Arabella Bouzigues, UCL Queen Square Institute of Neurology
Lucy L. Russell, UCL Queen Square Institute of Neurology
Georgia Peakman, UCL Queen Square Institute of Neurology
Martina Bocchetta, UCL Queen Square Institute of Neurology
Caroline V. Greaves, UCL Queen Square Institute of Neurology
Rhian S. Convery, UCL Queen Square Institute of Neurology
Emily Todd, UCL Queen Square Institute of Neurology
James B. Rowe, Cambridge University Hospitals NHS Foundation Trust
Barbara Borroni, Università degli Studi di Brescia
Daniela Galimberti, Università degli Studi di Milano
Pietro Tiraboschi, Foundation IRCCS Neurological Institute "C. Besta"
Mario Masellis, University of Toronto
Maria Carmela Tartaglia, Tanz Centre for Research in Neurodegenerative Diseases
Elizabeth Finger, Western UniversityFollow
John C. van Swieten, Erasmus MC
Harro Seelaar, Erasmus MC
Lize Jiskoot, Erasmus MC
Sandro Sorbi, Università degli Studi di Firenze
Chris R. Butler, University of Oxford Medical Sciences Division
Caroline Graff, Karolinska Institutet
Alexander Gerhard, The University of Manchester
Tobias Langheinrich, The University of Manchester
Robert Laforce, CHU de Québec - Université Laval
Raquel Sanchez-Valle, Universitat de Barcelona
Alexandre de Mendonça, Faculdade de Medicina, Universidade de Lisboa
Fermin Moreno, Osakidetza, Donostia University Hospital
Matthis Synofzik, Hertie-Institut für klinische Hirnforschung
Rik Vandenberghe, Departement Neurowetenschappen
Simon Ducharme, School of Medicine
Isabelle Le Ber, Sorbonne Universite

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Journal of neurology





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INTRODUCTION: A third of frontotemporal dementia (FTD) is caused by an autosomal-dominant genetic mutation in one of three genes: microtubule-associated protein tau (MAPT), chromosome 9 open reading frame 72 (C9orf72) and progranulin (GRN). Prior studies of prodromal FTD have identified impaired executive function and social cognition early in the disease but few have studied naming in detail. METHODS: We investigated performance on the Boston Naming Test (BNT) in the GENetic Frontotemporal dementia Initiative cohort of 499 mutation carriers and 248 mutation-negative controls divided across three genetic groups: C9orf72, MAPT and GRN. Mutation carriers were further divided into 3 groups according to their global CDR plus NACC FTLD score: 0 (asymptomatic), 0.5 (prodromal) and 1 + (fully symptomatic). Groups were compared using a bootstrapped linear regression model, adjusting for age, sex, language and education. Finally, we identified neural correlates of anomia within carriers of each genetic group using a voxel-based morphometry analysis. RESULTS: All symptomatic groups performed worse on the BNT than controls with the MAPT symptomatic group scoring the worst. Furthermore, MAPT asymptomatic and prodromal groups performed significantly worse than controls. Correlates of anomia in MAPT mutation carriers included bilateral anterior temporal lobe regions and the anterior insula. Similar bilateral anterior temporal lobe involvement was seen in C9orf72 mutation carriers as well as more widespread left frontal atrophy. In GRN mutation carriers, neural correlates were limited to the left hemisphere, and involved frontal, temporal, insula and striatal regions. CONCLUSION: This study suggests the development of early anomia in MAPT mutation carriers, likely to be associated with impaired semantic knowledge. Clinical trials focused on the prodromal period within individuals with MAPT mutations should use language tasks, such as the BNT for patient stratification and as outcome measures.