Anomia is present pre-symptomatically in frontotemporal dementia due to MAPT mutations
Authors: Bouzigues Arabella , Russell Lucy L. , Peakman Georgia , Bocchetta Martina , Greaves Caroline V. , Convery Rhian S. , Todd Emily , Rowe James B. , Borroni Barbara , Galimberti Daniela , Tiraboschi Pietro , Masellis Mario , Tartaglia Maria Carmela , Finger Elizabeth , van Swieten John C. , Seelaar Harro , Jiskoot Lize , Sorbi Sandro , Butler Chris R. , Graff Caroline , Gerhard Alexander , Langheinrich Tobias , Laforce Robert , Sanchez-Valle Raquel , de Mendonça Alexandre , Moreno Fermin , Synofzik Matthis , Vandenberghe Rik , Ducharme Simon , Le Ber Isabelle , Levin Johannes , Danek Adrian , Otto Markus , Pasquier Florence , Santana Isabel , Rohrer Jonathan D. ,   The Genetic FTD Initiative, GENFI, Esteve Aitana Sogorb , Nelson Annabel , Bouzigues Arabella , Heller Carolin , Greaves Caroline V , Cash David , Thomas David L , Todd Emily , Benotmane Hanya , Zetterberg Henrik , Swift Imogen J , Nicholas Jennifer , Samra Kiran , Russell Lucy L , Bocchetta Martina , Shafei Rachelle , Convery Rhian S , Timberlake Carolyn , Cope Thomas , Rittman Timothy , Benussi Alberto , Premi Enrico , Gasparotti Roberto , Archetti Silvana , Gazzina Stefano , Cantoni Valentina , Arighi Andrea , Fenoglio Chiara , Scarpini Elio , Fumagalli Giorgio , Borracci Vittoria , Rossi Giacomina , Giaccone Giorgio , Caroppo Paola , Tiraboschi Pietro , Prioni Sara , Redaelli Veronica , Tang-Wai David , Rogaeva Ekaterina , Castelo-Branco Miguel , Keren Ron , Black Sandra , Mitchell Sara , Shoesmith Christen , Bartha Robart , Rademakers Rosa , Poos Jackie , Papma Janne M , Giannini Lucia , Minkelen Rick , Pijnenburg Yolande , Nacmias Benedetta , Ferrari Camilla , Polito Cristina , Lombardi Gemma , Bessi Valentina , Veldsman Michele , Andersson Christin , Thonberg Hakan , Öijerstedt Linn , Jelic Vesna , Thompson Paul , Langheinrich Tobias , Lladó Albert , Antonell Anna , Olives Jaume , Balasa Mircea , Bargalló Nuria , Borrego-Ecija Sergi , Verdelho Ana , Maruta Carolina , Ferreira Catarina B , Miltenberger Gabriel , do Couto Frederico Simões , Gabilondo Alazne , Gorostidi Ana , Villanua Jorge , Cañada Marta , Tainta Mikel , Zulaica Miren , Barandiaran Myriam , Alves Patricia , Bender Benjamin , Wilke Carlo , Graf Lisa , Vogels Annick , Vandenbulcke Mathieu , Van Damme Philip , Bruffaerts Rose , Poesen Koen , Rosa-Neto Pedro , Gauthier Serge , Camuzat Agnès , Brice Alexis , Bertrand Anne , Funkiewiez Aurélie , Rinaldi Daisy , Saracino Dario , Colliot Olivier , Sayah Sabrina , Prix Catharina , Wlasich Elisabeth , Wagemann Olivia , Loosli Sandra , Schönecker Sonja , Hoegen Tobias , Lombardi Jolina , Anderl-Straub Sarah , Rollin Adeline , Kuchcinski Gregory , Bertoux Maxime , Lebouvier Thibaud , Deramecourt Vincent , Santiago Beatriz , Duro Diana , Leitão Maria João , Almeida Maria Rosario , Tábuas-Pereira Miguel , Afonso Sónia , Engel Annerose , Polyakova Maryna 
Published: March 2022

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.