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Cerebral white matter rarefaction has both neurodegenerative and vascular causes and may primarily be a distal

Thomas G Beach1, Lucia I Sue1, Sarah Scott1

  • 1Banner Sun Health Research Institute, Sun City, Arizona, USA.

Journal of Neuropathology and Experimental Neurology
|April 18, 2023
PubMed

Insights

Cerebral white matter rarefaction (CWMR) is linked to neurodegenerative diseases like Alzheimer's and cerebrovascular issues. Braak neurofibrillary stage is the strongest predictor, suggesting CWMR is a distal axonopathy, not just small vessel disease.

Area of Science:

  • Neuropathology
  • Neurodegenerative Diseases
  • Cerebrovascular Disease

Background:

  • Cerebral white matter rarefaction (CWMR) has historical links to cerebrovascular disease and is increasingly observed in Alzheimer's disease (AD).
  • The distinct roles of AD and cerebrovascular pathology in causing CWMR remain unclear.
  • Recent imaging and neuropathological studies highlight CWMR's prevalence in AD.

Purpose of the Study:

  • To investigate the neuropathological and vascular factors contributing to cerebral white matter rarefaction (CWMR).
  • To determine the relative contributions of neurodegeneration and cerebrovascular disease to CWMR.
  • To clarify the pathological basis and clinical implications of CWMR.

Main Methods:

  • Utilized large-format brain sections from 1181 autopsies in the Arizona Study of Aging and Neurodegenerative Disorders (AZSAND).
  • Graded CWMR and assessed vascular (lacunar infarcts, microinfarcts) and neurodegenerative (Braak neurofibrillary stage) correlates.
  • Employed multivariable logistic regression to identify predictors of CWMR.

Main Results:

  • CWMR was more severe in nearly all neurodegenerative disease groups compared to controls.
  • Braak neurofibrillary stage was the strongest predictor of CWMR.
  • Independent predictors included age, lacunar/microinfarcts, BMI, and female sex, indicating additive or independent roles for AD and vascular pathology.

Conclusions:

  • CWMR is strongly associated with neurodegenerative diseases, particularly Alzheimer's, and cerebrovascular pathology.
  • Braak stage is the primary driver, suggesting CWMR is a distal axonopathy.
  • CWMR should not be solely attributed to small vessel disease or considered pathognomonic for vascular dementia.
Keywords:
Alzheimer diseaseHyperintensityLacunar infarctLeukoaraiosisMicroscopic infarctSmall vessel diseaseVascular cognitive impairment

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