White matter hyperintensities influence distal cortical β-amyloid accumulation in default mode network pathways

Doaa G. Ali, Ahmed A. Bahrani, Riham H. El Khouli, Brian T. Gold, Yang Jiang, Valentinos Zachariou, Donna M. Wilcock, Gregory A. Jicha

Research output: Contribution to journalArticlepeer-review


Background and purpose: Cerebral small vessel disease (SVD) has been suggested to contribute to the pathogenesis of Alzheimer's disease (AD). Yet, the role of SVD in potentially contributing to AD pathology is unclear. The main objective of this study was to test the hypothesis that WMHs influence amyloid β (Aβ) levels within connected default mode network (DMN) tracts and cortical regions in cognitively unimpaired older adults. Methods: Regional standard uptake value ratios (SUVr) from Aβ-PET and white matter hyperintensity (WMH) volumes from three-dimensional magnetic resonance imaging FLAIR images were analyzed across a sample of 72 clinically unimpaired (mini-mental state examination ≥26), older adults (mean age 74.96 and standard deviation 8.13) from the Alzheimer's Disease Neuroimaging Initiative (ADNI3). The association of WMH volumes in major fiber tracts projecting from cortical DMN regions and Aβ-PET SUVr in the connected cortical DMN regions was analyzed using linear regression models adjusted for age, sex, ApoE, and total brain volumes. Results: The regression analyses demonstrate that increased WMH volumes in the superior longitudinal fasciculus were associated with increased regional SUVr in the inferior parietal lobule (p =.011). Conclusion: The findings suggest that the relation between Aβ in parietal cortex is associated with SVD in downstream white matter (WM) pathways in preclinical AD. The biological relationships and interplay between Aβ and WM microstructure alterations that precede overt WMH development across the continuum of AD progression warrant further study.

Original languageEnglish
Article numbere3209
JournalBrain and Behavior
Issue number10
StatePublished - Oct 2023

Bibliographical note

Publisher Copyright:
© 2023 The Authors. Brain and Behavior published by Wiley Periodicals LLC.


  • default mode network
  • neuroimaging
  • preclinical Alzheimer's disease
  • regional standardized uptake value ratio
  • white matter hyperintensities

ASJC Scopus subject areas

  • Behavioral Neuroscience


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