# Hemodynamic Mechanisms Linking Aortic Arch Stiffness with Brain Insult in Older Adults

> **NIH NIH R56** · ST. JOSEPH'S HOSPITAL AND MEDICAL CENTER · 2020 · $709,624

## Abstract

Project Summary
Our prior studies suggest that stiffening within the aortic arch (as quantified by aortic arch PWV measured by
MRI) disrupts coupling in the aortic-brain system and consequently increases hemodynamic pulsatility
transmitted to the brain. This project will test the hypothesis that aortic arch stiffness contributes to age-
related brain insults beyond its influence on central pulse pressure by disrupting healthy aorta-brain
system dynamics. We are proposing a systems approach, synergistically combining advanced MRI, fluid
dynamics, and mathematical modeling to understand the basic physics and physiology underlying aorta-brain
hemodynamics. We will test our hypothesis with three specific aims: 1.) Study the mechanisms whereby aortic
arch stiffness impacts the hemodynamics of pulsatile energy transmission to the brain. 2.) Define a systems
model based on the intrinsic frequency (IF) method to describe the healthy aorta-brain system vs. the system
perturbed by aortic arch stiffness. 3). Use mechanistic approaches to understand the impact of disrupted aorta-
brain coupling on brain health and cognitive function. We will use cardiovascular MRI techniques to directly
assess key vascular properties of the system guiding pulsatile wave transmission in the aortic-brain system
including assessment of aortic arch stiffness as well as downstream cerebrovascular resistance and compliance.
We will prospectively study 150 non-demented elders from a deeply phenotyped cohort from a concurrent Brain
Aging Study at Huntington Medical Research Institutes (HMRI). Brain vascular function will be richly
characterized using a combination of imaging techniques and biomarker analysis from bloodwork and
cerebrospinal fluid. Our MRI vascular assessments include automated quantification of white matter
hyperintensity (WMH) volume as well as cerebrovascular reactivity. Brain integrity and risk for neurodegenerative
disease will be assessed with CSF beta-amyloid (Aβ) measurements and a comprehensive neuropsychological
battery which includes indices of global function, memory, and executive function. Arterial function will be
characterized using MRI measures of blood flow in the aorta and carotid artery combined with arterial tonometry
for quantification of the pulsatile hemodynamic energy transmission to the brain, wave reflection analysis, and
evaluation of vascular compliance and resistance. Vascular function data will determine physiologic parameters
for an in-vitro LV-aortic simulator (that includes cerebral vasculature) and computational fluid dynamics models
which will also direct mathematical systems analysis of the aorta-brain system using intrinsic frequency (IF)
method. These studies are designed to enhance understanding of how aortic stiffening leads to
dementia. Our long-term goal is to develop non-invasive, inexpensive, and easy-to-use measures of brain
vascular health that can be used to identify, predict, and quantify risk of vascular brain damage.

## Key facts

- **NIH application ID:** 10231296
- **Project number:** 1R56AG068630-01
- **Recipient organization:** ST. JOSEPH'S HOSPITAL AND MEDICAL CENTER
- **Principal Investigator:** Kevin Sam King
- **Activity code:** R56 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $709,624
- **Award type:** 1
- **Project period:** 2020-09-15 → 2023-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10231296

## Citation

> US National Institutes of Health, RePORTER application 10231296, Hemodynamic Mechanisms Linking Aortic Arch Stiffness with Brain Insult in Older Adults (1R56AG068630-01). Retrieved via AI Analytics 2026-06-01 from https://api.ai-analytics.org/grant/nih/10231296. Licensed CC0.

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