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

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

Research output: Contribution to journalArticlepeer-review

15 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 - 2016


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

ASJC Scopus subject areas

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

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