# Physiological imaging markers in vascular contributions to cognitive impairment and dementia (VCID)

> **NIH NIH R01** · JOHNS HOPKINS UNIVERSITY · 2024 · $778,738

## Abstract

Project Summary/Abstract: Small-vessel-related vascular contributions to cognitive impairment and dementia
(VCID) represent the second leading cause of cognitive dysfunction in older individuals. However, quantitative
measures indexing key vascular processes related to VCID that are suitable for use as diagnostic biomarkers
or endpoints in clinical trials are still lacking. In particular, biomarkers are playing an increasingly important role
in biological/etiological classification of patients with Alzheimer’s Disease and Related Dementias (ADRD),
following the development of the “A/T/N” classification system. However, the current “A/T/N” scheme is only
applicable to dementia of AD type. Therefore, the development of a biomarker to extend the “A/T/N”
classification scheme to “A/T/N/V” is of potentially high impact.
 Cerebral physiological parameters can report key process leading to the pathological cascade in the brain
and usually occur early in disease. Drugs that can alter physiological process such as perfusion are also
readily available. Therefore, a physiology-based biomarker in VCID will have a major impact on the diagnosis
and treatment selection/monitoring of patients with vascular cognitive impairment, vascular dementia, or mixed
dementia which are common in ADRD. The PI’s lab recently pioneered a non-invasive MRI technique to
measure the oxygen extraction fraction (OEF) of the brain, a parameter indexing the balance between
oxygen supply and consumption, with a scan time of merely one and a half minutes. Our preliminary studies
provided strong evidence that elevated OEF is a physiological hallmark of VCID and tracks the progression of
vascular risks and the growth in white-matter-hyperintensity (WMH) volume. Therefore, the central hypothesis
of this project is that OEF is a sensitive and practical marker in classifying “V” in the A/T/N/V system.
 This project has three Aims. Aim 1 will examine the cross-sectional relationship of OEF with vascular
abnormalities on MRI, cognitive function, and clinical diagnosis in a VCID-enriched cohort. Our novel cohort
will consist of impaired patients (subjective cognitive decline, MCI, and mild dementia) with MRI-confirmed
small vessel abnormalities such as WMH, microbleeds, or lacunar infarcts. Aim 2 will be a longitudinal study
(30-month follow-up) of these participants. Changes in OEF will be studied along with their relationship with
changes in cognitive function and vascular abnormalities. Baseline OEF will also be investigated to examine if
it can predict changes in clinical and cognitive scores. Aim 3 will operationalize the OEF marker to make it
ready for use in clinical/research studies. We will also consider the relationship of OEF with other markers
being tested in the field such as the MarkVCID Study. The PI has assembled an outstanding team of multi-
disciplinary investigators for this project and all of them have worked together previously.

## Key facts

- **NIH application ID:** 10805105
- **Project number:** 1R01AG085299-01
- **Recipient organization:** JOHNS HOPKINS UNIVERSITY
- **Principal Investigator:** Hanzhang Lu
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $778,738
- **Award type:** 1
- **Project period:** 2023-12-05 → 2028-11-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10805105

## Citation

> US National Institutes of Health, RePORTER application 10805105, Physiological imaging markers in vascular contributions to cognitive impairment and dementia (VCID) (1R01AG085299-01). Retrieved via AI Analytics 2026-06-03 from https://api.ai-analytics.org/grant/nih/10805105. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*