Clinicopathological Study of Patients With C9ORF72-Associated Frontotemporal Dementia Presenting With Delusions. (June 2015)

• Record Type: Journal Article
• Authors: Shinagawa, Shunichiro; Naasan, Georges; Karydas, Anna M.; Coppola, Giovanni; Pribadi, Mochtar; Seeley, William W.; Trojanowski, John Q.; Miller, Bruce L.; Grinberg, Lea T.
• Is Part Of: Journal of geriatric psychiatry and neurology. Volume 28:Number 2(2015)
• Page Start: 99
• Page End: 107
• Publication Date: 2015-06
• Subjects: C9ORF72 -- neurodegeneration -- frontotemporal dementia -- delusion -- neuropathology -- neuroimaging; Geriatric neurology -- Periodicals; Geriatric neuropsychiatry -- Periodicals; Geriatric psychiatry -- Periodicals; Nervous system -- Diseases -- Periodicals; 618.97689
• DOI: 10.1177/0891988714554710
• Languages: English
• ISSNs: 0891-9887

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. Method: 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. Result: 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. Conclusion: 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.