Characterizing White Matter Tract Degeneration in Syndromic Variants of Alzheimer's Disease: A Diffusion Tensor Imaging Study

J Alzheimers Dis. 2016;49(3):633-43. doi: 10.3233/JAD-150502.


Background: Different clinical syndromes can arise from Alzheimer's disease (AD) neuropathology, including dementia of the Alzheimer's type (DAT), logopenic primary progressive aphasia (lvPPA), and posterior cortical atrophy (PCA).

Objective: To assess similarities and differences in patterns of white matter tract degeneration across these syndromic variants of AD.

Methods: Sixty-four subjects (22 DAT, 24 lvPPA, and 18 PCA) that had diffusion tensor imaging and showed amyloid-β deposition on PET were assessed in this case-control study. A whole-brain voxel-based analysis was performed to assess differences in fractional anisotropy, mean diffusivity, axial diffusivity, and radial diffusivity across groups.

Results: All three groups showed overlapping diffusion abnormalities in a network of tracts, including fornix, corpus callosum, posterior thalamic radiations, superior longitudinal fasciculus, inferior longitudinal fasciculus, inferior fronto-occipital fasciculus, and uncinate fasciculus. Subtle regional differences were also observed across groups, with DAT particularly associated with degeneration of fornix and cingulum, lvPPA with left inferior fronto-occipital fasciculus and uncinate fasciculus, and PCA with posterior thalamic radiations, superior longitudinal fasciculus, posterior cingulate, and splenium of the corpus callosum.

Conclusion: These findings show that while each AD phenotype is associated with degeneration of a specific structural network of white matter tracts, striking spatial overlap exists among the three network patterns that may be related to AD pathology.

Keywords: Alzheimer’s disease; diffusion tensor imaging; logopenic; posterior cortical atrophy; white matter.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Alzheimer Disease / classification
  • Alzheimer Disease / complications*
  • Alzheimer Disease / diagnostic imaging
  • Alzheimer Disease / pathology
  • Aniline Compounds / pharmacokinetics
  • Anisotropy
  • Aphasia, Primary Progressive / diagnostic imaging
  • Aphasia, Primary Progressive / pathology
  • Case-Control Studies
  • Diffusion Tensor Imaging*
  • Female
  • Humans
  • Image Processing, Computer-Assisted
  • Male
  • Middle Aged
  • Nerve Fibers, Myelinated / pathology*
  • Neurodegenerative Diseases / etiology*
  • Neurodegenerative Diseases / pathology*
  • Neuropsychological Tests
  • Positron-Emission Tomography
  • Psychiatric Status Rating Scales
  • Retrospective Studies
  • Thiazoles / pharmacokinetics
  • White Matter / diagnostic imaging
  • White Matter / pathology*


  • 2-(4'-(methylamino)phenyl)-6-hydroxybenzothiazole
  • Aniline Compounds
  • Thiazoles