Cerebral small vessel disease (CSVD) is a common, progressive condition of aging, and a leading contributor to age-related disability due to stroke, cognitive decline, late-life onset depression and gait deterioration. In most cases the underlying vessel pathology can be classified as one of the two most common subtypes, arteriolosclerosis (AS) and cerebral amyloid angiopathy (CAA). Although classically recognized as white matter changes on MRI, CSVD frequently comes to clinical attention for the first time when a patient presents with intracerebral hemorrhage (ICH). Discovering the biological underpinnings of CSVD is a vital next step toward development of effective preventative strategies. Because their CSVD is uniformly severe, ICH survivors are ideal subjects in which to study CSVD and also form the group most likely to benefit from novel therapies. The proposed studies are motivated by the striking observation that ICH disproportionately affects African- American (AA) and Hispanic-American (HA) populations. Our preliminary analyses demonstrate that these differences extend to post-ICH risk for recurrent ICH, cognitive decline and late-life depression and that blood pressure (BP) may play a fundamental role in these differences. Our revised proposal, best titled Longitudinal Follow-up of ICH Survivors in ERICH, will systematically determine whether 1) AA and HA are predisposed to CSVD of all types, 2) are predisposed solely to increased risk of AS, or 3) have no inherent predisposition but, through the effects of BP suffer more severe CSVD. To test the central hypothesis that discovering the mechanisms for this health disparity ICH will yield biological insights for CSVD, advance the search for treatments and have impact at the bedside, we propose to leverage the soon- to-conclude Ethnic/Racial Variations of ICH (ERICH) study to perform longitudinal follow-up of a cohort of 900 ICH survivors (300 each of AA, HA, and NHW), recruited in the last two years of ERICH, who have had neuroimaging, genetic, epidemiologic, and socio-ethnic variables ascertained at time of enrollment. Subjects will be followed by telephone every 6 months according to established and validated protocols.

Public Health Relevance

Cerebral small vessel disease (CSVD) is a common, progressive condition of aging, and a leading contributor to age-related disability due to stroke, cognitive decline, gait deterioration, and late-life depression. The most severe and acute manifestation of CSVD is intracerebral hemorrhage (ICH), which is frequently the sentinel event that brings a patient's CSVD to clinical attention for the first time. ICH and CSVD affect African-American and Hispanic individuals differently compared to non-Hispanic Whites. The proposed study seeks to better characterize the mechanisms for this health disparity by determining why African-American and Hispanic survivors of ICH are at higher risk of recurrent ICH, cognitive decline and incident depression, all of which are manifestations of progressive CSVD.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Research Project (R01)
Project #
5R01NS093870-03
Application #
9413371
Study Section
Acute Neural Injury and Epilepsy Study Section (ANIE)
Program Officer
Moy, Claudia S
Project Start
2016-02-01
Project End
2021-01-31
Budget Start
2018-02-01
Budget End
2019-01-31
Support Year
3
Fiscal Year
2018
Total Cost
Indirect Cost
Name
Massachusetts General Hospital
Department
Type
DUNS #
073130411
City
Boston
State
MA
Country
United States
Zip Code
02114