Anomia is present pre-symptomatically in frontotemporal dementia due to MAPT mutations.

Content Provider	Europe PMC
Author	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.
Abstract	IntroductionA 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.MethodsWe 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.ResultsAll 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.ConclusionThis 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.Supplementary InformationThe online version contains supplementary material available at 10.1007/s00415-022-11068-0.
ISSN	03405354
Journal	Journal of Neurology
Volume Number	269
PubMed Central reference number	PMC9294015
Issue Number	8
PubMed reference number	35348856
e-ISSN	14321459
DOI	10.1007/s00415-022-11068-0
Language	English
Publisher	Springer Berlin Heidelberg
Publisher Date	2022-03-29
Publisher Place	Berlin/Heidelberg
Access Restriction	Open
Rights License	Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. © The Author(s) 2022
Subject Keyword	Frontotemporal dementia Tau Progranulin C9orf72 Naming Cognition
Content Type	Text
Resource Type	Article
Subject	Neurology Neurology (clinical)