White matter damage in frontotemporal lobar degeneration spectrum

Cereb Cortex. 2012 Dec;22(12):2705-14. doi: 10.1093/cercor/bhr288. Epub 2011 Oct 10.


White matter (WM) tract damage was assessed in patients with the behavioral variant frontotemporal dementia (bvFTD) and the 3 primary progressive aphasia (PPA) variants and compared with the corresponding brain atrophy patterns. Thirteen bvFTD and 20 PPA patients were studied. Tract-based spatial statistics and voxel-based morphometry were used. Patients with bvFTD showed widespread diffusion tensor magnetic resonance imaging (DT MRI) abnormalities affecting most of the WM bilaterally. In PPA patients, WM damage was more focal and varied across the 3 syndromes: left frontotemporoparietal in nonfluent, left frontotemporal in semantic, and left frontoparietal in logopenic patients. In each syndrome, DT MRI changes extended beyond the topography of gray matter loss. Left uncinate damage was the best predictor of frontotemporal lobar degeneration diagnosis versus controls. DT MRI measures of the anterior corpus callosum and left superior longitudinal fasciculus differentiated bvFTD from nonfluent cases. The best predictors of semantic PPA compared with both bvFTD and nonfluent cases were diffusivity abnormalities of the left uncinate and inferior longitudinal fasciculus. This study provides insights into the similarities and differences of WM damage in bvFTD and PPA variants. DT MRI metrics hold promise to serve as early markers of WM integrity loss that only at a later stage may be detectable by volumetric measures.

MeSH terms

  • Aged
  • Aphasia, Primary Progressive / pathology*
  • Atrophy
  • Brain / pathology*
  • Diagnosis, Differential
  • Diffusion Tensor Imaging / methods*
  • Female
  • Frontotemporal Lobar Degeneration / pathology*
  • Humans
  • Male
  • Middle Aged
  • Nerve Fibers, Myelinated / pathology*
  • Reproducibility of Results
  • Sensitivity and Specificity