# Enlarged Perivascular Spaces as Markers of Vascular and Alzheimer pathology: predictors, pathophysiology and clinical consequences

> **NIH NIH R01** · BOSTON UNIVERSITY MEDICAL CAMPUS · 2021 · $613,748

## Abstract

Dementia is a major public health problem affecting 4.7 million individuals with estimated annual costs of $200
billion. There is a pressing need to understand its pathophysiology, identify treatment targets and develop
preventive strategies. Enlarged perivascular spaces (ePVS) are an emerging MRI marker thought to reflect
dysfunction of the newly discovered glymphatic system crucial to removal of beta-amyloid (Aβ) load in
individuals at risk for Alzheimer disease (AD) and cerebral amyloid angiopathy (CAA). ePVS also appear to
reflect small vessel vascular brain injury that may be synergistic with the Alzheimer neurodegenerative
process. In the Framingham Heart Study (FHS), we are uniquely positioned to study ePVS as a measure of
glymphatic dysfunction, as well as a marker of CSVD and risk of stroke and dementia in healthy adults.
Similarly, we are uniquely situated to explore novel aspects in their pathophysiology that may identify
preventive and treatment strategies for stroke and dementia. We will create a new dataset of ePVS on over
7,000 brain MRI scans already available in the FHS Cohorts. FHS participants represent the entire life span
(ages 19 – 101 years), have been thoroughly characterized and followed over decades for incident AD, all
dementia, and stroke. We propose to study ePVS to determine their age and sex-specific prevalence and
relation to vascular risk factors; novel predictors focused on the relation to circulating biomarkers of systemic
and vascular inflammation that may reveal insight into potential treatment targets. We will study the ePVS role
as mediator in the novel association between sleep dysfunction and brain amyloid burden (assessed in PET
imaging and neuropathology) that may also represent a treatment target for prevention of dementia. Finally, in
the last of our primary aims we will evaluate the adverse clinical consequences of high burden of ePVS in
healthy community dwelling individuals. In an exploratory aim we propose to assess the brain MRI correlates,
traditional and novel measures of brain integrity and aging (DTI, including probabilistic tractography, gray
matter volumes, and functional connectivity). Our hypotheses are: (1) the prevalence of ePVS will increase
with age, will differ in women and men, and increase with exposure to traditional vascular risk factors; (2)
higher levels of circulating biomarkers of inflammation will relate to ePVS severity; (3) ePVS mediate at least in
part the association between sleep dysfunction and amyloid burden; (4) higher burden of ePVS will relate to
higher risk of AD, all dementia, stroke, impaired cognition, physical function and depression symptomatology.
Epidemiological characterization of ePVS may help identify individuals at high risk for targeted preventive
strategies, identify novel mechanisms leading to AD and may lead to identification of novel treatment targets
for AD, other dementias and stroke.

## Key facts

- **NIH application ID:** 10143154
- **Project number:** 5R01AG059725-03
- **Recipient organization:** BOSTON UNIVERSITY MEDICAL CAMPUS
- **Principal Investigator:** Jose Rafael Romero
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $613,748
- **Award type:** 5
- **Project period:** 2019-08-01 → 2024-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10143154

## Citation

> US National Institutes of Health, RePORTER application 10143154, Enlarged Perivascular Spaces as Markers of Vascular and Alzheimer pathology: predictors, pathophysiology and clinical consequences (5R01AG059725-03). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10143154. Licensed CC0.

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