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White matter lesions rather than amyloid-β burden are associated with cognitive decline in Alzheimer's disease

Hiroo Kasahara1, Masaki Ikeda2, Kouki Makioka1

  • 1Department of Neurology, Gunma University Graduate School of Medicine, Maebashi, Japan.

Journal of Alzheimer'S Disease : JAD
|February 16, 2025
PubMed

Insights

In Alzheimer's disease (AD), white matter lesion severity strongly predicts cognitive decline, while amyloid-beta accumulation does not. Managing vascular risk factors is key to preventing cognitive decline in AD patients.

Area of Science:

  • Neuroscience
  • Neurology
  • Radiology

Background:

  • Alzheimer's disease (AD) is a progressive neurodegenerative disorder.
  • Amyloid-beta (Aβ) accumulation and white matter lesions (WML) are common brain pathologies in AD.
  • The distinct contributions of Aβ and WML to cognitive decline in AD require further elucidation.

Purpose of the Study:

  • To assess the severity of Aβ accumulation and WML in the brain.
  • To investigate the association between Aβ burden, WML severity, and cognitive decline in AD patients.
  • To determine the relative impact of Aβ and WML on cognitive decline in AD.

Main Methods:

  • Utilized amyloid positron emission tomography (PET) to quantify Aβ accumulation, calculating the mean cortical standardized uptake value ratio (mcSUVR).
  • Employed magnetic resonance imaging (MRI) to determine the percentage of WML area relative to brain parenchymal area.
  • Correlated Aβ burden (mcSUVR) and WML severity with measures of cognitive decline in 47 AD patients.

Main Results:

  • A significant positive correlation was observed between WML severity and cognitive decline (r=0.50, p=0.042).
  • No significant correlation was found between Aβ accumulation (mcSUVR) and cognitive decline.
  • WML severity emerged as a significant predictor of cognitive decline in this AD cohort.

Conclusions:

  • White matter lesion severity, rather than amyloid-beta accumulation, is significantly associated with cognitive decline in Alzheimer's disease.
  • These findings underscore the importance of addressing cerebrovascular health in managing cognitive decline in AD.
  • Interventions targeting vascular risk factors may be crucial for preventing or slowing cognitive decline in patients with Alzheimer's disease.
Keywords:
Alzheimer's diseasePittsburgh Compound Bamyloid-βdementiapositron emission tomographywhite matter lesion

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