Cerebral White Matter Hyperintensity in African Americans and European Americans with Type 2 Diabetes

doi:10.1016/j.jstrokecerebrovasdis.2012.03.019

Journal of Stroke and Cerebrovascular Diseases

Volume 22, Issue 7, October 2013, Pages e46-e52

https://doi.org/10.1016/j.jstrokecerebrovasdis.2012.03.019 Get rights and content

Previous studies involving inner city populations detected higher cerebral white matter hyperintensity (WMH) scores in African Americans (AAs) compared with European Americans (EAs). This finding might be attributable to the higher prevalence of cardiovascular disease (CVD) risk factors and poorer access to healthcare in AAs. Despite racial differences in CVD risk factor profiles, AAs have paradoxically lower levels of subclinical CVD. We hypothesized that AAs with diabetes and good access to healthcare would have comparable or lower levels of WMH as EAs. Racial differences in the distribution of WMH were analyzed in 46 AAs and 156 EAs with type 2 diabetes enrolled in the Diabetes Heart Study (DHS)-Mind, and replicated in a sample of 113 AAs and 61 EAs patients who had clinically indicated cerebral magnetic resonance imaging. Wilcoxon 2-sample tests and linear models were used to compare the distribution of WMH in AAs and EAs and to test for association between WMH and race. The unadjusted mean WMH score from the Diabetes Heart Study–Mind was 1.9 in AAs and 2.3 in EAs (P = .3244). Among those with clinically indicated magnetic resonance imaging, the mean WMH score was 2.9 in AAs and 3.9 in EAs (P = .0503). Adjustment for age and sex produced no statistically significant differences in WMH score between AAs and EAs. These independent datasets reveal comparable WMH scores in AAs and EAs, suggesting that disparities in access to healthcare and environmental exposures likely underlie the previously reported excess burden of WMH in AAs.

Section snippets

Study Populations

For analyses in DHS-Mind (including AA-DHS-Mind participants), a subsample was selected comprising all 46 unrelated AA participants recruited to date and 156 age- and sex-matched unrelated EAs with similar demographic and clinical characteristics as the AA participants. Recruitment and ascertainment of DHS participants has been described previously. In brief, the DHS recruited siblings concordant for T2D without evidence of advanced renal insufficiency through internal medicine clinics and

Results

The distribution of WMH was compared in the 46 AAs and 156 matched EAs in the DHS-Mind series. As in the full AA-DHS sample,²¹ the AAs had a similar mean duration of T2D as the EAs despite being on average 6 years younger than the EAs (Table 1). Baseline data revealed that AAs in the DHS-Mind had higher mean diastolic blood pressure (73.0 vs 68.6 mm Hg) and slightly lower mean body mass index (33.7 vs 36.0 kg/m²). There were no statistically significant differences between the AAs and EAs in

Discussion

Our analysis of independent datasets including patients with T2D residing in North Carolina revealed equal or slightly lower levels of WMH in AAs compared with EAs. These findings stand in stark contrast to those of 2 previous reports. The Chicago Health and Aging Project (CHAP) and Washington Heights–Inwood Columbia Aging Project (WHICAP) reported equal or greater WMH scores in AAs relative to EAs, as well as significantly higher burdens of conventional CBVD risk factors in AAs. CHAP assessed

Acknowledgments

We thank all of the participants in this study, as well as Cassandra Bethea, RN, principal recruiter for the DHS-Mind study, and Sally Mauney, Carol Thomas, and Joni Hanna, study coordinators for the DHS-Mind study.

Author Contributions: JD, KMS, JAM, and BIF conceptualized and designed the study. JD conducted the statistical analyses, with input from CH, KMS, JAM, and BIF. YG wrote the application for searching the hospital database to identify the sample of patients with clinically indicated

References (30)

C. Cooper et al.
A systematic review and meta-analysis of ethnic differences in use of dementia treatment, care, and research
Am J Geriatr Psychiatry
(2010)
D.H. Salat et al.
Age-associated alterations in cortical gray and white matter signal intensity and gray to white matter contrast
Neuroimage
(2009)
B.A. Young et al.
Racial and ethnic differences in incident myocardial infarction in end-stage renal disease patients: The USRDS
Kidney Int
(2006)
W.R. Brown et al.
Apoptosis in leukoaraiosis
AJNR Am J Neuroradiol
(2000)
A.J. Thomas et al.
Ischemic basis for deep white matter hyperintensities in major depression: A neuropathological study
Arch Gen Psychiatry
(2002)
L. Pantoni et al.
Pathogenesis of leukoaraiosis: A review
Stroke
(1997)
A.D. Murray et al.
Brain white matter hyperintensities: Relative importance of vascular risk factors in nondemented elderly people
Radiology
(2005)
S. Debette et al.
The clinical importance of white matter hyperintensities on brain magnetic resonance imaging: Systematic review and meta-analysis
BMJ
(2010)
N.D. Prins et al.
Cerebral white matter lesions and the risk of dementia
Arch Neurol
(2004)
L.H. Kuller et al.
White matter hyperintensity on cranial magnetic resonance imaging: A predictor of stroke
Stroke
(2004)

S. Debette et al.

Association of MRI markers of vascular brain injury with incident stroke, mild cognitive impairment, dementia, and mortality: The Framingham Offspring Study

Stroke

(2010)

N.T. Aggarwal et al.

