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

BMJ 2010; 341 doi: https://doi.org/10.1136/bmj.c3666 (Published 26 July 2010) Cite this as: BMJ 2010;341:c3666
  1. Stéphanie Debette, neurologist and research fellow123,
  2. H S Markus, professor of neurology1
  1. 1Clinical Neuroscience, St George’s University of London, London
  2. 2Department of Neurology, Boston University School of Medicine, B601, 72 East Concord Street, Boston, MA 02118, USA
  3. 3Department of Neurology, EA2691, Lille University Hospital, Lille, France
  1. Correspondence to: S Debette sdebette{at}bu.edu
  • Accepted 20 May 2010

Abstract

Objectives To review the evidence for an association of white matter hyperintensities with risk of stroke, cognitive decline, dementia, and death.

Design Systematic review and meta-analysis.

Data sources PubMed from 1966 to 23 November 2009.

Study selection 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.

Data extraction 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.

Data synthesis 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.

Conclusion 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.

Footnotes

  • We thank for their collaboration F Pasquier, S Bombois, and D Leys (Department of Neurology, Lille University Hospital, France); PA Wolf, S Seshadri, A Beiser, and R Au (Department of Neurology, Boston University School of Medicine), and C DeCarli (University of California at Davis).

  • Contributors: SD did the literature search, wrote the first draft, and prepared the tables and some figures. HSM did the literature search, revised the draft manuscript, and prepared some of the figures. SD and HSM are guarantors.

  • Funding: SD was supported by a grant from the European Neurological Society, a Fulbright grant, and an award from the Bettencourt-Schueller and the Lilly foundations.

  • Competing interests: All authors have completed the unified competing interest form at http://www.icmje.org/coi_disclosure.pdf (available on request from the corresponding author) and declare that: (1) SD was supported by a grant from the European Neurological Society, a Fulbright grant, and an award from the Bettencourt-Schueller and the Lilly foundations; (2) SD and HSM have no relationship with companies that might have an interest in the submitted work in the previous 3 years; (3) that their spouses, partners, or children have no financial relationships that may be relevant to the submitted work; and (4) that they have no non-financial interests that may be relevant to the submitted work.

  • Ethical approval: Not required.

  • Data sharing: Additional data not available.

  • Accepted 20 May 2010

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