# The Macrovascular and Microvascular Contributions to Alzheimer's Disease: MESA VASCAD

> **NIH NIH R01** · WAKE FOREST UNIVERSITY HEALTH SCIENCES · 2020 · $773,098

## Abstract

Project Summary
Improving vascular health for delaying the onset of Alzheimer’s disease (AD) is identified as a critical goal by
the Alzheimer’s Disease and Related Dementias Conference, the 2015 NIA AD Summit and PAR-15-356 (to
which this application is responding). Yet, critical barriers exist to implementing vascular prevention strategies
for AD, and elucidating the role of midlife metabolic, macro- and micro- vascular factors in AD is essential to
addressing these barriers. Each type of factor may manifest different pathologies in the brain that contribute to
dementia sub-types, making a new and sufficiently comprehensive clinical trial a costly and time-consuming
undertaking. To address this essential gap, we propose to leverage the rich longitudinal cohort data from the
Multi-Ethnic Study of Atherosclerosis (MESA) study with the addition of detailed cognitive testing and
multimodal brain neuroimaging – the MESA VASCAD study. MESA participants at the Wake Forest site (46%
African-American, 54% non-Hispanic Caucasian) have already undergone extensive metabolic and vascular
phenotyping, repeated retinal imaging and a brief cognitive assessment in 2010-2012. The MESA VASCAD
study will add clinical and cognitive assessments (Uniform Data Set and supplemental cognitive tests);
neuroimaging (MRI, amyloid PET); and reanalysis of retinal images. We propose to enroll 540 MESA
participants in 2 years and repeat assessments 3 years later to more fully characterize targeted, modifiable
vascular risk factors for AD. Through our Specific Aims, we will (1) test the hypothesis that baseline
macrovascular and microvascular biomarkers in middle-age predict both standard AD neuroimaging outcomes
(e.g. hippocampal volume and amyloid deposition assessed with PET) and more novel cerebrovascular
biomarkers (e.g. microinfarcts, lacunar infarcts, neurite density and cerebral microbleeds); (2) determine if
changes in metabolic and vascular biomarkers over 15 years predict cognitive and AD biomarker trajectory;
and (3) using high-dimensional machine learning approaches, determine common, differential and interactive
metabolic and vascular risk factor profiles among racial and APOE genotype groups. This proposed ancillary
study, approved by the MESA Steering Committee, is led by a New Investigator with an experienced, multi-
disciplinary team of collaborators. The MESA study is an ideal cohort for interrogating the questions in this
proposal: it has highly detailed longitudinal risk factor data collected over 15+ years in a diverse cohort, which
we can leverage and augment with cerebrovascular biomarkers, AD biomarkers, and cognitive reassessments
- thereby creating a comprehensive brain phenotype dataset for vascular and AD risk factors. These new
data will enable us to examine the timing and impact of vascular biomarkers on dementia biomarkers and
cognitive trajectories before a diagnosis of pre-clinical and clinical AD-related disorders, meeting a critical gap
in in...

## Key facts

- **NIH application ID:** 9928377
- **Project number:** 5R01AG054069-05
- **Recipient organization:** WAKE FOREST UNIVERSITY HEALTH SCIENCES
- **Principal Investigator:** Timothy M. Hughes
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $773,098
- **Award type:** 5
- **Project period:** 2016-09-01 → 2023-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9928377

## Citation

> US National Institutes of Health, RePORTER application 9928377, The Macrovascular and Microvascular Contributions to Alzheimer's Disease: MESA VASCAD (5R01AG054069-05). Retrieved via AI Analytics 2026-06-02 from https://api.ai-analytics.org/grant/nih/9928377. Licensed CC0.

---

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