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  • Review Article
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White matter hyperintensities, cognitive impairment and dementia: an update

Nature Reviews Neurology volume 11, pages 157–165 (2015)Cite this article

Subjects

Key Points

  • White matter hyperintensities (WMHs) are commonly seen on brain MRI in older people, and result from chronic ischaemia associated with cerebral small vessel disease

  • The histopathology of WMHs is heterogeneous, with tissue damage ranging from slight disentanglement of the matrix to varying degrees of myelin and axonal loss

  • This heterogeneity might partly explain the weak clinicoradiological associations found in patients with WMHs

  • WMHs cause cognitive decline—in particular of information processing speed—and may lead to executive dysfunction and, ultimately, dementia

  • Although progression of WMHs has been associated with dementia and dependency, little evidence is available that reduction of WMH progression can prevent functional decline

Abstract

White matter hyperintensities (WMHs) in the brain are the consequence of cerebral small vessel disease, and can easily be detected on MRI. Over the past three decades, research has shown that the presence and extent of white matter hyperintense signals on MRI are important for clinical outcome, in terms of cognitive and functional impairment. Large, longitudinal population-based and hospital-based studies have confirmed a dose-dependent relationship between WMHs and clinical outcome, and have demonstrated a causal link between large confluent WMHs and dementia and disability. Adequate differential diagnostic assessment and management is of the utmost importance in any patient, but most notably those with incipient cognitive impairment. Novel imaging techniques such as diffusion tensor imaging might reveal subtle damage before it is visible on standard MRI. Even in Alzheimer disease, which is thought to be primarily caused by amyloid, vascular pathology, such as small vessel disease, may be of greater importance than amyloid itself in terms of influencing the disease course, especially in older individuals. Modification of risk factors for small vessel disease could be an important therapeutic goal, although evidence for effective interventions is still lacking. Here, we provide a timely Review on WMHs, including their relationship with cognitive decline and dementia.

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Figure 1: Visual rating of WMHs according to Scheltens.20
Figure 2: Axial fluid-attenuated inversion recovery images illustrating the Fazekas scores.
Figure 3: Direct matching of WMHs on postmortem MRI scans and histochemically stained sections.
Figure 4: Direct matching of WMHs on postmortem MRI scans and histochemically stained sections.

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Authors and Affiliations

  1. Department of Neurology, Alzheimer Center, VU University Medical Center, Neuroscience Campus Amsterdam, De Boelelaan 1117, Amsterdam, 1081 HV, Netherlands

    Niels D. Prins & Philip Scheltens

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  1. Niels D. Prins
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  2. Philip Scheltens
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Both authors researched data for the article, discussed the content, wrote the article, and reviewed and edited the manuscript before submission.

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Correspondence to Philip Scheltens.

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The authors declare no competing financial interests.

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Prins, N., Scheltens, P. White matter hyperintensities, cognitive impairment and dementia: an update. Nat Rev Neurol 11, 157–165 (2015). https://doi.org/10.1038/nrneurol.2015.10

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