Objective Frontotemporal dementia (FTD) is typically associated with changes in behaviour, language and movement. However, recent studies have shown that patients can also develop an abnormal response to pain, either heightened or diminished. We aimed to investigate this symptom in mutation carriers within the Genetic FTD Initiative (GENFI).
Methods Abnormal responsiveness to pain was measured in 462 GENFI participants: 281 mutation carriers and 181 mutation-negative controls. Changes in responsiveness to pain were scored as absent (0), questionable or very mild (0.5), mild (1), moderate (2) or severe (3). Mutation carriers were classified into C9orf72 (104), GRN (128) and MAPT (49) groups, and into presymptomatic and symptomatic stages. An ordinal logistic regression model was used to compare groups, adjusting for age and sex. Voxel-based morphometry was performed to identify neuroanatomical correlates of abnormal pain perception.
Results Altered responsiveness to pain was present to a significantly greater extent in symptomatic C9orf72 expansion carriers than in controls: mean score 0.40 (SD 0.71) vs 0.00 (0.04), reported in 29% vs 1%. No significant differences were seen between the other symptomatic groups and controls, or any of the presymptomatic mutation carriers and controls. Neural correlates of altered pain perception in C9orf72 expansion carriers were the bilateral thalamus and striatum as well as a predominantly right-sided network of regions involving the orbitofrontal cortex, inferomedial temporal lobe and cerebellum.
Conclusion Changes in pain perception are a feature of C9orf72 expansion carriers, likely representing a disruption in somatosensory, homeostatic and semantic processing, underpinned by atrophy in a thalamo-cortico-striatal network.
- frontotemporal dementia
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Collaborators Martin N. Rossor, Nick C. Fox, Ione O.C. Woollacott, Rachelle Shafei, Carolin Heller, Georgia Peakman, Imogen J. Swift, Emily Todd, Rita Guerreiro, Jose Bras, David L. Thomas, Jennifer Nicholas, Simon Mead, Lize Jiskoot Lieke Meeter, Jessica Panman, Janne Papma, Rick van Minkelen, Yolande Pijnenburg, Myriam Barandiaran, Begoña Indakoetxea, Alazne Gabilondo, Mikel Tainta, Maria de Arriba, Ana Gorostidi, Miren Zulaica, Jorge Villanua, Zigor Diaz, Sergi Borrego-Ecija, Jaume Olives, Albert Lladó, 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-Wai, Linn Öijerstedt, 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, Hans-Otto Karnarth, Benjamin Bender, Rose Bruffaerts, Philip Vandamme, Mathieu Vandenbulcke, Catarina B. Ferreira, Gabriel Miltenberger, Carolina Maruta, Ana Verdelho, Sónia 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 João Leitão, 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.
Contributors RC, MB and JR contributed to the study design, acquisition, analysis and interpretation of the data as well as drafting and revising the manuscript. All other authors (CVG, KM, DMc, JCVS, FM, RS-V, BB, RJrL, MM, MCT, CG, DG, JBR, EF, MS, RV, AdeM, FT, IS, SD, CRB, AG, JL, AD, MO, JW) contributed to the acquisition of data and study coordination as well as helping to critically review and revise the manuscript.
Competing interests None declared.
Patient consent for publication Not required.
Ethics approval The study was approved by the local ethics committees and all participants gave their consent to take part.
Provenance and peer review Not commissioned; externally peer reviewed.
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