# Non-Invasive Imaging Markers to Elicit the Role of Vascular Involvement in Alzheimer’s Disease

> **NIH NIH R01** · UNIVERSITY OF WISCONSIN-MADISON · 2022 · $608,186

## Abstract

ABSTRACT
Alzheimer's disease (AD) is the 6th leading cause of death in the United States and its prevalence continues to
rise. AD has no clinically available curative treatments and findings from active clinical trials testing novel
disease-modifying therapeutics have thus far been disappointing. There is, therefore, a growing urgency to
identify early markers of AD, causative factors leading to dementia, and alternative treatment approaches for
halting the global crisis posed by this debilitating condition. Cardiovascular disease, as well as cerebrovascular
disease (CVD), has a strong link with both mild cognitive impairment and AD dementia; however, the question
of whether CVD modulates underlying pathophysiology of AD has only recently begun receiving attention. To
provide insights into AD relationships, non-invasive Magnetic Resonance Imaging (MRI) is being utilized in
longitudinal studies of AD risk-enriched populations. The present project goes far beyond currently available MRI
techniques which lack sensitivity and specificity to address key vascular hypotheses in AD. MRI methods
commonly employed today such as fluid attenuation and susceptibility imaging only indirectly measure CVD and
cannot inform on the dynamic vascular motion and hemodynamic phenomena that have been indicated in animal
models to affect AD pathology. To address these gaps, the overarching objective of this project is to enable
characterization of cerebrovascular involvement in AD through the development and study integration
of a novel battery of non-invasive, MRI-based measures of cerebrovascular health. Building upon
foundational studies at our institution, this work proposes innovative MRI technology to improve characterization
of CVD in AD, specifically vascular stiffening and its relationship with cerebrovascular flow dynamics. We
propose an ensemble of motion encoded MRI techniques which provide detailed depiction of autoregulatory flow
dynamics and vascular stiffness in both the macro and micro vasculature. In this project, the novel methods will
be technically developed harnessing deep learning from vast prior imaging data, validated with optical imaging,
and characterized in healthy human subjects. We then will obtain key data characterizing cerebrovascular
changes in a study of AD biomarker confirmed subjects with the overall goal of identifying the modifying effect
of vascular disease on the symptom expression of cognitive impairment, AD biomarker accumulation, and
neurodegeneration. Our pilot data suggest subjects with AD have a premature increase in arterial stiffness and
decreased fluctuations in cerebral blood flow. Upon completion, this study will provide insights into which specific
aspects of CVD are primary factors moderating AD interactions. Participants targeted for this study have
extensive existing AD biomarker data and are being followed longitudinally through studies within the Wisconsin
Alzheimer's Disease Research Center. The methodologies wi...

## Key facts

- **NIH application ID:** 10370542
- **Project number:** 1R01AG075788-01
- **Recipient organization:** UNIVERSITY OF WISCONSIN-MADISON
- **Principal Investigator:** Kevin Michael Johnson
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $608,186
- **Award type:** 1
- **Project period:** 2022-02-15 → 2027-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10370542

## Citation

> US National Institutes of Health, RePORTER application 10370542, Non-Invasive Imaging Markers to Elicit the Role of Vascular Involvement in Alzheimer’s Disease (1R01AG075788-01). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10370542. Licensed CC0.

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