title: Clinicopathological Study of Patients With C9ORF72-Associated Frontotemporal Dementia Presenting With Delusions.
abstract: BACKGROUND
  Several clinical studies point to a high prevalence of psychotic symptoms in frontotemporal dementia associated with C9ORF72 mutations, but clinicopathological studies addressing the association between C9ORF72 mutations and delusions are lacking.
  
  
  METHODS
  Seventeen patients with pathologically proven frontotemporal lobar degeneration (FTLD) associated with C9ORF72 mutations were identified from Neurodegenerative Disease Brain Bank. Of the 17 cases with C9ORF72 mutation, 4 exhibited well-defined delusions. The clinical history, neurological examination, neuropsychological testing, neuroimaging analysis, and postmortem assessment of the patients with delusions were evaluated and compared with the other cases.
  
  
  RESULTS
  The content of the delusions was mixed including persecution, infidelity, and grandiosity. All cases showed parkinsonism; voxel-based morphometry analysis showed greater precuneus atrophy in patients with delusions than those without delusions. All 4 had unclassifiable FTLD with TAR DNA-binding protein inclusions, with characteristics of both type A and type B. Three cases had additional τ pathology and another had α-synuclein pathology.
  
  
  CONCLUSIONS
  C9ORF72 carriers with well-defined delusions likely associated with additional pathologies and parietal atrophy in neuroimaging. Patients presenting with middle-aged onset of delusions should be screened for C9ORF72 mutations, especially if family history and parkinsonism are present.
authors.affiliation: Department of Neurology, Memory and Aging Center, University of California, San Francisco, CA, USA Department of Psychiatry, The Jikei University School of Medicine, Tokyo, Japan.
authors.forename: Shunichiro
authors.initials: S
authors.lastname: Shinagawa
authors.affiliation: Department of Neurology, Memory and Aging Center, University of California, San Francisco, CA, USA.
authors.forename: Georges
authors.initials: G
authors.lastname: Naasan
authors.affiliation: Department of Neurology, Memory and Aging Center, University of California, San Francisco, CA, USA.
authors.forename: Anna M
authors.initials: AM
authors.lastname: Karydas
authors.affiliation: Department of Psychiatry, University of California, Los Angeles, CA, USA Department of Neurology, University of California, Los Angeles, CA, USA.
authors.forename: Giovanni
authors.initials: G
authors.lastname: Coppola
authors.affiliation: Department of Psychiatry, University of California, Los Angeles, CA, USA Department of Neurology, University of California, Los Angeles, CA, USA.
authors.forename: Mochtar
authors.initials: M
authors.lastname: Pribadi
authors.affiliation: Department of Neurology, Memory and Aging Center, University of California, San Francisco, CA, USA Department of Pathology, University of California, San Francisco, CA, USA.
authors.forename: William W
authors.initials: WW
authors.lastname: Seeley
authors.affiliation: Center for Neurodegenerative Disease Research, University of Pennsylvania, Perelman School of Medicine, Philadelphia, PA, USA.
authors.forename: John Q
authors.initials: JQ
authors.lastname: Trojanowski
authors.affiliation: Department of Neurology, Memory and Aging Center, University of California, San Francisco, CA, USA.
authors.forename: Bruce L
authors.initials: BL
authors.lastname: Miller
authors.affiliation: Department of Neurology, Memory and Aging Center, University of California, San Francisco, CA, USA Department of Pathology, University of California, San Francisco, CA, USA lea.grinberg@ucsf.edu.
authors.forename: Lea T
authors.initials: LT
authors.lastname: Grinberg
mesh_terms: D000328:Adult; D000368:Aged; D001284:Atrophy / Q000473:pathology; D001344:Autopsy; D004268:DNA-Binding Proteins / Q000378:metabolism; D003702:Delusions / Q000150:complications / Q000235:genetics* / Q000473:pathology / Q000523:psychology*; D057180:Frontotemporal Dementia / Q000150:complications / Q000235:genetics* / Q000473:pathology / Q000523:psychology*; D057174:Frontotemporal Lobar Degeneration / Q000150:complications / Q000175:diagnosis / Q000473:pathology; D006579:Heterozygote; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000235:genetics*; D059906:Neuroimaging; D009460:Neurologic Examination; D009483:Neuropsychological Tests; D016366:Open Reading Frames / Q000235:genetics*; D010296:Parietal Lobe / Q000473:pathology*; D020734:Parkinsonian Disorders / Q000150:complications / Q000175:diagnosis; D051844:alpha-Synuclein / Q000378:metabolism; D016875:tau Proteins / Q000378:metabolism
chemical_list: D004268:DNA-Binding Proteins; D051844:alpha-Synuclein; D016875:tau Proteins
keywords: C9ORF72; delusion; frontotemporal dementia; neurodegeneration; neuroimaging; neuropathology