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

> **NIH NIH R01** · WAKE FOREST UNIVERSITY HEALTH SCIENCES · 2022 · $3,776,527

## Abstract

Project Summary
Improving vascular health is a critical potential strategy to delay the onset of Alzheimer's disease
(AD). However, there are few vascular targets as the specific mechanisms linking vascular
dysfunction to AD remain unclear. Racial/ethnic minority groups in the United States have a higher
vascular burden and more than a two-fold risk of developing Alzheimer's disease (AD). Further,
recent data has confirmed that African-Americans also have a greater risk of having higher cerebral
β-amyloid (Aβ) burden than Whites. Yet, little work has been done to characterize the increased risk
for AD among different racial/ethnic groups and little is known about `why' they carry a greater risk for
AD. Arterial stiffness is emerging as a key vascular risk factor for late life dementia, through
associations with various aspects of AD-related pathology including: cerebral small vessel disease, β-
amyloid deposition and brain atrophy in AD-prone regions. However, gaps in our understanding of
this mechanism remain. To date, no existing studies have adequate data to directly connect arterial
stiffness to aspects of AD pathology through its effects on cerebral blood flow or to evaluate the
association in a multi-ethnic cohort. We propose to address these gaps in our knowledge by
leveraging >15 years of highly detailed and unparalleled longitudinal vascular data from Multi-Ethnic
Study of Atherosclerosis (MESA). The `MESA Multisite AD study' will add: a) repeated, detailed
cognitive assessments to adjudicate cognition and assess cognitive changes over time; b) repeated
MRIs to assess neurodegeneration, cerebrovascular disease and cerebral perfusion; and d) Aβ-PET
imaging to quantify Aβ burden. The `MESA Multisite AD study' will contribute key findings and unique
resources relating antecedent subclinical vascular disorders to AD pathology and cognitive decline.
Specifically, it will address the role of changes arterial stiffness and hemodynamic pathways to AD-
related pathology. This approach will be an efficient and cost-effective open-resource for researchers
to identify antecedent modifiable vascular and metabolic risk factors (over >15 years) for AD and will
help guide the development of novel therapeutic targets or prevention strategies for various forms of
AD-related dementias.

## Key facts

- **NIH application ID:** 10424409
- **Project number:** 5R01AG058969-05
- **Recipient organization:** WAKE FOREST UNIVERSITY HEALTH SCIENCES
- **Principal Investigator:** Kathleen M Hayden
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $3,776,527
- **Award type:** 5
- **Project period:** 2018-08-15 → 2024-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10424409

## Citation

> US National Institutes of Health, RePORTER application 10424409, Subclinical Vascular Contributions to Alzheimer's Disease:  The Multi Ethnic Study of Atherosclerosis (MESA) Multisite Studyof AD (5R01AG058969-05). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10424409. Licensed CC0.

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