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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    • "Frequently the ageing brain is characterised by areas of hyperintense signal known as white matter hyperintsities (WMH) seen in the WM on T2 weighted MRI scans, particularly using the Fluid Attenuation Inversion Recovery (FLAIR) sequence (Grueter and Schulz 2012; O'Sullivan 2008). The WMH load is associated with age and a number of comorbities such as stroke and cognitive decline (Debette and Markus 2010). Ischemia is considered as a leading pathological feature of WMH (Fernando et al. 2006; O'Sullivan 2008) and a reduction in perfusion during hypercapnic challenge has been shown within tissue with a high density of WM lesions in elderly subjects, suggesting a possible causative link between selective hypoxia in watershed zones and white matter damage (Mandell et al. 2008). "
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    ABSTRACT: In late age, the autonomic nervous system (ANS) has diminished ability to maintain physiological homeostasis in the brain in response to challenges such as to systemic blood pressure changes caused by standing. We devised an fMRI experiment aiming to map the cerebral effects of an ANS challenge (Valsalva manoeuvre (VM)). We used dual-echo fMRI to measure the effective transverse relaxation rate (R2*, which is inversely proportional to brain tissue oxygenation levels) in 45 elderly subjects (median age 80 years old, total range 75-89) during performance of the VM. In addition, we collected fluid-attenuated inversion recovery (FLAIR) data from which we quantified white matter hyperintensity (WMH) volumes. We conducted voxelwise analysis of the dynamic changes in R2* during the VM to determine the distribution of oxygenation changes due to the autonomic stressor. In white matter, we observed significant decreases in oxygenation levels. These effects were predominantly located in posterior white matter and to a lesser degree in the right anterior brain, both concentrated around the border zones (watersheds) between cerebral perfusion territories. These areas are known to be particularly vulnerable to hypoxia and are prone to formation of white matter hyperintensities. Although we observed overlap between localisation of WMH and triggered deoxygenation on the group level, we did not find significant association between these independent variables using subjectwise statistics. This could suggest other than recurrent transient hypoxia mechanisms causing/contributing to the formation of WMH.
    Journal of the American Aging Association 10/2015; 37(5). DOI:10.1007/s11357-015-9833-6 · 3.39 Impact Factor
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    • "WMHs have themselves been shown to be an independent risk factor for future stroke (hazard ratio 3.3, 95% CI: 2.6–4.4) (Debette and Markus, 2010). However, measurements of cerebrovascular function such as cerebral blood flow (CBF) and cerebrovascular reactivity (CVR) may provide more sensitive and direct measures of CVD than these structural markers (Glodzik et al., 2011). "
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    ABSTRACT: Late-onset epilepsy (LOE), with onset after 50 years of age, is often attributed to underlying occult cerebrovascular disease. LOE is associated with a three-fold increase in subsequent stroke risk, therefore it is important to improve our understanding of pathophysiology. In this exploratory study, we aimed to determine whether established structural magnetic resonance imaging markers and novel physiological imaging markers of occult cerebrovascular disease were more common in patients with LOE than age-matched controls.
    Clinical neuroimaging 08/2015; 9:128-33. DOI:10.1016/j.nicl.2015.07.016 · 2.53 Impact Factor
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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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