White matter hyperintensities (WMH) are associated with intracranial atherosclerosis rather than extracranial atherosclerosis

doi:10.1016/j.archger.2010.07.008

Archives of Gerontology and Geriatrics

Volume 53, Issue 2, September–October 2011, Pages e129-e132

https://doi.org/10.1016/j.archger.2010.07.008 Get rights and content

Abstract

There is increasing evidence for an association between WMH and large-artery atherosclerosis. We evaluated 268 patients with acute ischemic stroke to assess the relationship between intracranial (IC) atherosclerosis and WMH. The patients were classified into three groups according to the location of the stenosis; IC, extracranial (EC), and non-stenosis (NS) group. WMH were rated using the semiquantitative method of Scheltens and coworkers. The IC group had significantly more WMH score in comparison with the other groups after controlling age. The linear regression analysis showed that age was the factor most strongly associated with the total score of WMH; and the location of stenosis was positively related to WMH, especially in deep white matter. Our data show that IC stenosis is associated with WMH, indicating that IC stenosis, rather than EC stenosis, is likely to cause white matter lesions. These findings raise the possibility that occlusion of penetrating arteries, embolism to border-zone areas and a hemodynamic mechanism associated with IC stenosis leads to the formation of white matter lesions.

Introduction

WMH are ill-defined patchy or confluent periventricular and subcortical lesions of high signal intensity on T2-weighted magnetic resonance images (MRI). WMH are frequently observed in individuals with advanced age, hypertension, prior ischemic stroke and other cerebrovascular risk factors (Räihä et al., 1993, Jørgensen et al., 1995, Hénon et al., 1996, Leys et al., 1999, Wiszniewska et al., 2000, Kalaria and Erkinjuntti, 2006).

WMH are more common in patients with lacunar infarcts than in those with non-lacunar strokes in the literatures (Hijdra et al., 1990, Leys et al., 1999). Pathologically, WMH includes not only demyelination and gliosis, but also lipohyalinosis and fibrinoid necrosis, as seen in lacunar pathology (Fazekas et al., 1993, O'Sullivan, 2008). Thus, the association between lacunar strokes and WMH seems well-documented.

However, there is increasing evidence for a close relationship between large-artery atherosclerosis and WMH. White matter lesions may have a graded correlation with intima media thickness and number of carotid plaques (Bots et al., 1993, De Leeuw et al., 2000), and some studies have demonstrated an association between WMH and unstable carotid plaques (Altaf et al., 2006, Altaf et al., 2008). In addition, we found that patients with large-artery atherosclerosis had the highest incidence of leukoaraiosis in the Korean stroke population, which may be attributed to the fact that Asian populations have a higher predilection for IC diseases (Lee et al., 2008).

Nevertheless, there is little information concerning the role of IC atherosclerosis in WMH available in the literature. The relevance of IC atherosclerosis to WMH may be important due to the dominance of IC occlusive disease in Asian populations (Feldmann et al., 1990, Huang et al., 1997). Therefore, we sought to evaluate the relationship between the location of arterial stenosis and WMH using a semiquantitative rating method.

Section snippets

Patients

We prospectively studied 357 consecutive patients with acute ischemic stroke or transient ischemic attack who were admitted to the Department of Neurology at Seoul St. Mary's Hospital between June 2007 and June 2008. Detailed clinical evaluations, including medical history, laboratory tests, brain MRI, contrast-enhanced MR angiography (MRA), electrocardiography and 24-h Holter monitoring, were performed.

Of 357 patients initially studied, a total of 309 patients were included for the analysis of

Results

The mean age of the 268 patients finally enrolled (152 men and 116 women) was 67.0 ± 12.4 years. The female patients were older than the male patients (70.3 ± 13.4 and 64.6 ± 11.1 years, respectively; p < 0.001 by independent t-test). Table 1 illustrates demographic features and risk factors of patients included. There were significant differences between the groups for age, dyslipidemia, current smoking, HD and alcohol history.

Significantly high WMH score was found in the older patients (p < 0.001). The

Discussion

In this study, age was the most powerful independent variable for WMH. This result is in agreement with the findings of previous studies (Räihä et al., 1993, Jørgensen et al., 1995, Hénon et al., 1996, Leys et al., 1999, Wiszniewska et al., 2000, Kalaria and Erkinjuntti, 2006). Notably, there was an inverse correlation between atrial fibrillation and WMH. This finding is consistent with that of a previous study (Jørgensen et al., 1995), and showed that, among stroke patients, those with atrial

Conflict of interest statement

None.