The association of magnetic resonance imaging measures with cognitive function in a biracial population sample

Arch Neurol

(2010)

A.M. Brickman et al.

Brain morphology in older African Americans, Caribbean Hispanics, and whites from northern Manhattan

Arch Neurol

(2008)

K. Stavitsky et al.

White matter hyperintensity and cognitive functioning in the racial and ethnic minority cohort of the Framingham Heart Study

Neuroepidemiology

(2010)

C.K. Francis

Hypertension, cardiac disease, and compliance in minority patients

Am J Med

(1991)

Cited by (17)

White matter hyperintensities in diverse populations: A systematic review of literature in the United States
2024, Cerebral Circulation - Cognition and Behavior
As the United States’ (US) elderly population becomes increasingly diverse, it is imperative that research studies address cognitive health in diverse populations of older Americans. White Matter Hyperintensities (WMH) are useful imaging findings that can be studied in elderly individuals and have been linked to an increased risk of neurological conditions, such as stroke, cognitive impairment, and dementia. We performed a systematic review of literature using PubMed sources to compile all the studies that investigated the prevalence of ethnic and racial differences of WMH burden amongst diverse groups in the US. We identified 23 unique articles that utilized 16 distinct cohorts of which 94 % were prospective, longitudinal studies that included community-based and family-based populations. The overall results were heterogenous in all aspects of data collection and analysis, limiting our ability to run meta-analyses and draw definitive conclusions. General observations suggest increased vascular risk on African American populations, contributing to greater WMH burden in that population. Overall, the findings of this study indicate a need for a standardized approach to investigating WMH in efforts to measure its clinical impact on diverse populations.
Racial differences in white matter hyperintensity burden in older adults
2023, Neurobiology of Aging
Citation Excerpt :
When examining WMHs in a racially diverse cohort, results have been conflicting as to whether racial differences in WMH burden exist. For example, some studies report that there are no significant differences in WMH burden because of racial group (when comparing African American/Black individuals [hereafter referred to as Black{s}] to European American/Caucasian/White individuals [hereafter referred to as White{s}]) (Amariglio et al., 2020; Divers et al., 2013). Conversely, other studies have reported increased WMH burden in Blacks compared to Whites (Brickman et al., 2008; Zahodne et al., 2015).
White matter hyperintensities (WMHs) may be one of the earliest pathological changes in aging. Race differences in WMH burden has been conflicting. This study examined if race influences WMHs and whether these differences are influenced by vascular risk factors. Alzheimer's Disease Neuroimaging Initiative participants were included if they had a baseline MRI, diagnosis, and WMH measurements. Ninety-one Blacks and 1937 Whites were included. Using bootstrap re-sampling, 91 Whites were randomly sampled and matched to Blacks based on age, sex, education, and diagnosis 1000 times. Linear models examined the influence of race on baseline WMHs, and change of WMHs over time, with and without vascular factors. Vascular risk factors had higher prevalence in Blacks than Whites. When not including vascular factors, Blacks had greater frontal, parietal, deep, and total WMH burden compared to Whites. There were no race differences in longitudinal progression of WMH accumulation. After controlling for vascular factors, only overall longitudinal parietal WMH group differences remained significant, suggesting that vascular factors contribute to racial group differences observed in WMHs.
Construction and validation of a cerebral white matter hyperintensity probability map of older Koreans
2021, NeuroImage: Clinical
Citation Excerpt :
First, the differences between age groups may not necessarily indicate the age-associated changes because this study employed a cross-sectional design. Second, our WMP may not be directly applicable to the population of different ethnicities like Caucasians and/or living in different geographic regions because brain shape is different between ethnic groups (Lee et al., 2016) and the risk of WMH is also different between ethnic groups and/or geographic regions with different lifestyles and environments (Divers et al., 2013; Gow et al., 2012). Third, although we tried to compensate for differences in resolution of the images by normalizing them to a common template, pooling MR images from two different scanners and protocols might influence the accuracy for the measurement (Schnack et al., 2004).
Although two white matter hyperintensity (WMH) probability maps of healthy older adults already exist, they have several limitations in representing the distribution of WMH in healthy older adults, especially Asian older adults. We constructed and validated a WMH probability map (WPM) of healthy older Koreans and examined the age-associated differences of WMH.
We constructed WPM using development dataset that consisted of high-resolution 3D fluid-attenuated inversion recovery images of 5 age groups (60–64 years, 65–69 years, 70–74 years, 75–79 years, and 80+ years). Each age group included 30 age-matched men and women each. We tested the validity of the WPM by comparing WMH ages estimated by the WPM and the chronological ages of 30 healthy controls, 30 hypertension patients, and 30 S patients.
Older age groups showed a higher volume of WMH in both hemispheres (p < 0.001). About 90% of the WMH were periventricular in all age groups. With advancing age, the peak of the distance histogram from the ventricular wall of the periventricular WMH shifted away from the ventricular wall, while that of deep WMH shifted toward the ventricular wall. The estimated WMH ages were comparable to the chronological ages in the healthy controls, while being higher than the chronological ages in hypertension and stroke patients.
This WPM may serve as a standard atlas in research on WMH of older adults, especially Asians.
Relationships between cerebral structure and cognitive function in African Americans with type 2 diabetes
2018, Journal of Diabetes and its Complications
Citation Excerpt :
In multi-ethnic cohorts, type 2 diabetes is associated with brain atrophy and WML burden, which are in turn associated with poorer cognitive performance.21, 22 We previously reported in the DHS MIND study that the extent of white matter disease is similar between African Americans and European Americans with type 2 diabetes.43 WML burden was associated with poorer cognitive performance in European American participants (DSC, RAVLT and semantic fluency) and with DSC and Stroop interference in African Americans.21, 22
