title: Patterns of regional cerebellar atrophy in genetic frontotemporal dementia.
abstract: BACKGROUND
  Frontotemporal dementia (FTD) is a heterogeneous neurodegenerative disorder with a strong genetic component. The cerebellum has not traditionally been felt to be involved in FTD but recent research has suggested a potential role.
  
  
  METHODS
  We investigated the volumetry of the cerebellum and its subregions in a cohort of 44 patients with genetic FTD (20 MAPT, 7 GRN, and 17 C9orf72 mutation carriers) compared with 18 cognitively normal controls. All groups were matched for age and gender. On volumetric T1-weighted magnetic resonance brain images we used an atlas propagation and label fusion strategy of the Diedrichsen cerebellar atlas to automatically extract subregions including the cerebellar lobules, the vermis and the deep nuclei.
  
  
  RESULTS
  The global cerebellar volume was significantly smaller in C9orf72 carriers (mean (SD): 99989 (8939) mm(3)) compared with controls (108136 (7407) mm(3)). However, no significant differences were seen in the MAPT and GRN carriers compared with controls (104191 (6491) mm(3) and 107883 (6205) mm(3) respectively). Investigating the individual subregions, C9orf72 carriers had a significantly lower volume than controls in lobule VIIa-Crus I (15% smaller, p < 0.0005), whilst MAPT mutation carriers had a significantly lower vermal volume (10% smaller, p = 0.001) than controls. All cerebellar subregion volumes were preserved in GRN carriers compared with controls.
  
  
  CONCLUSIONS
  There appears to be a differential pattern of cerebellar atrophy in the major genetic forms of FTD, being relatively spared in GRN, localized to the lobule VIIa-Crus I in the superior-posterior region of the cerebellum in C9orf72, the area connected via the thalamus to the prefrontal cortex and involved in cognitive function, and localized to the vermis in MAPT, the 'limbic cerebellum' involved in emotional processing.
authors.affiliation: Dementia Research Centre, Department of Neurodegenerative Disease, UCL Institute of Neurology, Queen Square, London, UK.
authors.forename: Martina
authors.initials: M
authors.lastname: Bocchetta
authors.affiliation: Dementia Research Centre, Department of Neurodegenerative Disease, UCL Institute of Neurology, Queen Square, London, UK; Translational Imaging Group, Centre for Medical Image Computing (CMIC), University College London, UK.
authors.forename: M Jorge
authors.initials: MJ
authors.lastname: Cardoso
authors.affiliation: Dementia Research Centre, Department of Neurodegenerative Disease, UCL Institute of Neurology, Queen Square, London, UK; Translational Imaging Group, Centre for Medical Image Computing (CMIC), University College London, UK.
authors.forename: David M
authors.initials: DM
authors.lastname: Cash
authors.affiliation: Translational Imaging Group, Centre for Medical Image Computing (CMIC), University College London, UK.
authors.forename: Sebastien
authors.initials: S
authors.lastname: Ourselin
authors.affiliation: Dementia Research Centre, Department of Neurodegenerative Disease, UCL Institute of Neurology, Queen Square, London, UK.
authors.forename: Jason D
authors.initials: JD
authors.lastname: Warren
authors.affiliation: Dementia Research Centre, Department of Neurodegenerative Disease, UCL Institute of Neurology, Queen Square, London, UK. Electronic address: j.rohrer@ucl.ac.uk.
authors.forename: Jonathan D
authors.initials: JD
authors.lastname: Rohrer
mesh_terms: D000328:Adult; D000368:Aged; D001284:Atrophy / Q000000981:diagnostic imaging / Q000209:etiology / Q000473:pathology; D000073885:C9orf72 Protein; D016022:Case-Control Studies; D002531:Cerebellum / Q000000981:diagnostic imaging / Q000473:pathology*; D005260:Female; D057180:Frontotemporal Dementia / Q000150:complications* / Q000000981:diagnostic imaging / Q000235:genetics / Q000473:pathology*; D006801:Humans; D007091:Image Processing, Computer-Assisted; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000235:genetics; D000077153:Progranulins; D011506:Proteins / Q000235:genetics; D016875:tau Proteins / Q000235:genetics
chemical_list: D000073885:C9orf72 Protein; C568651:C9orf72 protein, human; C492314:GRN protein, human; D036341:Intercellular Signaling Peptides and Proteins; C054369:MAPT protein, human; D000077153:Progranulins; D011506:Proteins; D016875:tau Proteins
keywords: C9orf72; Cerebellum; Genetic frontotemporal dementia