title: White matter disease correlates with lexical retrieval deficits in primary progressive aphasia.
abstract: OBJECTIVE
  To relate fractional anisotropy (FA) changes associated with the semantic and logopenic variants of primary progressive aphasia (PPA) to measures of lexical retrieval.
  
  
  METHODS
  We collected neuropsychological testing, volumetric magnetic resonance imaging, and diffusion-weighted imaging on semantic variant PPA (svPPA) (n = 11) and logopenic variant PPA (lvPPA) (n = 13) patients diagnosed using published criteria. We also acquired neuroimaging data on a group of demographically comparable healthy seniors (n = 34). FA was calculated and analyzed using a white matter (WM) tract-specific analysis approach. This approach utilizes anatomically guided data reduction to increase sensitivity and localizes results within canonically defined tracts. We used non-parametric, cluster-based statistical analysis to relate language performance to FA and determine regions of reduced FA in patients.
  
  
  RESULTS
  We found widespread FA reductions in WM for both variants of PPA. FA was related to both confrontation naming and category naming fluency performance in left uncinate fasciculus and corpus callosum in svPPA and left superior and inferior longitudinal fasciculi in lvPPA.
  
  
  CONCLUSIONS
  SvPPA and lvPPA are associated with distinct disruptions of a large-scale network implicated in lexical retrieval, and the WM disease in each phenotype may contribute to language impairments including lexical retrieval.
authors.affiliation: Department of Neurology, Penn Frontotemporal Degeneration Center, University of Pennsylvania Perelman School of Medicine , Philadelphia, PA , USA.
authors.forename: John P
authors.initials: JP
authors.lastname: Powers
authors.affiliation: Department of Neurology, Penn Frontotemporal Degeneration Center, University of Pennsylvania Perelman School of Medicine , Philadelphia, PA , USA.
authors.forename: Corey T
authors.initials: CT
authors.lastname: McMillan
authors.affiliation: Penn Image Computing and Science Laboratory, Department of Radiology, University of Pennsylvania Perelman School of Medicine , Philadelphia, PA , USA.
authors.forename: Caroline C
authors.initials: CC
authors.lastname: Brun
authors.affiliation: Penn Image Computing and Science Laboratory, Department of Radiology, University of Pennsylvania Perelman School of Medicine , Philadelphia, PA , USA.
authors.forename: Paul A
authors.initials: PA
authors.lastname: Yushkevich
authors.affiliation: Department of Computer Science, Centre for Medical Image Computing, University College London , London , UK.
authors.forename: Hui
authors.initials: H
authors.lastname: Zhang
authors.affiliation: Penn Image Computing and Science Laboratory, Department of Radiology, University of Pennsylvania Perelman School of Medicine , Philadelphia, PA , USA.
authors.forename: James C
authors.initials: JC
authors.lastname: Gee
authors.affiliation: Department of Neurology, Penn Frontotemporal Degeneration Center, University of Pennsylvania Perelman School of Medicine , Philadelphia, PA , USA.
authors.forename: Murray
authors.initials: M
authors.lastname: Grossman
keywords: diffusion-weighted MRI; frontotemporal dementia; magnetic resonance imaging; neuropsychology; primary progressive aphasia