# Multimodal MRI biomarkers of small vessel disease for older persons with and without dementia.

> **NIH NIH UH3** · RUSH UNIVERSITY MEDICAL CENTER · 2020 · $1,159,758

## Abstract

ABSTRACT
Small vessel disease (SVD) pathologies are very common in the brains of older persons and are related to
decline in cognitive abilities, MCI, and dementia. SVD pathologies include three common vessel diseases and
an array of related tissue injuries. SVD pathologies may cause dementia on their own but more commonly
coexist with Alzheimer's disease (AD) and other age-related pathologies where they lower the threshold for
dementia. Effective participant selection into trials, and prevention and treatment would greatly benefit from
having in-vivo biomarkers of this pathology. Current biomarkers are limited by lack of specificity for SVD (vs.
AD) pathology and lack of pathologic validation. We propose to overcome these obstacles by (1) further
developing specific ex-vivo MR imaging features of SVD pathologies after controlling for AD and other
pathologies, in the brains of persons with and without dementia; (2) training a classifier using machine learning
and multimodal MRI, and testing the classifier in persons without dementia, and whether it is related to
cognitive status proximate to death; (3) translating the classifier into an in-vivo biomarker which can be
investigated in relation to vascular risk factors and cognition, MCI, and dementia; and (4) validating the
biomarker in a separate cohort (ADNI) and by autopsy confirmation of SVD pathologies in a large group of
older persons followed longitudinally with MRI who agree to autopsy at death. Finally we propose to (5) share
data, expertise and biomarker strategies within the UH2/UH3 consortium and cross-validate selected
biomarkers in older persons followed longitudinally with cognitive testing, blood draws and brain autopsy at the
time of death. We propose to leverage the resources of two longitudinal clinical-imaging-pathology cohorts,
the Rush Memory and Aging Project (MAP) (R01AG017917) and Religious Orders Study (ROS)
(P30AG010161), to accomplish these aims.

## Key facts

- **NIH application ID:** 9995038
- **Project number:** 5UH3NS100599-05
- **Recipient organization:** RUSH UNIVERSITY MEDICAL CENTER
- **Principal Investigator:** Konstantinos Arfanakis
- **Activity code:** UH3 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $1,159,758
- **Award type:** 5
- **Project period:** 2016-09-30 → 2021-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9995038

## Citation

> US National Institutes of Health, RePORTER application 9995038, Multimodal MRI biomarkers of small vessel disease for older persons with and without dementia. (5UH3NS100599-05). Retrieved via AI Analytics 2026-06-01 from https://api.ai-analytics.org/grant/nih/9995038. Licensed CC0.

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