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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
Summary
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.
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