Faster Cortical Thinning and Surface Area Loss in Presymptomatic and Symptomatic C9orf72 Repeat Expansion Adult Carriers. Issue 1 (12th May 2020)

• Record Type: Journal Article
• Authors: Le Blanc, Gabriella; Jetté Pomerleau, Vincent; McCarthy, Jillian; Borroni, Barbara; van Swieten, John; Galimberti, Daniela; Sanchez‐Valle, Raquel; LaForce, Robert; Moreno, Fermin; Synofzik, Matthis; Graff, Caroline; Masellis, Mario; Tartaglia, Maria C.; Rowe, James B.; Vandenberghe, Rik; Finger, Elizabeth; Tagliavini, Fabrizio; de Mendonça, Alexandre; Santana, Isabel; Butler, Chris; Gerhard, Alex; Danek, Adrian; Levin, Johannes; Otto, Markus; Frisoni, Giovanni; Sorbi, Sandro; Rohrer, Jonathan D.; Ducharme, Simon
• Other Names: Almeida Maria Rosario investigator.; Anderl‐Straub Sarah investigator.; Andersson Christin investigator.; Antonell Anna investigator.; Arighi Andrea investigator.; Balasa Mircea investigator.; Barandiaran Myriam investigator.; Bargalló Nuria investigator.; Bartha Robart investigator.; Bender Benjamin investigator.; Benussi Luisa investigator.; Binetti Giuliano investigator.; Black Sandra investigator.; Bocchetta Martina investigator.; Borrego Sergi investigator.; Bras Jose investigator.; Bruffaerts Rose investigator.; Caroppo Paola investigator.; Cash David investigator.; Castelo‐Branco Miguel investigator.; Convery Rhian investigator.; Cope Thomas investigator.; de Arriba María investigator.; Di Fede Giuseppe investigator.; Díaz Zigor investigator.; Dick Katrina M investigator.; Duro Diana investigator.; Fenoglio Chiara investigator.; Ferreira Carlos investigator.; Ferreira Catarina B. investigator.; Flanagan Toby investigator.; Fox Nick investigator.; Freedman Morris investigator.; Fumagalli Giorgio investigator.; Gabilondo Alazne investigator.; Gauthier Serge investigator.; Ghidoni Roberta investigator.; Giaccone Giorgio investigator.; Gorostidi Ana investigator.; Greaves Caroline investigator.; Guerreiro Rita investigator.; Heller Carolin investigator.; Hoegen Tobias investigator.; Indakoetxea Begoña investigator.; Jelic Vesna investigator.; Jiskoot Lize investigator.; Karnath Hans‐Otto investigator.; Keren Ron investigator.; Leitão Maria João investigator.; Lladó Albert investigator.; Lombardi Gemma investigator.; Loosli Sandra investigator.; Maruta Carolina investigator.; Mead Simon investigator.; Meeter Lieke investigator.; Miltenberger Gabriel investigator.; van Minkelen Rick investigator.; Mitchell Sara investigator.; Nacmias Benedetta investigator.; Neason Mollie investigator.; Nicholas Jennifer investigator.; Öijerstedt Linn investigator.; Olives Jaume investigator.; Panman Jessica investigator.; Papma Janne investigator.; Patzig Maximilian investigator.; Pievani Michela investigator.; Pijnenburg Yolande investigator.; Prioni Sara investigator.; Prix Catharina investigator.; Rademakers Rosa investigator.; Redaelli Veronica investigator.; Rittman Tim investigator.; Rogaeva Ekaterina investigator.; Rosa‐Neto Pedro investigator.; Rossi Giacomina investigator.; Rossor Martin investigator.; Santiago Beatriz investigator.; Scarpini Elio investigator.; Semler Elisa investigator.; Shafei Rachelle investigator.; Shoesmith Christen investigator.; Tábuas‐Pereira Miguel investigator.; Tainta Mikel investigator.; Tang‐Wai David investigator.; Thomas David L investigator.; Thonberg Hakan investigator.; Timberlake Carolyn investigator.; Tiraboschi Pietro investigator.; Vandamme Philip investigator.; Vandenbulcke Mathieu investigator.; Veldsman Michele investigator.; Verdelho Ana investigator.; Villanua Jorge investigator.; Warren Jason investigator.; Wilke Carlo investigator.; Zetterberg Henrik investigator.; Zulaica Miren investigator.;
• Is Part Of: Annals of neurology. Volume 88:Issue 1(2020)
• Page Start: 113
• Page End: 122
• Publication Date: 2020-05-12
• Subjects: Neurology -- Periodicals; Pediatric neurology -- Periodicals; Nervous system -- Surgery -- Periodicals; 616.8
• DOI: 10.1002/ana.25748
• Languages: English
• ISSNs: 0364-5134

Abstract

Abstract : Objective: C9orf72 expansion is the most common genetic cause of frontotemporal dementia (FTD). We examined aging trajectories of cortical thickness (CTh) and surface area in C9orf72 expansion adult carriers compared to healthy controls to characterize preclinical cerebral changes leading to symptoms. Methods: Data were obtained from the Genetic Frontotemporal Dementia Initiative. T1‐weighted magnetic resonance imaging scans were processed with CIVET 2.1 to extract vertex‐wide CTh and cortical surface area (CSA). Symptomatic and presymptomatic subjects were compared to age‐matched controls using mixed‐effects models, controlling for demographic variables. Aging trajectories were compared between carriers and noncarriers by testing the "age by genetic status" interaction. False discovery rate corrections were applied to all vertex‐wide analyses. Results: The sample included 640 scans from 386 subjects, including 54 symptomatic C9orf72 carriers (72.2% behavioral variant FTD), 83 asymptomatic carriers, and 249 controls (age range = 18–86 years). Symptomatic carriers showed fairly symmetric reduction in CTh/CSA in most of the frontal lobes, in addition to large temporoparietal areas. Presymptomatic subjects had reduced CTh/CSA in more restricted areas of the medial frontoparietal lobes, in addition to scattered lateral frontal, parietal, and temporal areas. These differences were explained by faster cortical thinning linearly throughout adulthood in a similar anatomical distribution, with differences emerging in the early 30s. CSA reduction was also faster in mutation carriers predominantly in the ventrofrontal regions. Interpretation: C9orf72 mutation carriers have faster cortical thinning and surface loss throughout adulthood in regions that show atrophy in symptomatic subjects. This suggests that the pathogenic effects of the mutation lead to structural cerebral changes decades prior to symptoms. ANN NEUROL 2020 ANN NEUROL 2020;88:113–122