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.

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.

• Authors: Shunichiro Shinagawa, Georges Naasan, Anna M Karydas, Giovanni Coppola, Mochtar Pribadi, William W Seeley, John Q Trojanowski, Bruce L Miller, Lea T Grinberg
• Journal: Journal of geriatric psychiatry and neurology (J Geriatr Psychiatry Neurol) Vol. 28 Issue 2 Pg. 99-107 (Jun 2015) ISSN: 0891-9887 [Print] United States
• PMID: 25342578 (Publication Type: Case Reports, Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
• Copyright: © The Author(s) 2014.

Chemical References

• DNA-Binding Proteins
• alpha-Synuclein
• tau Proteins

Topics

• Adult
• Aged
• Atrophy (pathology)
• Autopsy
• DNA-Binding Proteins (metabolism)
• Delusions (complications, genetics, pathology, psychology)
• Frontotemporal Dementia (complications, genetics, pathology, psychology)
• Frontotemporal Lobar Degeneration (complications, diagnosis, pathology)
• Heterozygote
• Humans
• Male
• Middle Aged
• Mutation (genetics)
• Neuroimaging
• Neurologic Examination
• Neuropsychological Tests
• Open Reading Frames (genetics)
• Parietal Lobe (pathology)
• Parkinsonian Disorders (complications, diagnosis)
• alpha-Synuclein (metabolism)
• tau Proteins (metabolism)