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.

Clinical and neuroimaging characterization of the first frontotemporal dementia family carrying the MAPT p.K298E mutation

“…Analogously, non-fluent aphasia phenotypes have been described with exon 10 MAPT mutations [ 15 ]. In a GENFI study, 80% of MAPT -related FTD exhibited language impairment, with various patterns [ 16 ], and naming performances were the worst among genetic FTD forms. Correlates of anomia in MAPT mutation carriers were found in the anterior temporal lobes and anterior insula [ 17 ].…”

“…Indeed, MAPT mutations affecting exon 10 splicing seem to be predominantly associated with structural and metabolic medial temporal lobe involvement [ 8 ]. In the aforementioned GENFI cohort, the temporal pole was atrophic in up to 70% of MAPT mutation carriers, significantly differing from other mutation groups [ 16 ]. Temporal lobe volumes show the fastest decline over time even in presymptomatic MAPT mutation carriers [ 26 ], and it was even more accelerated in those who converted to dementia, who also showed frontal and parietal longitudinal atrophy [ 27 ].…”

Pharmacogenomics of Dementia: Personalizing the Treatment of Cognitive and Neuropsychiatric Symptoms

“…Some patients may exhibit repetitive or compulsive motor actions or develop unconventional eating habits [18], leading to potential misdiagnoses, such as major depressive or bipolar disorder. Apart from the behavioral variant, there are three language variants in FTD: the semantic variant, characterized by difficulties in naming and comprehending words; nonfluent aphasia, characterized by the challenges related to speech and/or grammar apraxia; and the logopenic subtype, characterized by issues with word retrieval [32].…”

A Systematic Review of the Quantitative markers of speech and language of the Frontotemporal Degeneration Spectrum and their potential for cross-linguistic implementation

“…All variants of primary progressive aphasia (PPA) by definition present with prominent abnormalities of speech and/or language (Gorno-Tempini et al, 2011), but the FTD spectrum as a whole is strongly associated with such impairments. In behavioral variant FTD (bvFTD), word retrieval, comprehension, reading, writing, verbal and non-verbal semantic knowledge, as well as prosody of speech are impaired, while motor speech and repetition abilities remain generally conserved (Geraudie et al, 2021; Samra et al, 2023). On the other side of the spectrum, progressive supranuclear palsy (PSP) and corticobasal syndrome (CBS) have been more often associated with motor speech impairments such as apraxia of speech and dysarthria, though more recent research also shows impairment in language abilities, such as confrontation naming, fluency, sentence comprehension and production (Peterson et al, 2019).…”