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Age-associated white matter lesions: the MRC Cognitive Function and Ageing Study

Stephen B Wharton1, Julie E Simpson, Carol Brayne

  • 1Sheffield Institute for Translational Neuroscience, University of Sheffield, Sheffield, UK.

Brain Pathology (Zurich, Switzerland)
|December 19, 2014
PubMed

Insights

White matter lesions (WML) in aging brains, linked to dementia, involve complex causes beyond ischemia. These brain abnormalities suggest a wider field effect, offering potential intervention targets.

Area of Science:

  • Neuropathology
  • Neuroimaging
  • Aging Brain Research

Background:

  • Cerebral white matter lesions (WML) are prevalent in aging brains, correlating with dementia and depression.
  • Traditionally linked to vascular factors and ischemia, WML pathogenesis is now understood to be more complex.

Purpose of the Study:

  • To investigate the complex pathogenesis of white matter lesions (WML) in the aging brain.
  • To explore cellular pathways and potential intervention targets for WML.

Main Methods:

  • Utilized post-mortem magnetic resonance imaging (MRI) on samples from the Medical Research Council Cognitive Function and Ageing Study.
  • Conducted immunohistochemical and gene expression microarray studies focusing on hypoxia-related molecules and cellular pathways.

Main Results:

  • Evidence supports a role for hypoxia/ischemia, alongside immune activation, blood-brain barrier dysfunction, metabolic pathway alterations, and glial cell injury.
  • Abnormalities were observed not only in WML but also in apparently normal white matter, indicating a field effect.

Conclusions:

  • White matter lesions (WML) represent an active pathology with a multifaceted pathogenesis.
  • The complex nature of WML suggests multiple potential targets for primary and secondary interventions in aging brains.
Keywords:
agingblood-brain barrierdementiasmall vessel diseasevascularwhite matter lesions

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