Language impairment in the genetic forms of behavioural variant frontotemporal dementia

Abstract

Background: Behavioural variant fronto-temporal dementia (bvFTD) is characterised by a progressive change in personality in association with atrophy of the frontal and temporal lobes. Whilst language impairment has been described in people with bvFTD, little is currently known about the extent or type of linguistic difficulties that occur, particularly in the genetic forms.

Methods: Participants with genetic bvFTD along with healthy controls were recruited from the international multicentre Genetic FTD Initiative (GENFI). Linguistic symptoms were assessed using items from the Progressive Aphasia Severity Scale (PASS). Additionally, participants undertook the Boston Naming Test (BNT), modified Camel and Cactus Test (mCCT) and a category fluency test. Participants underwent a 3T volumetric T1-weighted MRI, with language network regional brain volumes measured and compared between the genetic groups and controls.

Results: 76% of the genetic bvFTD cohort had impairment in at least one language symptom: 83% C9orf72, 80% MAPT and 56% GRN mutation carriers. All three genetic groups had significantly impaired functional communication, decreased fluency, and impaired sentence comprehension. C9orf72 mutation carriers also had significantly impaired articulation and word retrieval as well as dysgraphia whilst the MAPT mutation group also had impaired word retrieval and single word comprehension. All three groups had difficulties with naming, semantic knowledge and verbal fluency. Atrophy in key left perisylvian language regions differed between the groups, with generalised involvement in the C9orf72 group and more focal temporal and insula involvement in the other groups. Correlates of language symptoms and test scores also differed between the groups.

Conclusions: Language deficits exist in a substantial proportion of people with familial bvFTD across all three genetic groups. Significant atrophy is seen in the dominant perisylvian language areas and correlates with language impairments within each of the genetic groups. Improved understanding of the language phenotype in the main genetic bvFTD subtypes will be helpful in future studies, particularly in clinical trials where accurate stratification and monitoring of disease progression is required.

Keywords: C9orf72; Frontotemporal dementia; Genetics; Language; Progranulin; Tau.

Fig. 1

a Left perisylvian regions included in the MR imaging analysis are shown in this artificial representation of the lateral surface of the brain, with the insula and supratemporal region shown in darker blue to represent that they are deeper structures within the sylvian fissure, and b region of interest volumes in each genetic group as a percentage of mean control volume: IFG inferior frontal gyrus; INS insula; MOT motor cortex; TP temporal pole; STG superior temporal gyrus; STR supratemporal region; ANG angular gyrus. The darkest colours represent areas of lowest brain volume as per the key

Fig. 2

The percentage of participants in each of the groups who score 0 = absent, 0.5 = very mild/questionable, 1 = mild, 2 = moderate, or 3 = severe for each linguistic symptom. Values along the x-axis represent the frequency (%) with which the symptom is present in any severity category (0.5–3). An asterisk above the bar indicates that the symptom severity is significantly greater than controls

Fig. 3

The percentage of participants with a particular number of language symptoms present, including all mutation carriers and each of the mutation groups