from subclinical disease to clinical phenotype. Each research question in MESA-MIND is designed to consider
the consistency of subgroup analyses by gender, racial, and ethnic groups to characterize the health disparities
in VCID/AD/ADRD in the context of social determinants of health.

## Key facts

- **NIH application ID:** 10885534
- **Project number:** 2R01AG058969-06
- **Recipient organization:** WAKE FOREST UNIVERSITY HEALTH SCIENCES
- **Principal Investigator:** Timothy M. Hughes
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $4,759,428
- **Award type:** 2
- **Project period:** 2018-08-15 → 2029-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10885534

## Citation

> US National Institutes of Health, RePORTER application 10885534, Subclinical Vascular Contributions to Alzheimer's Disease: The Multi-Ethnic Study of Atherosclerosis (MESA) Multisite Study of AD (Renewal) (2R01AG058969-06). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10885534. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*