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

Alzheimers Dement. 2017 Mar;13(3):225-235. doi: 10.1016/j.jalz.2016.06.2358. Epub 2016 Jul 16.

Abstract

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.

Keywords: Alzheimer's disease; Amyloid-beta; Fiber tract; Functional connectivity; Resting-state fMRI; Vascular; White matter hyperintensities.

MeSH terms

  • Aged
  • Aged, 80 and over
  • Alzheimer Disease / diagnostic imaging
  • Alzheimer Disease / pathology*
  • Alzheimer Disease / physiopathology*
  • Brain Mapping*
  • Female
  • Humans
  • Image Processing, Computer-Assisted
  • Magnetic Resonance Imaging
  • Male
  • Nerve Net / diagnostic imaging
  • Nerve Net / pathology*
  • Neuropsychological Tests
  • Positron-Emission Tomography
  • White Matter / diagnostic imaging
  • White Matter / pathology*