A modified Camel and Cactus Test detects presymptomatic semantic impairment in genetic frontotemporal dementia within the GENFI cohort

Katrina Moore, Rhian Convery, Martina Bocchetta, Mollie Neason, David M. Cash, Caroline Greaves, Lucy L. Russell, Mica T. M. Clarke, Georgia Peakman, John van Swieten, Lize Jiskoot, Fermin Moreno, Myriam Barandiaran, Raquel Sanchez-Valle, Barbara Borroni, Robert Laforce, Marie-Claire Dore, Mario Masellis, Maria Carmela Tartaglia, Caroline GraffDaniela Galimberti, James B. Rowe, Elizabeth Finger, Matthis Synofzik, Hans-Otto Karnath, Rik Vandenberghe, Alexandre de Mendonca, Carolina Maruta, Fabrizio Tagliavini, Isabel Santana, Simon Ducharme, Chris Butler, Alex Gerhard, Johannes Levin, Adrian Danek, Markus Otto, Jason D. Warren, Jonathan D. Rohrer, Martin N. Rossor, Nick C. Fox, Ione O. C. Woollacott, Rachelle Shafei, Carolin Heller, Rita Guerreiro, Jose Bras, David L. Thomas, Jennifer Nicholas, Simon Mead, Lieke Meeter, Jessica Panman, Janne Papma, Rick van Minkelen, Yolande Pijnenburg, Begona Indakoetxea, Alazne Gabilondo, Mikel Tainta, Maria de Arriba, Ana Gorostidi, Miren Zulaica, Jorge Villanua, Zigor Diaz, Sergi Borrego-Ecija, Jaume Olives, Albert Llado, Mircea Balasa, Anna Antonell, Nuria Bargallo, Enrico Premi, Maura Cosseddu, Stefano Gazzina, Alessandro Padovani, Roberto Gasparotti, Silvana Archetti, Sandra Black, Sara Mitchell, Ekaterina Rogaeva, Morris Freedman, Ron Keren, David Tang-Wa, Linn Oijerstedt, Christin Andersson, Vesna Jelic, Hakan Thonberg, Andrea Arighi, Chiara Fenoglio, Elio Scarpini, Giorgio Fumagalli, Thomas Cope, Carolyn Timberlake, Timothy Rittman, Christen Shoesmith, Robart Bartha, Rosa Rademakers, Carlo Wilke, Benjamin Bender, Rose Bruffaerts, Philip Van Damme, Mathieu Vandenbulcke, Catarina B. Ferreira, Gabriel Miltenberger, Ana Verdelho, Sonia Afonso, Ricardo Taipa, Paola Caroppo, Giuseppe Di Fede, Giorgio Giaccone, Sara Prioni, Veronica Redaelli, Giacomina Rossi, Pietro Tiraboschi, Diana Duro, Maria Rosario Almeida, Miguel Castelo-Branco, Maria Joao Leitao, Miguel Tabuas-Pereira, Beatriz Santiago, Serge Gauthier, Pedro Rosa-Neto, Michele Veldsman, Toby Flanagan, Catharina Prix, Tobias Hoegen, Elisabeth Wlasich, Sandra Loosli, Sonja Schonecker, Elisa Semler, Sarah Anderl-Straub

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Abstract

Impaired semantic knowledge is a characteristic feature of some forms of frontotemporal dementia (FTD), particularly the sporadic disorder semantic dementia. Less is known about semantic cognition in the genetic forms of FTD caused by mutations in the genes MAPT, C9orf72, and GRN. We developed a modified version of the Camel and Cactus Test (mCCT) to investigate the presence of semantic difficulties in a large genetic FTD cohort from the Genetic FTD Initiative (GENFI) study. Six-hundred-forty-four participants were tested with the mCCT including 67 MAPT mutation carriers (15 symptomatic, and 52 in the presymptomatic period), 165 GRN mutation carriers (33 symptomatic, 132 presymptomatic), and 164 C9orf72 mutation carriers (56 symptomatic, 108 presymptomatic) and 248 mutation-negative members of FTD families who acted as a control group. The presymptomatic mutation carriers were further split into those early and late in the presymptomatic period (more than vs. within 10 years of expected symptom onset). Groups were compared using a linear regression model, adjusting for age and education, with bootstrapping. Performance on the mCCT had a weak negative correlation with age (rho = -0.20) and a weak positive correlation with education (rho = 0.13), with an overall abnormal score (below the 5th percentile of the control population) being below 27 out of a total of 32. All three of the symptomatic mutation groups scored significantly lower than controls: MAPT mean 22.3 (standard deviation 8.0), GRN 24.4 (7.2), C9orf72 23.6 (6.5) and controls 30.2 (1.6). However, in the presymptomatic groups, only the late MAPT and late C9orf72 mutation groups scored lower than controls (28.8 (2.2) and 28.9 (2.5) respectively). Performance on the mCCT correlated strongly with temporal lobe volume in the symptomatic MAPT mutation group (rho > 0.80). In the C9orf72 group, mCCT score correlated with both bilateral temporal lobe volume (rho > 0.31) and bilateral frontal lobe volume (rho > 0.29), whilst in the GRN group mCCT score correlated only with left frontal lobe volume (rho = 0.48). This study provides evidence for presymptomatic impaired semantic knowledge in genetic FTD. The different neuroanatomical associations of the mCCT score may represent distinct cognitive processes causing deficits in different groups: loss of core semantic knowledge associated with temporal lobe atrophy (particularly in the MAPT group), and impaired executive control of semantic information associated with frontal lobe atrophy. Further studies will be helpful to address the longitudinal change in mCCT performance and the exact time at which presymptomatic impairment occurs.
Original languageEnglish
Pages (from-to)112-119
Number of pages8
JournalApplied neuropsychology. Adult
Volume29
Issue number1
Early online date5 Feb 2020
DOIs
Publication statusPublished - 2 Jan 2022

Bibliographical note

Funding
JDR is an MRC Clinician Scientist (MR/M008525/1) and has received funding from the NIHR Rare Diseases Translational Research
Collaboration [BRC149/NS/MH], the Bluefield Project and the Association for Frontotemporal Degeneration. JDW receives grant support from the Alzheimer’s Society and Alzheimer’s Research UK. RSV has received funding from Fundacio Marat o de TV3 [20143810].

© 2020 Taylor & Francis Group, LLC

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