Cerebellar and subcortical atrophy contribute to psychiatric symptoms in frontotemporal dementia. Issue 7 (9th March 2023)

• Record Type: Journal Article
• 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; Sanchez‐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;
• Other Names: Esteve Aitana Sogorb investigator.; Nelson Annabel investigator.; Bouzigues Arabella investigator.; Heller Carolin investigator.; Greaves Caroline V investigator.; Cash David investigator.; Thomas David L investigator.; Todd Emily investigator.; Benotmane Hanya investigator.; Zetterberg Henrik investigator.; Swift Imogen J investigator.; Nicholas Jennifer investigator.; Samra Kiran investigator.; Russell Lucy L investigator.; Bocchetta Martina investigator.; Shafei Rachelle investigator.; Convery Rhian S investigator.; Timberlake Carolyn investigator.; Cope Thomas investigator.; Rittman Timothy investigator.; Benussi Alberto investigator.; Premi Enrico investigator.; Gasparotti Roberto investigator.; Archetti Silvana investigator.; Gazzina Stefano investigator.; Cantoni Valentina investigator.; Arighi Andrea investigator.; Fenoglio Chiara investigator.; Scarpini Elio investigator.; Fumagalli Giorgio investigator.; Borracci Vittoria investigator.; Rossi Giacomina investigator.; Giaccone Giorgio investigator.; Di Fede Giuseppe investigator.; Caroppo Paola investigator.; Tiraboschi Pietro investigator.; Prioni Sara investigator.; Redaelli Veronica investigator.; Tang‐Wai David investigator.; Rogaeva Ekaterina investigator.; Castelo‐Branco Miguel investigator.; Freedman Morris investigator.; Keren Ron investigator.; Black Sandra investigator.; Mitchell Sara investigator.; Shoesmith Christen investigator.; Bartha Robart investigator.; Rademakers Rosa investigator.; Poos Jackie investigator.; Papma Janne M. investigator.; Giannini Lucia investigator.; van Minkelen Rick investigator.; Pijnenburg Yolande investigator.; Nacmias Benedetta investigator.; Ferrari Camilla investigator.; Polito Cristina investigator.; Lombardi Gemma investigator.; Bessi Valentina investigator.; Veldsman Michele investigator.; Andersson Christin investigator.; Thonberg Hakan investigator.; Öijerstedt Linn investigator.; Jelic Vesna investigator.; Thompson Paul investigator.; Langheinrich Tobias investigator.; Lladó Albert investigator.; Antonell Anna investigator.; Olives Jaume investigator.; Balasa Mircea investigator.; Bargalló Nuria investigator.; Borrego‐Ecija Sergi investigator.; Verdelho Ana investigator.; Maruta Carolina investigator.; Ferreira Catarina B. investigator.; Miltenberger Gabriel investigator.; do Couto Frederico Simões investigator.; Gabilondo Alazne investigator.; Gorostidi Ana investigator.; Villanua Jorge investigator.; Cañada Marta investigator.; Tainta Mikel investigator.; Zulaica Miren investigator.; Barandiaran Myriam investigator.; Alves Patricia investigator.; Bender Benjamin investigator.; Wilke Carlo investigator.; Graf Lisa investigator.; Vogels Annick investigator.; Vandenbulcke Mathieu investigator.; Van Damme Philip investigator.; Bruffaerts Rose investigator.; Poesen Koen investigator.; Rosa‐Neto Pedro investigator.; Gauthier Serge investigator.; Camuzat Agnès investigator.; Brice Alexis investigator.; Bertrand Anne investigator.; Funkiewiez Aurélie investigator.; Rinaldi Daisy investigator.; Saracino Dario investigator.; Colliot Olivier investigator.; Sayah Sabrina investigator.; Prix Catharina investigator.; Wlasich Elisabeth investigator.; Wagemann Olivia investigator.; Loosli Sandra investigator.; Schönecker Sonja investigator.; Hoegen Tobias investigator.; Lombardi Jolina investigator.; Anderl‐Straub Sarah investigator.; Rollin Adeline investigator.; Kuchcinski Gregory investigator.; Bertoux Maxime investigator.; Lebouvier Thibaud investigator.; Deramecourt Vincent investigator.; Santiago Beatriz investigator.; Duro Diana investigator.; Leitão Maria João investigator.; Almeida Maria Rosario investigator.; Tábuas‐Pereira Miguel investigator.; Afonso Sónia investigator.; Engel Annerose investigator.; Polyakova Maryna investigator.;
• Is Part Of: Human brain mapping. Volume 44:Issue 7(2023)
• Page Start: 2684
• Page End: 2700
• Publication Date: 2023-03-09
• Subjects: frontotemporal dementia -- genetics -- magnetic resonance imaging -- neuropsychiatry; Brain mapping -- Periodicals; 611.81
• DOI: 10.1002/hbm.26220
• Languages: English
• ISSNs: 1065-9471

Abstract

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. Abstract : The present study aims to investigate the association between cerebellar and subcortical atrophy, and neuropsychiatric symptoms across genetic mutations. Voxel‐wise analysis of the thalamus, striatum, globus pallidus, amygdala, and the cerebellum was performed, and partial least squares analyses were used to link morphometry and behavior. Our 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.