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


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Abstract

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.

Description

Funder: Alzheimer’s Research UK; doi: http://dx.doi.org/10.13039/501100002283


Funder: UCLH Biomedical Research Centre; doi: http://dx.doi.org/10.13039/501100012317


Funder: Medical Research Council; doi: http://dx.doi.org/10.13039/501100000265


Funder: Leonard Wolfson Experimental Neurology Centre (LWENC) Clinical Research Facility


Funder: Bluefield Project

Keywords
C9orf72, Cognition, Frontotemporal dementia, Naming, Progranulin, Tau, Anomia, C9orf72 Protein, Frontotemporal Dementia, Humans, Mutation, Progranulins, tau Proteins
Journal Title
J Neurol
Conference Name
Journal ISSN
0340-5354
1432-1459
Volume Title
269
Publisher
Springer Science and Business Media LLC
Sponsorship
National Institute for Health and Care Research (IS-BRC-1215-20014)