Relationships between cognitive function and brain structure remain poorly defined in African Americans with type 2 diabetes.
Cognitive testing and cerebral magnetic resonance imaging in African Americans from the Diabetes Heart Study Memory IN Diabetes (n = 480) and Action to Control Cardiovascular Risk in Diabetes MIND (n = 104) studies were examined for associations. Cerebral gray matter volume (GMV), white matter volume (WMV) and white matter lesion volume (WMLV) and cognitive performance (Mini-mental State Exam [MMSE and 3MSE], Digit Symbol Coding (DSC), Stroop test, and Rey Auditory Verbal Learning Test) were recorded. Multivariable models adjusted for age, sex, BMI, scanner, intracranial volume, education, diabetes duration, HbA1c, LDL-cholesterol, smoking, hypertension and cardiovascular disease assessed associations between cognitive tests and brain volumes by study and meta-analysis.
Mean(SD) participant age was 60.1(7.9) years, diabetes duration 12.1(7.7) years, and HbA1c 8.3(1.7)%. In the fully-adjusted meta-analysis, lower GMV associated with poorer global performance on MMSE/3MSE ( $\hat{β}$  = 7.1 × 10⁻³, SE 2.4 × 10⁻³, p = 3.6 × 10⁻³), higher WMLV associated with poorer performance on DSC ( $\hat{β}$  = −3 × 10⁻², SE 6.4 × 10⁻³, p = 5.2 × 10⁻⁵) and higher WMV associated with poorer MMSE/3MSE performance ( $\hat{β}$  = −7.1 × 10⁻³, SE = 2.4 × 10⁻³, p = 3.6 × 10⁻³).
In African Americans with diabetes, smaller GMV and increased WMLV associated with poorer performance on tests of global cognitive and executive function. These data suggest that WML burden and gray matter atrophy associate with cognitive performance independent of diabetes-related factors in this population.
Racial Difference in Cerebral Microbleed Burden Among a Patient Population in the Mid-South United States
2018, Journal of Stroke and Cerebrovascular Diseases
Citation Excerpt :
In our study, although African-Americans had a higher rate of large confluent white matter lesions, we did not observe a significant racial difference in the severity of white matter disease. This observation is consistent with our previous observation among African-Americans and White stroke patients20 as well as results from Wake Forest datasets containing black and white patients with type 2 diabetes.21 However, Nyquist et al found that African-American race is an independent risk factor for severe white matter lesions in a population enriched for vascular risk factors.22
Although intracerebral hemorrhage (ICH) is more common among African-Americans, data on the burden of cerebral microbleeds (CMBs) among different races is limited. The purpose of this study is to compare the number, associated factors, and topography of CMBs between African-American and Caucasian populations in the Mid-South United States.
Using natural language processing, we extracted all brain MRIs performed during a 2-year period (2012-2013) when the report indicated the presence of CMB. All the extracted MRI studies were evaluated for number and location of CMBs, prior stroke, and deep white matter lesion. Negative binomial regression was used to model for the overdispersed count data.
A total 167 patients (mean age was 63 ± 15 years, 49% men, 77% African-American, median CMB count: 8) with 1 or more CMBs on their brain MRI were included in this study. There was no significant difference between the 2 groups in terms of CMB locations (P = .086), but there was a significant difference between African-American and Caucasian patients in terms of number of CMBs (16.5 ± 18 versus 6.5 ± 5.5, P < .001). The prevalence of multiple CMBs (CMBs ≥ 5) was similar among African-Americans and Caucasians (72% versus 55%, P = .062). After adjusting for potential confounders, the African-American race was not independently associated with a higher CMB burden (P = .073).
African-American race was not independently associated with a higher rate of CMB burden when compared to Caucasians after adjusting for potential confounders. We also did not observe a significant racial difference regarding the location and prevalence of multiple CMBs (CMBs ≥ 5).
Racial Difference in Cerebral Microbleed Burden among Ischemic Stroke Patients
2017, Journal of Stroke and Cerebrovascular Diseases
Citation Excerpt :
Although African American stroke patients had a higher rate of large confluent white matter lesions in our study, we did not observe a significant racial difference in the severity of DWML. Analyses of independent Wake Forest datasets containing patients with type 2 diabetes also did not show a higher rate of white matter hyperintensity among African Americans.45 However, Nyquist et al found that African American race is an independent risk factor for extreme DWML volume in a population enriched for vascular risk factors.46
Data on the epidemiology of cerebral microbleeds (CMBs) among patients with ischemic stroke are limited. This study compared the number, associated factors, and topography of CMBs between African American and Caucasian ischemic stroke patients in the Mid-South United States.
We evaluated consecutive ischemic stroke patients admitted to our tertiary stroke center, University of Tennessee Health Science Center, Memphis, Tennessee, in a two-year period. We analyzed T2*-weighted magnetic resonance images for the number, location, and topography of CMBs, as well as patients' demographic and clinical information.
Among 760 ischemic stroke patients who were included (mean age was 62.1 ± 13.9 years, 51.4% men), 450 (59.2%) were African American. In comparison with Caucasians, African Americans were about five years younger (P = .000) and had a higher rate of hypertension (80.9% vs. 74.5%, P = .036). Similarly, African Americans had a higher prevalence of diabetes mellitus (P = .001). There was no significant difference between African-Americans and Caucasians in terms of CMBs presence and location. African Americans had a higher number of CMBs in comparison with Caucasians, but the difference was not significant. African Americans were more likely to have CMBs ≥5 (P = .047). Although African American stroke patients had a higher rate of large confluent white matter lesions, there was no significant racial difference regarding the rate and severity of deep white matter lesions.
We did not observe any differences between African American and Caucasian patients with ischemic stroke patients regarding the presence, number, and location of CMBs. However, our results suggested that the prevalence of multiple CMBs (CMBs ≥5) might be higher among African American stroke patients.

