Tract-specific white matter hyperintensities disrupt neural network function in Alzheimer’s disease

Alexander N. W. Taylor, Lana Kambeitz-Ilankovic, Benno Gesierich, Lee Simon-Vermot, Nicolai Franzmeier, Miguel A. Araque Caballero, Sophia Meuller, Liu Hesheng, Birgit Ertl-Wagner, Katharina Beurger, Michael Weiner, Martin Dichgans, Marco Duering, Michael Ewers

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White matter hyperintensities (WMHs) increase the risk of Alzheimer's disease (AD). Whether WMHs are associated with the decline of functional neural networks in AD is debated.

Resting-state functional magnetic resonance imaging and WMH were assessed in 78 subjects with increased amyloid levels on AV-45 positron emission tomography (PET) in different clinical stages of AD. We tested the association between WMH volume in major atlas-based fiber tract regions of interest (ROIs) and changes in functional connectivity (FC) between the tracts' projection areas within the default mode network (DMN).

WMH volume within the inferior fronto-occipital fasciculus (IFOF) was the highest among all tract ROIs and associated with reduced FC in IFOF-connected DMN areas, independently of global AV-45 PET. Higher AV-45 PET contributed to reduced FC in IFOF-connected, temporal, and parietal DMN areas.

High fiber tract WMH burden is associated with reduced FC in connected areas, thus adding to the effects of amyloid pathology on neuronal network function.
Original languageEnglish
Pages (from-to)225-235
Number of pages11
JournalAlzheimer's & Dementia
Issue number3
Early online date15 Jul 2016
Publication statusPublished - 01 Mar 2017
Externally publishedYes


  • Alzheimer's disease
  • Functional connectivity
  • Fibre tract
  • resting-state fMRI
  • White matter hyperintensities
  • vascular
  • amyloid-beta
  • Resting-state fMRI
  • Fiber tract
  • Vascular
  • Amyloid-beta
  • Humans
  • Male
  • Nerve Net/diagnostic imaging
  • Positron-Emission Tomography
  • White Matter/diagnostic imaging
  • Neuropsychological Tests
  • Magnetic Resonance Imaging
  • Image Processing, Computer-Assisted
  • Aged, 80 and over
  • Brain Mapping
  • Female
  • Aged
  • Alzheimer Disease/diagnostic imaging


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