Characterizing white matter tract degeneration in syndromic variants of Alzheimer's disease: A diffusion tensor imaging study

Ajay Madhavan, Christopher G. Schwarz, Joseph R. Duffy, Edythe A. Strand, Mary M. Machulda, Daniel A. Drubach, Kejal Kantarci, Scott A. Przybelski, Robert I. Reid, Matthew L. Senjem, Jeffrey L. Gunter, Liana G. Apostolova, Val J. Lowe, Ronald C. Petersen, Clifford R. Jack, Keith A. Josephs, Jennifer L. Whitwell

Research output: Contribution to journalArticlepeer-review

17 Scopus citations


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 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.

Original languageEnglish (US)
Pages (from-to)633-643
Number of pages11
JournalJournal of Alzheimer's Disease
Issue number3
StatePublished - 2015


  • Alzheimer's disease
  • Diffusion tensor imaging
  • Logopenic
  • Posterior cortical atrophy
  • White matter

ASJC Scopus subject areas

  • General Neuroscience
  • Clinical Psychology
  • Geriatrics and Gerontology
  • Psychiatry and Mental health


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