Distinct Neuroanatomical Correlates of Neuropsychiatric Symptoms in the Three Main Forms of Genetic Frontotemporal Dementia in the GENFI Cohort.
Authors
Sellami, Leila
Bocchetta, Martina
Masellis, Mario
Cash, David M
Dick, Katrina M
van Swieten, John
Borroni, Barbara
Galimberti, Daniela
Tartaglia, Maria Carmela
Rowe, James B
Graff, Caroline
Tagliavini, Fabrizio
Frisoni, Giovanni
Finger, Elizabeth
de Mendonça, Alexandre
Sorbi, Sandro
Warren, Jason D
Rohrer, Jonathan D
Laforce, Robert
Genetic FTD Initiative, GENFI
Publication Date
2018Journal Title
J Alzheimers Dis
ISSN
1387-2877
Publisher
IOS Press
Volume
65
Issue
1
Pages
147-163
Language
eng
Type
Article
Physical Medium
Print
Metadata
Show full item recordCitation
Sellami, L., Bocchetta, M., Masellis, M., Cash, D. M., Dick, K. M., van Swieten, J., Borroni, B., et al. (2018). Distinct Neuroanatomical Correlates of Neuropsychiatric Symptoms in the Three Main Forms of Genetic Frontotemporal Dementia in the GENFI Cohort.. J Alzheimers Dis, 65 (1), 147-163. https://doi.org/10.3233/JAD-180053
Abstract
BACKGROUND: The overlap between frontotemporal dementia (FTD) and primary psychiatric disorders has been brought to light by reports of prominent neuropsychiatric symptoms (NPS) in FTD-related genetic mutations, particularly among C9orf72 and GRN carriers. It has been recently demonstrated that early neuroanatomical changes in genetic FTD may be different across the major disease-causing mutations. OBJECTIVE: We aimed to identify whether NPS could be driven by distinct structural correlates. METHODS: One hundred and sixty-seven mutation carriers (75 GRN, 60 C9orf72, and 32 MAPT) were included from the Genetic FTD Initiative (GENFI) study, a large international cohort of genetic FTD. Neuropsychiatric symptoms including delusions, hallucinations (visual, auditory, and tactile), depression, and anxiety were investigated using a structured interview. Voxel-based morphometry was performed to identify neuroanatomical correlates of NPS. RESULTS: Psychotic symptoms correlated mainly with grey matter (GM) atrophy in the anterior insula, left thalamus, cerebellum, and cortical regions including frontal, parietal, and occipital lobes in GRN mutations carriers. GM atrophy in posterior structures of the default-mode network was associated with anxiety in the GRN group. Delusions in C9orf72 expansion carriers were mainly associated with left frontal cortical atrophy. Cerebellar atrophy was found to be correlated only with anxiety in C9orf72 carriers. NPS in the MAPT group were mainly associated with volume loss in the temporal lobe. CONCLUSION: Neuroanatomical correlates of NPS appear to be distinct across the main forms of genetic FTD. Overall, our findings support overlapping brain structural changes between FTD and primary psychiatric disorders.
Keywords
Genetic FTD Initiative, GENFI, Brain, Humans, tau Proteins, Magnetic Resonance Imaging, Cohort Studies, Psychotic Disorders, Mutation, Adult, Aged, Middle Aged, Female, Male, Frontotemporal Dementia, C9orf72 Protein, Progranulins
Sponsorship
Wellcome Trust (103838/Z/14/Z)
MRC (via University College London (UCL)) (523989)
Medical Research Council (MR/J009482/1)
Medical Research Council (MR/M009041/1)
Medical Research Council (MC_U105597119)
Medical Research Council (MR/M024873/1)
Medical Research Council (MC_UU_00005/12)
Identifiers
External DOI: https://doi.org/10.3233/JAD-180053
This record's URL: https://www.repository.cam.ac.uk/handle/1810/284096
Rights
Attribution-NonCommercial 4.0 International
Licence URL: https://creativecommons.org/licenses/by-nc/4.0/
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