View all citing articles on Scopus

: Supported in part by the General Clinical Research Center of the Wake Forest University School of Medicine grant MO1 RR07122, National Institute of Diabetes and Digestive and Kidney Diseases grant RO1 DK071891 (to BIF), National Heart, Lung, and Blood Institute grant RO1 HL67348 (to DWB), National Institute of Diabetes and Digestive and Kidney Diseases grant F32 DK083214(to CH), and National Institute of Neurological Disorders and Stroke grant RO1 NS075107 (to JD, JAM, and BIF).

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Review ArticleCerebral White Matter Hyperintensity in African Americans and European Americans with Type 2 Diabetes

Section snippets

Study Populations

Results

Discussion

Acknowledgments

Am J Geriatr Psychiatry

Neuroimage

Kidney Int

Apoptosis in leukoaraiosis

AJNR Am J Neuroradiol

Ischemic basis for deep white matter hyperintensities in major depression: A neuropathological study

Arch Gen Psychiatry

Pathogenesis of leukoaraiosis: A review

Stroke

Brain white matter hyperintensities: Relative importance of vascular risk factors in nondemented elderly people

Radiology

The clinical importance of white matter hyperintensities on brain magnetic resonance imaging: Systematic review and meta-analysis

BMJ

Cerebral white matter lesions and the risk of dementia

Arch Neurol

White matter hyperintensity on cranial magnetic resonance imaging: A predictor of stroke

Stroke

Association of MRI markers of vascular brain injury with incident stroke, mild cognitive impairment, dementia, and mortality: The Framingham Offspring Study

Stroke

The association of magnetic resonance imaging measures with cognitive function in a biracial population sample

Arch Neurol

Brain morphology in older African Americans, Caribbean Hispanics, and whites from northern Manhattan

Arch Neurol

White matter hyperintensity and cognitive functioning in the racial and ethnic minority cohort of the Framingham Heart Study

Neuroepidemiology

Hypertension, cardiac disease, and compliance in minority patients

Am J Med

Review Article
Cerebral White Matter Hyperintensity in African Americans and European Americans with Type 2 Diabetes