# Non-Atherosclerotic Brain Arterial Remodeling and Associated Vascular Dementia Risk

> **NIH NIH R21** · JOHNS HOPKINS UNIVERSITY · 2021 · $458,275

## Abstract

Non-Atherosclerotic Brain Arterial Remodeling and Associated Vascular Dementia Risk
Non-atherosclerotic brain arterial remodeling (NABAR) of the large intracranial arteries has recently emerged
as a determinant of poor cognitive outcomes. Vascular aging is associated with elastin fragmentation and
collagen deposition, and may present as either outward or tortuous remodeling, both of which may occur in the
absence of atherosclerosis. In cross-sectional studies, non-atherosclerotic outward remodeling of the cerebral
vasculature has been reported in association with diminished cognitive function. However, the extent to which
brain arterial remodeling is permanent vs. reversible, or whether it progresses with age in older individuals is
unknown. Mechanistic studies suggest that arterial wall thickness is regulated by intraluminal pressure and wall
tension, and that arterial lumen diameter is regulated by blood flow and shear stress. Tortuous elongation has
also been associated with mechanical factors, including blood flow, blood pressure, axial tension and wall
changes. It is thus plausible that brain arterial remodeling may be dynamic rather than static, even in
individuals of advanced age. We propose to examine prevalence and rate of change in NABAR, quantified by
luminal diameters and degree of tortuosity, in older individuals from the general population who were imaged
by brain MRI at 2 time points. We aim to determine whether vascular risk factors at midlife and their trajectories
since midlife associate with NABAR in late life. We will also identify putative factors which may be associated
with an accelerated 5-year progression of remodeling in late life. As secondary aims, we will examine the
prospective relationship between NABAR and 5-year neurocognitive outcomes (change in cognition and
incidence of vascular mild cognitive impairment or vascular dementia), as well as the correlation between 5-
year change in NABAR and 5-year change in cognition. We will be uniquely positioned to carry out this project
in the Atherosclerosis Risk in Communities study, which has collected clinical data from cohort members over
the past 30 years, including multiple assessments by brain MRI and cognitive testing. We will quantify NABAR
(dilation and tortuosity) in the basilar artery, middle cerebral arteries, and internal carotid arteries, using
existing MRI data (TOF MRA and 3D vessel wall imaging) from ARIC study visit 5 (2011-2013, completed) and
visit 6/7 (2016-2019).

## Key facts

- **NIH application ID:** 10194703
- **Project number:** 1R21AG072244-01
- **Recipient organization:** JOHNS HOPKINS UNIVERSITY
- **Principal Investigator:** MELISSA C CAUGHEY
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $458,275
- **Award type:** 1
- **Project period:** 2021-05-01 → 2024-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10194703

## Citation

> US National Institutes of Health, RePORTER application 10194703, Non-Atherosclerotic Brain Arterial Remodeling and Associated Vascular Dementia Risk (1R21AG072244-01). Retrieved via AI Analytics 2026-05-29 from https://api.ai-analytics.org/grant/nih/10194703. Licensed CC0.

---

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