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Atherosclerotic plaque characteristics in extracranial carotid artery may indicate closer association with white matter hyperintensities than intracranial arteries: A CARE-II study
2024, European Journal of Radiology
This study aimed to investigate the associations of atherosclerotic plaque characteristics in intracranial and extracranial carotid arteries with severity of white matter hyperintensities (WMHs) in symptomatic patients using magnetic resonance (MR) imaging.
Patients with cerebrovascular symptoms and carotid plaque were recruited from the cross-sectional, multicenter study of CARE-II. Luminal stenosis of intracranial and extracranial carotid arteries, carotid plaque compositional features, and WMHs were evaluated by brain structural and vascular MR imaging. The atherosclerotic plaque characteristics in intracranial and extracranial carotid arteries were compared between patients with and without moderate-to-severe WMHs (Fazekas score > 2), and their associations with severity of WMHs were analyzed using logistic regression.
Of the recruited 622 patients (mean age, 58.7 ± 10.9 years; 422 males), 221 (35.5 %) had moderate-to-severe WMHs with higher prevalence of moderate-to-severe luminal stenosis (17.0 % vs. 10.4 %), intraplaque hemorrhage (15.7 % vs. 9.0 %), thin/ruptured fibrous cap (30.2 % vs. 20.4 %), calcification (44.4 % vs. 22.2 %) and lipid-rich necrotic core (63.8 % vs. 51.1 %) in carotid artery compared to those without (all P < 0.05). Multivariate logistic regression showed that carotid calcification (OR, 1.854; 95 % CI, 1.187–2.898; P = 0.007) was independently associated with moderate-to-severe WMHs after adjusting for confounding factors. No significant association was found between intracranial atherosclerotic stenosis and moderate-to-severe WMHs (P > 0.05).
Carotid atherosclerotic plaque features, particularly presence of calcification, were independently associated with severity of WMHs, but such association was not found in intracranial atherosclerotic stenosis, suggesting that carotid atherosclerotic plaque characteristics may have closer association with severity of WMHs compared to intracranial atherosclerosis.
White matter hyperintensity volume modifies the association between CSF vascular inflammatory biomarkers and regional FDG-PET along the Alzheimer's disease continuum
2023, Neurobiology of Aging
In older adults with abnormal levels of Alzheimer’s disease neuropathology, lower cerebrospinal fluid (CSF) vascular endothelial growth factor (VEGF) levels are associated with lower [¹⁸F]-fluorodeoxyglucose positron emission tomography (FDG-PET) signal, but whether this association is (1) specific to VEGF or broadly driven by vascular inflammation, or (2) modified by vascular risk (e.g., white matter hyperintensities [WMHs]) remains unknown. To address this and build upon our past work, we evaluated whether 5 CSF vascular inflammation biomarkers (vascular cell adhesion molecule 1, VEGF, C-reactive protein, fibrinogen, and von Willebrand factor)—previously associated with CSF amyloid levels—were related to FDG-PET signal and whether WMH volume modified these associations in 158 Alzheimer’s Disease Neuroimaging Initiative participants (55–90 years old, 39 cognitively normal, 80 mild cognitive impairment, 39 Alzheimer’s disease). We defined regions both by cortical boundary and by the 3 major vascular territories: anterior, middle, and posterior cerebral arteries. We found that WMH volume had interactive effects with CSF biomarkers (VEGF and C-reactive protein) on FDG-PET throughout the cortex in both vascular territories and conventionally defined regions of interest.
The correlation between medial pattern of intracranial arterial calcification and white matter hyperintensities
2023, Atherosclerosis
Despite reported correlations between intracranial arterial calcification (IAC) and white matter hyperintensities (WMH), little is known about the relationship between IAC pattern and WMH. By differentiating intimal and medial IAC, we aimed to investigate the relationship between IAC pattern and WMH.
Consecutive acute stroke patients were included. IAC pattern was categorized as intimal or medial on plain brain CT. The number of cerebral arteries involved by IAC for each patient was recorded. IAC severity was defined as focal or diffuse. On brain MRI, the burden of WMH was visually graded and classified as absent mild, moderate and severe. Multiple logistic regression was performed to examine the relationship between IAC and WMH.
