# Non-Invasive MRI Markers to Elicit the Role of Vascular Disease in CADASIL Compared to Normal Aging

> **NIH NIH R01** · UNIVERSITY OF WISCONSIN-MADISON · 2024 · $730,685

## Abstract

Project Summary/Abstract:
The project addresses vascular contributions to cognitive impairment and dementia (VCID) using a design that
enrolls persons with the autosomal dominant gene for Cerebral Autosomal Dominant Arteriopathy with
Subcortical Infarcts and Leukoencephalopathy (CADASIL). Exploration of VCID by focusing on the rare heritable
monogenic disorder, CADASIL, will advance knowledge of the full spectrum of this vascular dementia from
asymptomatic gene carriers through dementia and will facilitate studies evaluating vascular contributions in
different neurodegenerative processes including Alzheimer’s disease (AD) and related dementias (ADRD).
CADASIL is caused by a mutation in the gene Notch3, which encodes a receptor protein expressed in vascular
smooth muscle cells and pericytes. When mutated, expression of the gene leads to generalized degeneration of
vascular smooth muscle cells affecting small and medium sized arteries. To provide insights into the impact of
small vessel disease (SVD) in CADASIL (and AD, ADRD, and VCID more generally) on parenchymal damage
and cognitive decline, non-invasive Magnetic Resonance Imaging (MRI) provides quantification of brain
structure, function, and some measures of vascular health; however, current clinically available MRI techniques
lack sensitivity and specificity to address key vascular hypotheses as many measures only indirectly study
cerebrovascular disease, primarily focusing on the damage already caused by SVD, not the vessels themselves.
Our group is uniquely positioned to address these key gaps in our knowledge base, both due to our MRI
technology and as a member of the first CADASIL consortium study in North America. We propose an ensemble
of novel MRI techniques optimized to provide vascular specific measures in a non-invasive imaging protocol. By
characterizing in vivo measures of vascular stiffening at the macrovascular and microvascular levels in CADASIL,
we will provide insights into the degree and mechanisms of VCID and establish baseline data to compare the
longitudinal time course of CADASIL with normal age-related cerebrovascular changes, including SVD. We
previously found that our MRI stiffness measures can detect vascular changes in amyloid positive AD participants
even prior to demonstrating cognitive dysfunction. Our pilot data in CADASIL suggests pronounced vascular
disease involving all levels of the cerebrovascular system. In close collaboration with three additional CADASIL
consortium sites, a multidisciplinary team at the University of Wisconsin will first utilize newly developed, state-
of-the art, quantitative MRI vascular imaging methods to understand the distribution and severity of vascular
changes in CADASIL (Aim 1). We will then study the influence of altered intracranial vasculature on CADASIL
neurodegeneration and cognition (Aim 2), and finally, we will study the degree of vascular involvement in
CADASIL in comparison to cognitively unimpaired, normal aging partic...

## Key facts

- **NIH application ID:** 10806604
- **Project number:** 1R01AG082208-01A1
- **Recipient organization:** UNIVERSITY OF WISCONSIN-MADISON
- **Principal Investigator:** Laura Burns Eisenmenger
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $730,685
- **Award type:** 1
- **Project period:** 2024-02-15 → 2029-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10806604

## Citation

> US National Institutes of Health, RePORTER application 10806604, Non-Invasive MRI Markers to Elicit the Role of Vascular Disease in CADASIL Compared to Normal Aging (1R01AG082208-01A1). Retrieved via AI Analytics 2026-06-02 from https://api.ai-analytics.org/grant/nih/10806604. Licensed CC0.

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