# Genetic Contribution to Brain Arterial Dilatation and its Role in Cognition and dementia

> **NIH NIH R01** · COLUMBIA UNIVERSITY HEALTH SCIENCES · 2020 · $90,459

## Abstract

PROJECT SUMMARY/ABSTRACT:
Alzheimer disease is expected to affect over 13 million Americans by 2050. There is ample evidence that
relates vascular disease to Alzheimer disease, and the vascular contributions to cognitive decline and
dementia are a national research priority. Data from our group and others have demonstrated that brain large
artery disease is an important determinant of cerebrovascular health and, consequently, of cognitive function.
For example, narrowing of the brain arteries due to atherosclerosis has been associated with an increased risk
of Alzheimer disease and vascular dementia. The field has long focused on atherosclerosis and stenosis as
the sole contributors to cerebrovascular health, however. We believe that brain arterial dilatation may also be
deleterious to brain health. Consequently, we propose a change in the paradigm of brain large artery disease
that goes beyond atherosclerosis and/or stenosis, and incorporates brain arterial dilatation as a distinct
pathological phenotype. We postulated that, as with many anthropomorphic measurements, the diameters of
brain arteries are normally distributed and that the extremes of this distribution are pathological. We have
confirmed this hypothesis. We reported that among individuals with the largest or the smallest brain arterial
diameters, the risk of vascular event is higher. The increased risk of vascular events among these individuals
with extreme cerebral phenotypes is partially explained by the co-existence of systemic but not necessarily
cerebral atherosclerosis. We have also demonstrated that non-atherosclerotic brain arterial aging relates to
Alzheimer pathology independent of atherosclerosis and brain infarcts. We have gathered preliminary data
showing that brain arterial diameters are associated non-linearly with cognition, so that individuals with
narrowed or dilated brain arteries have poorer cognitive performance compared with those with average
arterial diameters. Because brain arterial dilatation is understudied, it will be the focus of our proposal. Brain
arterial dilatation may occur among patients with genetic syndromes predisposing to weaker connective tissue,
but it is unclear whether genetic predisposing factors exist in the general population. It is plausible that the
mechanical effects of brain arterial dilatation over the distal arteriolar and capillary flow may disrupt cerebral
autoregulation, and explain the relationship with parenchymal functions such as cognition. It remains unclear
whether these genetic factors are effect modifiers or direct contributors to cognition. This proposal aims to
address these uncertainties. In Aim 1, we will define genetic loci that relate to brain arterial dilatation in >5,000
participants of four well-characterized, population-based studies with longitudinal follow-up who also have
neuroimaging and cognitive assessments. In Aim 2, we will establish the hemodynamic consequences of brain
arterial dilatation by relating ...

## Key facts

- **NIH application ID:** 10083526
- **Project number:** 3R01AG057709-03S2
- **Recipient organization:** COLUMBIA UNIVERSITY HEALTH SCIENCES
- **Principal Investigator:** Jose Gutierrez
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $90,459
- **Award type:** 3
- **Project period:** 2018-08-15 → 2023-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10083526

## Citation

> US National Institutes of Health, RePORTER application 10083526, Genetic Contribution to Brain Arterial Dilatation and its Role in Cognition and dementia (3R01AG057709-03S2). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10083526. Licensed CC0.

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