Debette S., Markus H.S. The clinical importance of white matter hyperintensities on brain magnetic resonance imaging: systematic review and meta-analysis. BMJ, 341, C3666

Clinical Neuroscience, St George's University of London, London.
BMJ (online) (Impact Factor: 17.45). 07/2010; 341(jul26 1):c3666. DOI: 10.1136/bmj.c3666
Source: PubMed


To review the evidence for an association of white matter hyperintensities with risk of stroke, cognitive decline, dementia, and death.
Systematic review and meta-analysis.
PubMed from 1966 to 23 November 2009.
Prospective longitudinal studies that used magnetic resonance imaging and assessed the impact of white matter hyperintensities on risk of incident stroke, cognitive decline, dementia, and death, and, for the meta-analysis, studies that provided risk estimates for a categorical measure of white matter hyperintensities, assessing the impact of these lesions on risk of stroke, dementia, and death.
Population studied, duration of follow-up, method used to measure white matter hyperintensities, definition of the outcome, and measure of the association of white matter hyperintensities with the outcome.
46 longitudinal studies evaluated the association of white matter hyperintensities with risk of stroke (n=12), cognitive decline (n=19), dementia (n=17), and death (n=10). 22 studies could be included in a meta-analysis (nine of stroke, nine of dementia, eight of death). White matter hyperintensities were associated with an increased risk of stroke (hazard ratio 3.3, 95% confidence interval 2.6 to 4.4), dementia (1.9, 1.3 to 2.8), and death (2.0, 1.6 to 2.7). An association of white matter hyperintensities with a faster decline in global cognitive performance, executive function, and processing speed was also suggested.
White matter hyperintensities predict an increased risk of stroke, dementia, and death. Therefore white matter hyperintensities indicate an increased risk of cerebrovascular events when identified as part of diagnostic investigations, and support their use as an intermediate marker in a research setting. Their discovery should prompt detailed screening for risk factors of stroke and dementia.

