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Title: Cerebellar and subcortical atrophy contribute to psychiatric symptoms in frontotemporal dementia
Authors: Bussy, Aurélie
Levy, Jake P.
Best, Tristin
Patel, Raihaan
Cupo, Lani
Van Langenhove, Tim
Nielsen, Jørgen E.
Pijnenburg, Yolande
Waldö, Maria Landqvist
Remes, Anne M.
Schroeter, Matthias L.
Santana, Isabel 
Pasquier, Florence
Otto, Markus
Danek, Adrian
Levin, Johannes
Le Ber, Isabelle
Vandenberghe, Rik
Synofzik, Matthis
Moreno, Fermin
de Mendonça, Alexandre
Sánchez-Valle, Raquel 
Laforce, Robert
Langheinrich, Tobias
Gerhard, Alexander
Graff, Caroline
Butler, Chris R.
Sorbi, Sandro
Jiskoot, Lize
Seelaar, Harro
van Swieten, John C.
Finger, Elizabeth
Tartaglia, Maria Carmela
Masellis, Mario
Tiraboschi, Pietro
Galimberti, Daniela
Borroni, Barbara
Rowe, James B.
Bocchetta, Martina
Rohrer, Jonathan D. 
Devenyi, Gabriel A.
Chakravarty, M. Mallar
Ducharme, Simon
Keywords: frontotemporal dementia; genetics; magnetic resonance imaging; neuropsychiatry
Issue Date: May-2023
Publisher: Wiley-Blackwell
Project: Alzheimer Society of Canada; Weston Brain Institute; Fonds de Recherche du Québec - Santé; MRC UK GENFI, Grant/Award Number: MR/M023664/1; Italian Ministry of Health, Grant/Award Number: CoEN015; Canadian Institutes of Health Research; Alzheimer's Society grant, Grant/Award Number: AS-PG- 16-007; Alzheimer's Society, Grant/Award Number: AS-JF-19a-004-517; NIHR Rare Diseases Translational Research Collaboration; Deutsche Forschungsgemeinschaft; NIHR Cambridge Biomedical Research Centre, Grant/Award Numbers: BRC-1215-20014, BRC149/NS/MH 
Serial title, monograph or event: Human Brain Mapping
Volume: 44
Issue: 7
Abstract: Recent studies have reported early cerebellar and subcortical impact in the disease progression of genetic frontotemporal dementia (FTD) due to microtubule-associated protein tau (MAPT), progranulin (GRN) and chromosome 9 open reading frame 72 (C9orf72). However, the cerebello-subcortical circuitry in FTD has been understudied despite its essential role in cognition and behaviors related to FTD symptomatology. The present study aims to investigate the association between cerebellar and subcortical atrophy, and neuropsychiatric symptoms across genetic mutations. Our study included 983 participants from the Genetic Frontotemporal dementia Initiative including mutation carriers and noncarrier first-degree relatives of known symptomatic carriers. Voxel-wise analysis of the thalamus, striatum, globus pallidus, amygdala, and the cerebellum was performed, and partial least squares analyses (PLS) were used to link morphometry and behavior. In presymptomatic C9orf72 expansion carriers, thalamic atrophy was found compared to noncarriers, suggesting the importance of this structure in FTD prodromes. PLS analyses demonstrated that the cerebello-subcortical circuitry is related to neuropsychiatric symptoms, with significant overlap in brain/behavior patterns, but also specificity for each genetic mutation group. The largest differences were in the cerebellar atrophy (larger extent in C9orf72 expansion group) and more prominent amygdalar volume reduction in the MAPT group. Brain scores in the C9orf72 expansion carriers and MAPT carriers demonstrated covariation patterns concordant with atrophy patterns detectable up to 20 years before expected symptom onset. Overall, these results demonstrated the important role of the subcortical structures in genetic FTD symptom expression, particularly the cerebellum in C9orf72 and the amygdala in MAPT carriers.
ISSN: 1065-9471
DOI: 10.1002/hbm.26220
Rights: openAccess
Appears in Collections:I&D CNC - Artigos em Revistas Internacionais
FMUC Medicina - Artigos em Revistas Internacionais

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