Please use this identifier to cite or link to this item: http://bura.brunel.ac.uk/handle/2438/26192
Title: Cerebellar and subcortical atrophy contribute to psychiatric symptoms in frontotemporal dementia
Authors: Bussy, A
Levy, JP
Best, T
Patel, R
Cupo, L
Van Langenhove, T
Nielsen, JE
Pijnenburg, Y
Waldö, ML
Remes, AM
Schroeter, ML
Anderl‐Straub, S
Rollin, A
Tábuas‐Pereira, M
Kuchcinski, G
Bertoux, M
Lebouvier, T
Deramecourt, V
Russell, LL
Rowe, JB
Timberlake, C
Cantoni, V
Afonso, S
Seelaar, H
Engel, A
Polyakova, M
Bocchetta, M
Rossi, G
Vandenberghe, R
Bocchetta, M
Synofzik, M
Moreno, F
Arighi, A
Todd, E
de Mendonça, A
Sanchez‐Valle, R
van Swieten, JC
Laforce, R
Langheinrich, T
Gerhard, A
Graff, C
Giaccone, G
Shafei, R
Prioni, S
Finger, E
Benotmane, H
Tartaglia, MC
Masellis, M
Di Fede, G
Papma, JM
Devenyi, GA
Convery, RS
Chakravarty, MM
Ducharme, S
Fenoglio, C
Esteve, AS
Bessi, V
Zetterberg, H
Nelson, A
Bouzigues, A
Heller, C
Greaves, CV
Giannini, L
Caroppo, P
Swift, IJ
Scarpini, E
Veldsman, M
Nicholas, J
Jelic, V
Verdelho, A
Cope, T
Tiraboschi, P
Rittman, T
Benussi, A
Andersson, C
Villanua, J
Fumagalli, G
Premi, E
Gasparotti, R
Archetti, S
Gazzina, S
Maruta, C
van Minkelen, R
Borracci, V
Cañada, M
Thonberg, H
Alves, P
Poesen, K
Redaelli, V
Pijnenburg, Y
Tang‐Wai, D
Rogaeva, E
Tainta, M
Funkiewiez, A
Castelo‐Branco, M
Öijerstedt, L
Freedman, M
Keren, R
Rosa‐Neto, P
Ferreira, CB
Black, S
Mitchell, S
Nacmias, B
Shoesmith, C
Bartha, R
Rademakers, R
Poos, J
Rinaldi, D
Zulaica, M
Prix, C
Ferrari, C
Miltenberger, G
Polito, C
Lombardi, G
Saracino, D
Santiago, B
Thompson, P
Barandiaran, M
Langheinrich, T
Lladó, A
Gauthier, S
Antonell, A
Santana, I
do Couto, FS
Olives, J
Balasa, M
Bargalló, N
Borrego‐Ecija, S
Duro, D
Colliot, O
Gabilondo, A
Camuzat, A
Pasquier, F
Gorostidi, A
Le Ber, I
Butler, CR
Bender, B
Sayah, S
Wilke, C
Graf, L
Otto, M
Tiraboschi, P
Brice, A
Vogels, A
Vandenbulcke, M
Van Damme, P
Bruffaerts, R
Sorbi, S
Leitão, MJ
Bertrand, A
Galimberti, D
Danek, A
Rohrer, JD
Cash, D
Wlasich, E
Almeida, MR
Wagemann, O
Loosli, S
Borroni, B
Samra, K
Schönecker, S
Levin, J
Hoegen, T
Lombardi, J
Thomas, DL
Jiskoot, L
Keywords: frontotemporal dementia;genetics;magnetic resonance imaging;neuropsychiatry
Issue Date: 9-Mar-2023
Publisher: Wiley
Citation: Bussy, A. et al. on behalf of GENetic Frontotemporal dementia Initiative (GENFI) (2023) 'Cerebellar and subcortical atrophy contribute to psychiatric symptoms in frontotemporal dementia', Human Brain Mapping, 44 (7), pp. 2684 - 2700. doi: 10.1002/hbm.26220.
Abstract: Copyright © 2023 The Authors. 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.
Description: Data Availability Statement: The data that support the findings of this study are available on request via https://www.genfi.org/study/ or by emailing genfi@ucl.ac.uk. The data are not publicly available due to privacy or ethical restrictions.
Supporting Information: available online at: https://onlinelibrary.wiley.com/doi/10.1002/hbm.26220#support-information-section .
URI: https://bura.brunel.ac.uk/handle/2438/26192
DOI: https://doi.org/10.1002/hbm.26220
ISSN: 1065-9471
Other Identifiers: ORCID iDs: Aurélie Bussy https://orcid.org/0000-0001-6695-9941; Jørgen E. Nielsen https://orcid.org/0000-0003-0453-5582; Barbara Borroni https://orcid.org/0000-0001-9340-9814; Martina Bocchetta https://orcid.org/0000-0003-1814-5024; Gabriel A. Devenyi https://orcid.org/0000-0002-7766-1187.
Appears in Collections:Dept of Life Sciences Research Papers

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