# Development of MRI microvascular biomarkers in cognitive impairment and dementia

> **NIH NIH UH3** · JOHNS HOPKINS UNIVERSITY · 2020 · $1,154,399

## Abstract

Project Summary/Abstract:
 Small vessel cerebrovascular disease is a major risk factor in Alzheimer’s disease. However, quantitative
biomarkers that are suitable for use as endpoints in clinical trials for these conditions are still lacking. The goals
of the present project are to 1) in the UH2 phase, evaluate and identify MRI-based microvascular biomarkers
that are diagnostic and predictive, with a particular focus on a novel marker referred to as cerebrovascular
reactivity; 2) in the UH3 phase, work with the Coordinating Center and other projects in the consortium to
further evaluate the most promising biomarker candidates in a multi-site setting.
 Conventional anatomic imaging (e.g. T2-FLAIR) can identify white matter hyperintensities that represent
the consequence of small vessel damage. In this project, we will emphasize several newer techniques that
probe the potential physiological driving force of small vessel cognitive impairment and dementia (VCID).
Specifically, we will focus on a marker indexing the dynamic coupling capacity of the neurovascular unit,
referred to here as cerebrovascular reactivity (CVR). Our previously studies on CVR have revealed that: 1)
CVR is three times as sensitive to age as resting perfusion. 2) CVR is diminished in patients with AD dementia.
3) Decline in processing speed (over four years) is significantly associated with CVR decline (over four years).
4) CVR of the brain is strongly correlated with structural lesions as seen on T2-FLAIR. Therefore, the present
project will emphasize the development of CVR MRI as a small vessel imaging biomarker, with additional
consideration of several other microvascular parameters including microbleeds count and cerebral blood flow
(CBF). These small vessel measures (vascular imaging markers) will be combined into a composite index
based on their contributions to cognitive impairment, which will form a composite imaging biomarker for
diagnosis, prediction, and target engagement of VCID.
 Our Specific Aims in the UH2 phase are: 1) Examine the association between cognitive function and
candidate vascular imaging markers in a group of elderly individuals with mixed vascular and Alzheimer’s
pathology; 2) Conduct technical assessment of the vascular imaging methods to show that they are multi-site
ready in terms of applicability and reproducibility; 3) Work with Coordinating Center and other Development
Projects to establish the consortium in preparation for the UH3 phase. Quantifiable milestones have been
defined for these aims and for the readiness of the project to enter the UH3 phase, in which the specific aim is
to perform collaborative studies as part of the small vessel biomarker consortium to further evaluate and
develop the most promising biomarker candidates.
 Impact: Upon the completion of this project, we will have developed a small vessel imaging biomarker that
is ready for large scale multi-site clinical validation studies.

## Key facts

- **NIH application ID:** 10001049
- **Project number:** 5UH3NS100588-05
- **Recipient organization:** JOHNS HOPKINS UNIVERSITY
- **Principal Investigator:** MARILYN S. ALBERT
- **Activity code:** UH3 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $1,154,399
- **Award type:** 5
- **Project period:** 2016-09-30 → 2021-09-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10001049

## Citation

> US National Institutes of Health, RePORTER application 10001049, Development of MRI microvascular biomarkers in cognitive impairment and dementia (5UH3NS100588-05). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10001049. Licensed CC0.

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