Among 265 patients, intimal IAC was detected in 54.7% patients and medial IAC in 48.5% patients. Diffuse IAC was present in 27.9% patients, all of which were medial. WMH was found in 75.5% patients, including 39.6% patients with mild WMH, 26.0% with moderate WMH, and 9.8% with severe WMH. The severity of medial IAC was correlated with WMH occurrence (p < 0.001). Chi-square linear trend suggested the number of arteries involved by medial IAC (p < 0.001) and the severity of medial IAC (p < 0.001) were correlated with WMH burden. Multiple ordinal logistic regression demonstrated a positive correlation of WMH burden with the number of arteries involved by medial IAC (p < 0.001) and the severity of medial IAC (p < 0.001).
Medial IAC was correlated with WMH. The dose-effect relationship between medial IAC and WMH suggests underlying shared mechanisms of intracranial large artery disease and small vessel disease.
Cerebral white matter hyperintensity is associated with intracranial atherosclerosis in a healthy population
2017, Atherosclerosis
Citation Excerpt :
Although the exact pathophysiologic mechanisms of WMH are unknown, it has been thought to have a similar pathophysiologic mechanism as lacunar infarction, being different from large artery disease [3–5]. Recently, many studies have shown that WMH commonly coexists in ischemic stroke patients who have large artery disease, especially intracranial atherosclerosis (ICAS) [2,6,7]. Increased blood-brain barrier permeability, resulting from endothelial dysfunction, and hypoperfusion, resulting from large vessel occlusion, have been suggested, although there is still a lack of conclusive evidence [8,9].
Cerebral white matter hyperintensity (WMH) is commonly found in ischemic stroke patients, especially when accompanied by intracranial atherosclerosis (ICAS). However, the relationship between WMH and ICAS in a healthy population has not been evaluated.
A total of 3159 healthy subjects who underwent health checkups, including brain magnetic resonance imaging and angiography, were enrolled. ICAS was defined as an occlusion or more than 50% stenosis of intracranial vessels on magnetic resonance angiography. Volumes of WMH were quantitatively rated.
Eighty-two (2.6%) subjects had ICAS. The mean age of the cohort was 56 years, and the median volume of WMH was 1.02 [0.20–2.60] mL. In a multivariate analysis, ICAS [β = 0.331, 95% confidence interval (CI) = 0.086 to 0.576, p = 0.008] was significantly associated with WMH volumes after adjusting confounders. Age (β = 0.046, 95% CI = 0.042 to 0.050, p < 0.001), hypertension (β = 0.113, 95% CI = 0.017 to 0.210, p = 0.021), and diabetes (β = 0.154, 95% CI = 0.043 to 0.265, p = 0.006) were also significant, independently of ICAS. The ICAS (+) group had more frequent vascular risk factors including hypertension, diabetes, and statin use, than the ICAS (−) group, and these tendencies increased when WMH was accompanied by ICAS.
ICAS is associated with larger WMH volume in a healthy population. Close observation of this group and strict control of vascular risk factors are needed.
Clinical effect of cerebrovascular atherosclerosis on cognition in Alzheimer's disease
2016, Archives of Gerontology and Geriatrics
Citation Excerpt :
The EC and IC groups were defined in the following ways: (1) the EC group included patients with significant stenotic lesions in extracranial arteries, such as the internal carotid arteries (ICAs) proximal to the ophthalmic segment of the ICA or the extracranial vertebral arteries (n = 18) with or without intracranial arterial stenosis. ( 2) The IC group included patients who had significant stenotic lesions in intracranial ICAs, which were defined as being distal to the clinoid segment of the ICA, intracranial vertebral arteries, the basilar artery, the middle cerebral arteries (MCAs), the anterior cerebral arteries (ACAs), or the posterior cerebral arteries (PCAs) with or without extracranial arterial stenosis (n = 43) (Lee et al., 2011). When the contrast-filling defect of the affected side was more than 50% greater than that of the contralateral side on computed tomography (CT) angiography, the site was considered to be a “significant stenosis.”
The association between cerebrovascular atherosclerosis and Alzheimer’s disease (AD) has been examined in many cross-sectional studies; however, there are few data regarding the role of cerebrovascular atherosclerosis on the longitudinal course of cognitive decline in AD. The aim of this study was to examine the progression of cognitive function in AD patients with cerebrovascular atherosclerosis compared to those without atherosclerosis over a two-year period.