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    • "This study demonstrates that WMH in periventricular and deep white matter are associated with decreased gray matter CBF and structural profiles in regions that are remote from the WMH lesions . The etiology of WMH remains a topic of intense research ( Thompson and Hakim , 2009 ; Debette and Markus , 2010 ; Gibson et al . , 2010 ; Uh et al . "
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    ABSTRACT: Cerebral White Matter Hyperintensities (WMH) are associated with vascular risk factors and age-related cognitive decline. WMH have primarily been associated with global white matter and gray matter (GM) changes and less is known about regional effects in GM. The purpose of this study was to test for an association between WMH and two GM imaging measures: cerebral blood flow (CBF) and voxel-based morphometry (VBM). Twenty-six elderly adults with mild to severe WMH participated in this cross-sectional 3 Tesla magnetic resonance imaging (MRI) study. MRI measures of GM CBF and VBM were derived from arterial spin labeling (ASL) and T1-weighted images, respectively. Fluid-attenuated inversion recovery (FLAIR) images were used to quantify the WMH lesion burden (mL). GM CBF and VBM data were used as dependent variables. WMH lesion burden, age and sex were used in a regression model. Visual rating of WMH with the Fazekas method was used to compare the WMH lesion volume regression approach. WMH volume was normally distributed for this group (mean volume of 22.7 mL, range: 2.2-70.6 mL). CBF analysis revealed negative associations between WMH volume and CBF in the left anterior putamen, subcallosal, accumbens, anterior caudate, orbital frontal, anterior insula, and frontal pole (corrected p < 0.05). VBM analysis revealed negative associations between WMH and GM volume in lingual gyrus, intracalcarine, and bilateral hippocampus (corrected p < 0.05). The visual rating scale corroborated the regression findings (corrected p < 0.05). WMH lesion volume was associated with intra-group GM CBF and structural differences in this cohort of WMH adults with mild to severe lesion burden.
    Frontiers in Aging Neuroscience 07/2015; 7:131. DOI:10.3389/fnagi.2015.00131 · 4.00 Impact Factor
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    • "WMH have been detected in over 90% of large cohorts of subjects in their sixties [S€ oderlund et al., 2003; Wen and Sachdev, 2004]. WMH increase the risk of stroke, even after adjustment for known associated vascular risk factors such as hypertension and smoking [Debette and Markus, 2010], suggesting the presence of WMH are associated with a pathological vascular state. In support of this, people with WMH have been demonstrated to have reduced CBF and cerebrovascular reactivity [Hatazawa et al., 1997; Kawamura et al., 1993; Kobari et al., 1990; Marstrand et al., 2002]. "
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    ABSTRACT: Blood oxygenation level-dependent (BOLD) signal changes are often assumed to directly reflect neural activity changes. Yet the real relationship is indirect, reliant on numerous assumptions, and subject to several sources of noise. Deviations from the core assumptions of BOLD contrast functional magnetic resonance imaging (fMRI), and their implications, have been well characterized in healthy populations, but are frequently neglected in stroke populations. In addition to conspicuous local structural and vascular changes after stroke, there are many less obvious challenges in the imaging of stroke populations. Perilesional ischemic changes, remodeling in regions distant to lesion sites, and diffuse perfusion changes all complicate interpretation of BOLD signal changes in standard fMRI protocols. Most stroke patients are also older than the young populations on which assumptions of neurovascular coupling and the typical analysis pipelines are based. We present a review of the evidence to show that the basic assumption of neurovascular coupling on which BOLD-fMRI relies does not capture the complex changes arising from stroke, both pathological and recovery related. As a result, estimating neural activity using the canonical hemodynamic response function is inappropriate in a number of contexts. We review methods designed to better estimate neural activity in stroke populations. One promising alternative to event-related fMRI is a resting-state-derived functional connectivity approach. Resting-state fMRI is well suited to stroke populations because it makes no performance demands on patients and is capable of revealing network-based pathology beyond the lesion site. Hum Brain Mapp, 2014. © 2014 Wiley Periodicals, Inc. © 2014 Wiley Periodicals, Inc.
    Human Brain Mapping 04/2015; 36(4). DOI:10.1002/hbm.22711 · 5.97 Impact Factor
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    • "Previously, LA is only considered as a common brain neuroimaging phenomenon that is associated with the risk of cognitive decline, incident stroke, gait disturbance and falls, and dementia ( Garde et al., 2005 ; Ross et al., 2005 ; Au et al., 2006 ; Bokura et al., 2006 ; O &apos; Sullivan, 2008 ; Buyck et al., 2009 ; Debette and Markus, 2010 ). Pathologically , LA is predominantly considered to represent incomplete ischemia, with the following common pathological characterizations: widespread perivascular rarefaction of myelin, patchy demyelination, partial loss of axons and oligodendroglial cells, mild reactive astrocytic gliosis, and sparsely distributed macrophages as well as disruption of ependyma ( Brun and Englund, 1986 ; Babikian and Ropper, 1987 ; Fazekas et al., 1998 ; Pantoni, 2002 ; Kim et al., 2008 ; Schmidt et al., 2011 ). "
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    ABSTRACT: Leukoaraiosis (LA), also called white matter lesions (WMLs) and white matter hyperintensities (WMHs), is a frequent neuroimaging finding commonly seen on magnetic resonance imaging brain scans of elderly people with prevalence ranging from 50% to 100%. Although it remains asymptomatic, LA is not considered to be benign, and it is showed to be related to a host of poor clinical outcomes and increases the risk of disability, dementia, depression, stroke, and the overall morbidity and mortality. Pathologically, LA is characterized by loss of myelin and axons, patchy demyelination, and denudation of ependyma in regions of WMH. Age and hypertension are the most importantly established risk factors for LA. However, the precise pathogenic mechanisms remain unclear. Together with the previous findings, our recent genetic results strongly supported that LA is associated with immune response and neuroinflammation. Therefore, we confidently hypothesized that LA was not only a common neuroimaging phenomenon in the elderly but also an emerging neuroinflammatory disorder in the central nervous system. This article focusing on neuroimaging classification, genetics basis, and putative molecular mechanism introduced the basic knowledge and current status of LA and put forward some of our research ideas and results from our molecular genetics research, which may pave the way for deciphering the putative pathogenic mechanism, risk factor, epigenetic index, and its application in diagnostic agents or drug target for prevention and treatment. Thus, it could provide clinicians and researchers with a specific and modern overview of LA to enable the understanding of recent progress and future directions in this illness.
    Reviews in the neurosciences 03/2015; DOI:10.1515/revneuro-2014-0082 · 3.33 Impact Factor
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