title: TDP-43 subtypes are associated with distinct atrophy patterns in frontotemporal dementia.
abstract: BACKGROUND
  We sought to describe the antemortem clinical and neuroimaging features among patients with frontotemporal lobar degeneration with TDP-43 immunoreactive inclusions (FTLD-TDP).
  
  
  METHODS
  Subjects were recruited from a consecutive series of patients with a primary neuropathologic diagnosis of FTLD-TDP and antemortem MRI. Twenty-eight patients met entry criteria: 9 with type 1, 5 with type 2, and 10 with type 3 FTLD-TDP. Four patients had too sparse FTLD-TDP pathology to be subtyped. Clinical, neuropsychological, and neuroimaging features of these cases were reviewed. Voxel-based morphometry was used to assess regional gray matter atrophy in relation to a group of 50 cognitively normal control subjects.
  
  
  RESULTS
  Clinical diagnosis varied between the groups: semantic dementia was only associated with type 1 pathology, whereas progressive nonfluent aphasia and corticobasal syndrome were only associated with type 3. Behavioral variant frontotemporal dementia and frontotemporal dementia with motor neuron disease were seen in type 2 or type 3 pathology. The neuroimaging analysis revealed distinct patterns of atrophy between the pathologic subtypes: type 1 was associated with asymmetric anterior temporal lobe atrophy (either left- or right-predominant) with involvement also of the orbitofrontal lobes and insulae; type 2 with relatively symmetric atrophy of the medial temporal, medial prefrontal, and orbitofrontal-insular cortices; and type 3 with asymmetric atrophy (either left- or right-predominant) involving more dorsal areas including frontal, temporal, and inferior parietal cortices as well as striatum and thalamus. No significant atrophy was seen among patients with too sparse pathology to be subtyped.
  
  
  CONCLUSIONS
  FTLD-TDP subtypes have distinct clinical and neuroimaging features, highlighting the relevance of FTLD-TDP subtyping to clinicopathologic correlation.
authors.affiliation: Dementia Research Centre, UCL Institute of Neurology, University College London, Queen Square, London, UK.
authors.forename: J D
authors.initials: JD
authors.lastname: Rohrer
authors.forename: F
authors.initials: F
authors.lastname: Geser
authors.forename: J
authors.initials: J
authors.lastname: Zhou
authors.forename: E D
authors.initials: ED
authors.lastname: Gennatas
authors.forename: M
authors.initials: M
authors.lastname: Sidhu
authors.forename: J Q
authors.initials: JQ
authors.lastname: Trojanowski
authors.forename: S J
authors.initials: SJ
authors.lastname: Dearmond
authors.forename: B L
authors.initials: BL
authors.lastname: Miller
authors.forename: W W
authors.initials: WW
authors.lastname: Seeley
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D001037:Aphasia / Q000473:pathology; D001284:Atrophy; D001921:Brain / Q000378:metabolism* / Q000473:pathology*; D004268:DNA-Binding Proteins / Q000145:classification / Q000378:metabolism*; D005260:Female; D005625:Frontal Lobe / Q000378:metabolism / Q000473:pathology; D057180:Frontotemporal Dementia / Q000378:metabolism* / Q000473:pathology*; D057174:Frontotemporal Lobar Degeneration / Q000378:metabolism / Q000473:pathology; D006801:Humans; D002479:Inclusion Bodies / Q000378:metabolism; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D013702:Temporal Lobe / Q000378:metabolism / Q000473:pathology; D013788:Thalamus / Q000378:metabolism / Q000473:pathology
chemical_list: D004268:DNA-Binding Proteins