# Microvascular Disease Burden and Cerebral Small Vessel Disease: Relations to Neurocognition

> **NIH NIH R01** · CEDARS-SINAI MEDICAL CENTER · 2022 · $438,723

## Abstract

PROJECT SUMMARY/ABSTRACT
Small vessel disease of the brain and the heart have far-reaching clinical implications and billions of dollars in
annual healthcare costs. From a pathophysiological perspective, both organs share common risk factors (e.g.,
hypertension, diabetes, dyslipidemia, aging, etc.) and are affected to a similar extent by systemic inflammation,
ischemia due to atherosclerosis, vasospasm, micro-emboli and neuroendocrine dysfunction. Additionally, there
is increasing awareness that sex differences develop and modify the interaction between the heart and the
brain. Surprisingly, despite such compelling similarities between CMD and CSVD pathogenesis, divergent
diagnostic and therapeutic approaches currently exist. A recent review summarizing parallels between CMD
and CSVD using magnetic resonance imaging (MRI) notably did not include investigation where both
conditions were simultaneously studied. In our hands, CMD is indeed associated with increased risk of stroke,
and we have preliminarily linked retinal microvascular structure and peripheral vascular function to CMD,
suggesting concomitant research may be useful. Given that CMD therapeutic investigation is now underway,
concurrent study with CSVD may provide novel treatment targets. Our parent NHLBI-funded Women's
Ischemia Syndrome Evaluation (WISE) Pre-HFpEF (1R01HL146158) is testing the hypothesis that CMD-
related ischemia is a precursor of features of HFpEF in 180 women and men. The WISE subjects are deeply
phenotyped, undergo repeated testing, and are typically followed for at least 10 years. An additional parent
NIA-funded MAE-WEST SCORE Project 2 (1U54AG065141) adds retinal photography, peripheral
microvascular reactivity, and cognitive function to the NHLBI WISE cohort to evaluate the hypothesis that
microvascular disease burden is related across major organ systems. We propose the following Aims for an
Alzheimer's-Focused Administrative Supplements for NIH Grant Not Focused on Alzheimer's. In 100
participants enrolled in WISE PreHFpEF with retinal imaging, peripheral vascular measurements and cognitive
testing: Aim 1: Test the hypothesis that CSVD is directly related to microvascular disease burden. We will
investigate relations between measures of CMD, retinal microvascular structure, and peripheral
microvascular reactivity, with MRI markers of CSVD, including cerebral perfusion, cerebral white matter
volume, cerebral white matter hyperintensities volume, and functional connectivity. Aim 2: Test the hypothesis
that CMD and CSVD similarly contribute to cognitive function. We will comparatively relate MRI measures of
CMD and CSVD to the measures of cognitive function. Our study will: 1) establish an at-risk cohort to allow
future prospective study of heart, brain and cognitive trajectories; 2) evaluate a variety of brain MRI markers to
identify those of potential use in future prospective work; and 3) provide a platform for future clinical trial
planning. Specifically, shou...

## Key facts

- **NIH application ID:** 10499974
- **Project number:** 3R01HL146158-04S1
- **Recipient organization:** CEDARS-SINAI MEDICAL CENTER
- **Principal Investigator:** Cathleen Noel Bairey Merz
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $438,723
- **Award type:** 3
- **Project period:** 2019-05-01 → 2024-02-29

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10499974

## Citation

> US National Institutes of Health, RePORTER application 10499974, Microvascular Disease Burden and Cerebral Small Vessel Disease: Relations to Neurocognition (3R01HL146158-04S1). Retrieved via AI Analytics 2026-05-28 from https://api.ai-analytics.org/grant/nih/10499974. Licensed CC0.

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