Social cognition impairment in genetic frontotemporal dementia within the GENFI cohort

Lucy L. Russell, Caroline V. Greaves, Martina Bocchetta, Jennifer Nicholas, Rhian S. Convery, Katrina Moore, David M. Cash, John van Swieten, Lize Jiskoot, Fermin Moreno, Raquel Sanchez-Valle, Barbara Borroni, Robert Laforce, Mario Masellis, Maria Carmela Tartaglia, Caroline Graff, Emanuela Rotondo, Daniela Galimberti, James B. Rowe, Elizabeth FingerMatthis Synofzik, Rik Vandenberghe, Alexandre de Mendonça, 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, Simon Mead, Lieke Meeter, Jessica Panman, Janne Papma, Jackie Poos, Rick van Minkelen, Yolanda 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 MPsych, Stefano Gazzina, Alessandro Padovani, Roberto Gasparotti, Silvana Archetti, Sandra Black, Sara Mitchell, Ekaterina Rogaeva, Morris Freedman, Ron Keren, Daid 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 MPsych, Ana Verdelho, S. nia Afonso, Ricardo Taipa, Paola Caroppo, Giuseppe di Fede, Giorgio Giaccone, Cristina Muscio, Sara Prioni, Veronica Redaelli, Giacomina Rossi, Pietro Tiraboschi, Diana Duro NPsych, Maria R. Almeida, Miguel Castelo-Branco, Maria J. Leitão, Miguel Tabuas-Pereira, Beatriz Santiago, Serge Gauthier, Pedro Rosa-Neto, Michele Veldsman, Paul Thompson, Tobias Langheinrich, Catharina Prix, Tobias Hoegen, Elisabeth Wlasich, Sandra Loosli, Sonja Schonecker, the Genetic FTD Initiative, GENFI, Elisa Semler, Sarah Anderl-Straub

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

Abstract

A key symptom of frontotemporal dementia (FTD) is difficulty interacting socially with others. Social cognition problems in FTD include impaired emotion processing and theory of mind difficulties, and whilst these have been studied extensively in sporadic FTD, few studies have investigated them in familial FTD. Facial Emotion Recognition (FER) and Faux Pas (FP) recognition tests were used to study social cognition within the Genetic Frontotemporal Dementia Initiative (GENFI), a large familial FTD cohort of C9orf72, GRN, and MAPT mutation carriers. 627 participants undertook at least one of the tasks, and were separated into mutation-negative healthy controls, presymptomatic mutation carriers (split into early and late groups) and symptomatic mutation carriers. Groups were compared using a linear regression model with bootstrapping, adjusting for age, sex, education, and for the FP recognition test, language. Neural correlates of social cognition deficits were explored using a voxel-based morphometry (VBM) study. All three of the symptomatic genetic groups were impaired on both tasks with no significant difference between them. However, prior to onset, only the late presymptomatic C9orf72 mutation carriers on the FER test were impaired compared to the control group, with a subanalysis showing differences particularly in fear and sadness. The VBM analysis revealed that impaired social cognition was mainly associated with a left hemisphere predominant network of regions involving particularly the striatum, orbitofrontal cortex and insula, and to a lesser extent the inferomedial temporal lobe and other areas of the frontal lobe. In conclusion, theory of mind and emotion processing abilities are impaired in familial FTD, with early changes occurring prior to symptom onset in C9orf72 presymptomatic mutation carriers. Future work should investigate how performance changes over time, in order to gain a clearer insight into social cognitive impairment over the course of the disease.
Original languageEnglish
Pages (from-to)384-398
Number of pages15
JournalCortex
Volume133
DOIs
Publication statusPublished - 1 Dec 2020

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