White matter lesions and brain atrophy: more than shared risk factors? A systematic review

Cerebrovasc Dis. 2009;28(3):227-42. doi: 10.1159/000226774. Epub 2009 Jul 2.


Background: White matter lesions (WML) and brain atrophy are often found on MRI in the elderly. Shared vascular risk factors may be an explanation for their concomitance. However, disturbances of white matter integrity could also be involved in the pathogenesis of brain atrophy. Our objective was to systematically review studies that investigated the relation between WML and brain atrophy on MRI, and to investigate whether there is sufficient evidence to indicate that this relation is independent of shared risk factors.

Methods: We searched PubMed for studies published in English between 1980 and October 2007, combining search terms for WML and brain atrophy. Articles that studied the relation between WML and brain atrophy were included if they met the following criteria: (1) original study, (2) MRI used for imaging, (3) assessment methods for WML and brain atrophy specified, and (4) a sample size of at least 20 participants. We recorded type and age of the study population, type and assessment of WML and brain atrophy, and variables for which adjustments were made in the analyses.

Results: We identified 48 studies that met our inclusion criteria. A significant relation between WML and brain atrophy was found in 37 out of 48 studies. The source of the study population (e.g. clinic or population based) did not affect this relation. However, only 10 studies adjusted for shared risk factors, of which 9 found an association.

Conclusions: The majority of studies found an association between WML and brain atrophy, but it is not yet clear if this association is independent of shared risk factors.

Publication types

  • Meta-Analysis
  • Review
  • Systematic Review

MeSH terms

  • Adult
  • Aged
  • Atrophy
  • Brain / pathology*
  • Cerebrovascular Disorders / epidemiology*
  • Cerebrovascular Disorders / pathology*
  • Cerebrovascular Disorders / psychology
  • Cognition Disorders / epidemiology
  • Cognition Disorders / etiology
  • Cross-Sectional Studies
  • Female
  • Humans
  • Longitudinal Studies
  • Magnetic Resonance Angiography
  • Magnetic Resonance Imaging
  • Male
  • Middle Aged
  • Risk Factors
  • Sample Size
  • Vascular Diseases / complications
  • Vascular Diseases / epidemiology