title: MRI signatures of the frontotemporal lobar degeneration continuum.
abstract: OBJECTIVE
  To identify overlapping and unique grey (GM) and white matter (WM) signatures within the frontotemporal lobar degeneration (FTLD) continuum, and discriminate likely FTLD-TAU and FTLD-TDP patients using structural and diffusion tensor (DT) magnetic resonance imaging (MRI).
  
  
  METHODS
  T1-weighted and DT MRI were collected from 121 subjects: 35 motor neuron disease (MND), 14 behavioral variant of frontotemporal dementia, 12 semantic and 11 nonfluent primary progressive aphasia, 21 progressive supranuclear palsy syndrome patients, and 28 healthy controls. Patterns of GM atrophy were established using voxel-based morphometry. Tract-based spatial statistics was used to perform a WM voxelwise analysis of mean diffusivity and fractional anisotropy.
  
  
  RESULTS
  In all clinical FTLD phenotypes, the pattern of WM damage was more distributed than that of GM atrophy. All patient groups, with the exception of MND cases with a pure motor syndrome, shared a focal GM atrophy centered around the dorsolateral and medial frontal cortex and a largely overlapping pattern of WM damage involving the genu and body of the corpus callosum and ventral frontotemporal and dorsal frontoparietal WM pathways. Surrounding this common area, phenotype (symptom)-specific GM and WM regions of damage were found in each group.
  
  
  CONCLUSIONS
  In the FTLD spectrum, WM disruption is more severe than GM damage. Frontal cortex and WM pathways represent the common target of neurodegeneration in these conditions. The topographic pattern of damage supports a "prion-like" protein propagation through WM connections as underlying mechanism of the stereotyped progression of FTLD.
authors.affiliation: Neuroimaging Research Unit.
authors.forename: Federica
authors.initials: F
authors.lastname: Agosta
authors.affiliation: Neuroimaging Research Unit.
authors.forename: Sebastiano
authors.initials: S
authors.lastname: Galantucci
authors.affiliation: Department of Neurology, Institute of Experimental Neurology, Division of Neuroscience.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Magnani
authors.affiliation: Department of Clinical Neurosciences, San Raffaele Scientific Institute, Vita-Salute San Raffaele University, Milan, Italy.
authors.forename: Alessandra
authors.initials: A
authors.lastname: Marcone
authors.affiliation: Neuroimaging Research Unit.
authors.forename: Daniele
authors.initials: D
authors.lastname: Martinelli
authors.affiliation: Department of Neurology, Institute of Experimental Neurology, Division of Neuroscience.
authors.forename: Maria
authors.initials: M
authors.lastname: Antonietta Volontè
authors.affiliation: Department of Neurology, Institute of Experimental Neurology, Division of Neuroscience.
authors.forename: Nilo
authors.initials: N
authors.lastname: Riva
authors.affiliation: Department of Clinical Neurosciences, San Raffaele Scientific Institute, Vita-Salute San Raffaele University, Milan, Italy.
authors.forename: Sandro
authors.initials: S
authors.lastname: Iannaccone
authors.affiliation: Neuroimaging Research Unit.
authors.forename: Pilar M
authors.initials: PM
authors.lastname: Ferraro
authors.affiliation: Neuroimaging Research Unit.
authors.forename: Francesca
authors.initials: F
authors.lastname: Caso
authors.affiliation: Department of Neuroscience, ALS Center, "Rita Levi Montalcini" University of Torino, Torino, Italy.
authors.forename: Adriano
authors.initials: A
authors.lastname: Chiò
authors.affiliation: Department of Neurology, Institute of Experimental Neurology, Division of Neuroscience.
authors.forename: Giancarlo
authors.initials: G
authors.lastname: Comi
authors.affiliation: Department of Neuroradiology and CERMAC, San Raffaele Scientific Institute, Vita-Salute San Raffaele University, Milan, Italy.
authors.forename: Andrea
authors.initials: A
authors.lastname: Falini
authors.affiliation: Neuroimaging Research Unit.|Department of Neurology, Institute of Experimental Neurology, Division of Neuroscience.
authors.forename: Massimo
authors.initials: M
authors.lastname: Filippi
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001284:Atrophy / Q000473:pathology; D056324:Diffusion Tensor Imaging / Q000379:methods; D005260:Female; D057180:Frontotemporal Dementia / Q000473:pathology; D057174:Frontotemporal Lobar Degeneration / Q000473:pathology*; D066128:Gray Matter / Q000473:pathology*; D006801:Humans; D008279:Magnetic Resonance Imaging / Q000379:methods*; D008297:Male; D008875:Middle Aged; D016472:Motor Neuron Disease / Q000473:pathology*; D057178:Primary Progressive Nonfluent Aphasia / Q000473:pathology; D013494:Supranuclear Palsy, Progressive / Q000473:pathology*; D066127:White Matter / Q000473:pathology*
keywords: amyotrophic lateral sclerosis; diffusion tensor MRI; frontotemporal dementia; frontotemporal lobar degeneration; motor neuron disease; primary progressive aphasia; progressive supranuclear palsy; white matter
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