# Cerebrovascular neuroimaging markers and abnormal brain aging

> **NIH NIH F31** · VANDERBILT UNIVERSITY · 2022 · $32,031

## Abstract

PROJECT SUMMARY
It is increasingly recognized that cerebrovascular dysfunction plays an important role in Alzheimer’s disease
(AD) pathogenesis and cognitive decline, contributing to 70% of all dementias. Cerebral small vessel disease
(SVD) often occurs (up to 80%) in those with Alzheimer’s disease (AD), but the current markers of SVD risk
and progression are poor. Cerebrovascular reactivity (CVR) is a neuroimaging marker of vascular health which
indicates of the ability of the brain vessels to respond to neuronal demand or a vasoactive stimulus, such as
inhaled CO2. CVR shows promise as a marker of SVD and cognitive impairment, but some studies fail to see
an association between CVR and markers of abnormal brain aging. Increasing evidence suggests that the time
it takes for brain vessels to maximally respond to a stimulus, or CVRDELAY, may be a more sensitive of
cerebrovascular health than CVR. Further, due to technical and physiological factors, CVR is often only
quantified in the grey matter, and thus associations between white matter CVR and brain health are not well
characterized. Rather than traditional CVR processing which assumes uniformly timed reactivity to CO2 across
the entire brain parenchyma, we propose to use more novel time-delay processing to quantify CVR from
hypercapnic normoxic challenge blood-oxygen-level-dependent functional magnetic resonance imaging
(BOLD-fMRI) data. The purpose of this proposal is to better understand if time-delay processed CVR metrics
are associated with a faster longitudinal increase in SVD pathology and faster cognitive decline. In particular,
we will assess (1) if impaired CVR and elevated CVRDELAY in the cerebral white matter relate a faster increase
in white matter hyperintensities (WMHs) and enlarged perivascular spaces (ePVS) burden, and (2) if impaired
CVR and elevated CVRDELAY in grey matter lobar regions of interest are related to faster longitudinal cognitive
decline in specific cognitive domains. To fulfill the research aims of this F31 application, we will leverage
exceptional resources from the Vanderbilt Memory & Alzheimer’s Center, Vanderbilt Memory & Aging Project,
Vanderbilt University Institute of Imaging Science, Vanderbilt Advanced Computing Center for Research and
Education, and the Vanderbilt Brain Institute. The candidate, Hudson Robb, will carry out the proposed
research with the support of an interdisciplinary mentorship team, including experts in the neurobiology of
Alzheimer’s disease and small vessel disease, geriatric neuropsychology, neuroscience, and brain MRI. The
parallel training plan will provide the candidate with the necessary knowledge and skillset to complete the
proposed research aims and develop into a successful neuroscientist working at the neurobiological
intersection of SVD, AD, and cognitive impairment. Results from this research will offer crucial insight into
associations between a relatively novel biomarker of vascular function and SVD and cognitive impa...

## Key facts

- **NIH application ID:** 10537193
- **Project number:** 1F31AG079640-01
- **Recipient organization:** VANDERBILT UNIVERSITY
- **Principal Investigator:** William Hudson Robb
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $32,031
- **Award type:** 1
- **Project period:** 2022-09-01 → 2025-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10537193

## Citation

> US National Institutes of Health, RePORTER application 10537193, Cerebrovascular neuroimaging markers and abnormal brain aging (1F31AG079640-01). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10537193. Licensed CC0.

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