• Leila Sellami, Martina Bocchetta, Mario Masellis, David M Cash, Katrina M Dick, John van Swieten, Barbara Borroni, Daniela Galimberti, Maria Carmela Tartaglia, James B Rowe, Caroline Graff, Fabrizio Tagliavini, Giovanni Frisoni, Elizabeth Finger, Alexandre de Mendonça, Sandro Sorbi, Jason D Warren, Jonathan D Rohrer, Robert Laforce, and Genetic FTD Initiative, GENFI.
• Clinique Interdisciplinaire de Mémoire(CIME), Université Laval, QC, Canada.
• J. Alzheimers Dis. 2018 Jan 1; 65 (1): 147-163.

BackgroundThe 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.ObjectiveWe aimed to identify whether NPS could be driven by distinct structural correlates.MethodsOne 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.ResultsPsychotic 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.ConclusionNeuroanatomical 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.

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