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

Alexander N.W. Taylor, Lana M. Kambeitz-Ilankovic, Benno Gesierich, Lee Simon-Vermot, Nicolai Franzmeier, Miguel Á. Araque Caballero, Sophia Müller, Liu Hesheng, Birgit Ertl-Wagner, Katharina Bürger, Michael W. Weiner, Martin Dichgans, Marco Duering, Michael Ewers, Alzheimer's Disease Neuroimaging Initiative

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Introduction: 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.

Method: 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).

Results: 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.

Conclusions: 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 and Dementia
Issue number3
Early online date16 Jul 2016
Publication statusPublished - 1 Mar 2017


  • Alzheimer's disease
  • Functional connectivity
  • Fiber tract
  • Resting-state fMRI
  • White matter hyperintensities
  • Vascular
  • Amyloid-beta

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