Forty-seven AD patients with cerebrovascular atherosclerosis and 81 AD patients without atherosclerosis were assessed for cognitive function at the time of diagnosis and again at follow-up after two years. The cognitive functions were evaluated by neuropsychological tests including mini-mental state examination (MMSE) and clinical dementia scale (CDR).
Repeated-measures multivariate analyses showed that there was a significant group-by-time interactions for the temporal changes of the MMSE and CDR between the two groups. The group-by-time interactions remained significant when the atherosclerotic patients were sub-classified into either an extracranial stenosis (EC) group or an intracranial stenosis(IC) group. Comparing either the EC or IC group with the non-atherosclerosis group, there were no main effects by time or group alone, but there were significant group-by-time interactions for the MMSE and CDR.
Cognitive function worsened more in terms of progressive impairment in AD patients with cerebrovascular atherosclerosis compared to AD patients without cerebrovascular atherosclerosis, regardless of whether the atherosclerosis was extracranial or intracranial.
The cross-sectional and longitudinal relationships between white matter hyperintensities and dementia in patients with Parkinson's disease: A retrospective analysis of 132 patients in a single center
2016, Archives of Gerontology and Geriatrics
Citation Excerpt :
There are a number of plausible explanations underlying the relationship between WMH and cognitive impairment in PD patients. First, a WMH-prevalent brain area is vulnerable to brain ischemia because of its location on a watershed zone (Norrving, 2015; Caplan & Hennerici, 1998; Lee et al., 2011). Non-vascular (orthostatic hypotension) or vascular factors predisposed PD patients to developing WMH in the brain area (Norrving, 2015; Matsubayashi et al., 1997; Pantoni & Garcia, 1997).
To clarify the cross-sectional and longitudinal relationships between white matter hyperintensities (WMH) and dementia in Parkinson’s disease (PD) patients.
One hundred thirty-two PD patients were included. Using medical records, the patient data including Hoehn and Yahr stage, postural instability, neuropsychological tests and magnetic resonance imaging were analyzed. The degree of WMH was rated according to a modified Fazekas scale. The relationship between the variables and dementia was analyzed using the independent t-test, the chi-square test, logistic regression analysis and the Cox proportional hazard model.
The mean age of the study patients (35 males and 97 females) was 71.6 years (range, 45–93 years). The baseline WMH was associated not only cross-sectionally with the contemporary prevalence of dementia but also longitudinally with subsequent occurrence of dementia in the univariate analysis. These relationships became attenuated and statistically insignificant in the multivariate analysis after adjusting for confounders. It was postural instability that consistently predicted dementia in both the cross-sectional and the longitudinal data.
Our study showed that baseline WMH was not independently associated with dementia, and instead postural instability revealed at first examination can be a more reliable predictor of dementia in PD patients.

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White matter hyperintensities (WMH) are associated with intracranial atherosclerosis rather than extracranial atherosclerosis

Abstract

Introduction

Section snippets

Patients

Results

Discussion

Conflict of interest statement

Eur. J. Vasc. Endovasc. Surg.

Lancet

BMC Neurol.

J. Neurol. Sci.

Classification of subtype of acute ischemic stroke. Definitions for use in a multicenter clinical trial. TOAST. Trial of Org 10172 in Acute Stroke Treatment

Stroke

Brain white matter hyperintensities are associated with carotid intraplaque hemorrhage

Radiology

Leukoencephalopathy in patients with ischemic stroke

Stroke

Intracranial branch atheromatous disease: a neglected, understudied, and underused concept

Neurology

Impaired clearance of emboli (washout) is an important link between hypoperfusion, embolism, and ischemic stroke

Arch. Neurol.

Carotid atherosclerosis and cerebral white matter lesions in a population based magnetic resonance imaging study

J. Neurol.

Pathologic correlates of incidental MRI white matter signal hyperintensities

Neurology

Chinese-white differences in the distribution of occlusive cerebrovascular disease

Neurology