# MRI and CSF Biomarkers of White Matter Injury in VCID

> **NIH NIH UH3** · UNIVERSITY OF NEW MEXICO HEALTH SCIS CTR · 2020 · $1,105,721

## Abstract

Summary/Abstract
 Vascular cognitive impairment dementia (VCID) is a heterogeneous disease that is an important cause
of dementia. This proposal is in response to a RFA to identify biomarkers to separate patients into subgroups
for treatment trials. Although much is known about multiple biomarkers individually, there is a major gap in our
understanding of the optimal ones to use in collaborative studies, which is the aim of this proposal. Subcortical
ischemic vascular disease (SIVD) is the progressive small vessel disease (SVD) form that is optimal for
treatment trials. MRI modalities and CSF biochemical studies provide the most promising biomarkers. White
matter damage is the hallmark of SIVD, and MRI is the optimal method to show the progressive changes.
Biochemical studies of CSF show the inflammatory biomarkers of albumin, matrix metaloproteinases (MMPs)
and cytokines. In an on-going clinical study of SIVD, our group has identified microstructural studies with MRI
and biochemical studies of MMPs in the CSF as the two most promising biomarkers. This two-phase,
milestone-driven proposal is to identify the optimal microstructural and biochemical biomarkers to both identify
the SIVD subgroup and to use as surrogate markers of progression. In the first U2 phase, the optimal method
to measure CSF MMPs will be determined for patient classification and the optimal MRI biomarkers to show
progression will be determined. Normal-appearing white matter (NAWM), which is a region with normal FLAIR
signal, often has abnormal diffusion signals, indicating tissue at risk (prodromal). The hypothesis is that CSF
and MRI biomarkers can be used for classification of SIVD patients with CSF for primarily classification
and MRI for both classification and as a surrogate marker for predicting disease progression that can
be used for patient treatment decisions. There are three specific aims: 1) to demonstrate that the growth of
white matter hyperintensities (WMHs) as defined by FLAIR images can be predicted based on biomarkers
calculated from multi-shell, high b-value diffusion MRI (dMRI); 2) to identify functional brain connectivity,
structural brain connectivity and gray matter atrophy biomarkers that predict cognitive decline (executive and
memory function) in VCID subjects over a period of two to three years; and, 3) to compare MMP
measurements made with zymography with two novel methods, including an ELISA-based method and an
activity assay based on immunocapture and fluorescent peptide cleavage in order to optimize the biochemical
studies. This proposal will fill a gap in knowledge as to the optimal biomarkers to use for collaborative studies.
The major aims are related to refining the set of biomarkers for patient selection, which will be done in the U2
phase by increasing the size of the existing University of New Mexico (UNM) cohort from 100 to 200 patients,
and to perform the CSF studies for patient classification and the dMRI studies longitudinally to defin...

## Key facts

- **NIH application ID:** 9989676
- **Project number:** 5UH3NS100598-05
- **Recipient organization:** UNIVERSITY OF NEW MEXICO HEALTH SCIS CTR
- **Principal Investigator:** Gary Allen Rosenberg
- **Activity code:** UH3 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $1,105,721
- **Award type:** 5
- **Project period:** 2016-09-30 → 2021-09-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9989676

## Citation

> US National Institutes of Health, RePORTER application 9989676, MRI and CSF Biomarkers of White Matter Injury in VCID (5UH3NS100598-05). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/9989676. Licensed CC0.

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