What is white matter disease?

White Matter Disease

White matter disease refers to chronic microvascular ischemic changes in the brain's white matter that appear as hyperintensities on MRI, affecting approximately 50% of people in their 40s and over 90% of people in their 60s. 1

Definition and Appearance

• White matter hyperintensities (WMHs) appear as bright spots on T2/FLAIR MRI sequences due to slightly increased water content 1
• They represent varying degrees of myelin loss, axonal rarefaction, edema, perivascular space dilation, gliosis, and microvascular disease 2
• Characteristic imaging features include:
  • Linear hyperintensities parallel to ventricles
  • Symmetric periventricular "capping"
  • Lesions smaller than 3mm in longest axis 1

Prevalence and Risk Factors

• Highly prevalent with aging: 50.9% in ages 40-49 and 96.6% by ages 60-69 2
• Primary risk factors include:
  • Hypertension
  • Diabetes
  • Smoking
  • Advanced age 1
• Less common etiologies include inflammatory/autoimmune conditions, vasculitis, thrombophilic disorders, migraine with aura, and genetic small vessel diseases 1

Clinical Significance

• WMHs represent a core feature of cerebral small vessel disease (SVD) along with lacunar infarcts, enlarged perivascular spaces, and microbleeds 2
• They are associated with:
  • Increased risk of stroke and mortality 1
  • Cognitive impairment, particularly in executive function and processing speed 1
  • All-cause dementia 1
  • Vascular dementia (VaD) 2

Cognitive Impact

• Executive function impairments are most consistently associated with WMHs, especially frontal WMHs 1
• Processing speed decline and global cognitive function reduction are common 1
• WMHs can affect memory, though associations have been less consistent compared to executive function 2
• Recent evidence shows that WMH regression is associated with preserved global cognition and improved executive function, suggesting potential for tissue recovery 3

Diagnostic Considerations

• MRI is more sensitive than CT for detecting white matter disease 2
• Advanced imaging techniques (diffusion tensor imaging, arterial spin labeling, magnetization transfer imaging) can reveal subtle damage before it is visible on standard MRI 1
• WMHs are particularly prevalent in small vessel stroke compared to other stroke subtypes 4
• The pattern and distribution of WMHs can help differentiate between various conditions:
  • Periventricular WMHs are strongly associated with cognitive decline 1
  • Deep gray nuclei involvement suggests chronic hypertension 2
  • Peripheral involvement and superficial siderosis may indicate cerebral amyloid angiopathy 2

Management Recommendations

• Control of vascular risk factors:
  • Blood pressure control (target <130/80 mmHg)
  • Cholesterol management (LDL <70 mg/dL)
  • Blood sugar control (HbA1c <7%)
  • Smoking cessation 1
• Healthy lifestyle measures:
  • Regular physical activity (150 minutes of moderate exercise weekly)
  • Mediterranean or DASH diet
  • Adequate sleep (7-8 hours nightly)
  • Stress reduction techniques 1
• Baseline cognitive assessment and annual cognitive follow-up 1
• Follow-up MRI in 12 months to assess for WMH progression or regression 1

Future Directions

• Research is ongoing to develop specific treatments for white matter disease 5
• Emerging approaches include molecular, cellular, metabolic, and behavioral interventions 5
• Identification and validation of biomarkers are key steps for treatment development 5
• Prevention trials focusing on risk factor management and healthy lifestyle may help mitigate disease incidence 5