A comparison of the cognitive and behavioural characteristics of frontotemporal dementia with and without accompanying amyotrophic lateral sclerosis

Abstract

Around 15% of people with frontotemporal dementia (FTD) develop amyotrophic lateral sclerosis (ALS). Research in ALS has highlighted clinical features akin to those described in FTD. Nevertheless, it is not known whether the neuropsychological profiles of ALS-FTD and FTD are indistinguishable and there have been few direct comparisons of the two conditions. This thesis aims to improve understanding of the relationship between ALS-FTD and FTD through direct comparison of the cognitive and behavioural characteristics of FTD with and without accompanying ALS. The experimental work consists of both retrospective and prospective studies. The retrospective work begins by examining the subtypes of FTD most commonly diagnosed alongside ALS. The second retrospective study identifies the cognitive, behavioural and neuropsychiatric features reported in behavioural variant FTD (bvFTD) and ALS-FTD. A detailed cross-sectional prospective study then interrogates features of executive function, social cognition, language and behaviour through neuropsychological testing and caregiver reports. Genetic influences are also explored. A closer examination of the qualitative aspects of language performance follows, exploring the basis for impairments in sentence ordering and spelling. The examination of FTD subtypes found that bvFTD was by far the most common subtype alongside ALS. Pure language syndromes of semantic dementia and progressive aphasia were rare. Despite this, mixed language/behavioural syndromes occurred at a comparable rate in both FTD and ALS-FTD, suggesting that language features do occur in ALS but are most common in the context of a behavioural syndrome. The second retrospective study found that the bvFTD group demonstrated more behavioural change and were more likely than the ALS-FTD group to show social disinhibition, dietary change and repetitive behaviour. Some features, such as apathy, were common in both groups. Conversely, the ALS-FTD group showed greater impairment in grammar production and sentence comprehension. The prospective study found that the bvFTD group showed more behavioural change on average and greater disinhibition, dietary change, repetitive behaviours and changes in sympathy/empathy than the ALS-FTD group. The presence of apathy was equally common across groups, but the bvFTD group elicited higher scores on a measure that also addressed severity. The ALS-FTD group showed poorer verbal fluency than did the bvFTD group. Contrary to expectations, few significant group differences were found in terms of language profiles, although ALS-FTD group scores were numerically lower on a test of sentence ordering. Examination of the data showed significant variability in the groups. Additionally, the presence of the hexanucleotide repeat expansion on C9ORF72 was linked to language impairment in both diagnostic groups. A close examination of the data for sentence ordering and qualitative examination of spelling errors revealed a complex picture in which both language and executive impairments appeared to contribute to impaired performance. However, there was evidence of genuine language dysfunction in a subset of ALS-FTD patients, while impairments in bvFTD may be primarily mediated by executive dysfunction. The data demonstrate significant overlap between the groups and heterogeneity within them, mediated in part by genetic contributions. Nevertheless, the findings indicate key differences in the behavioural profiles of ALS-FTD and bvFTD, with a suggestion of greater language impairment in ALS-FTD. The findings are relevant for clinical assessment and have theoretical implications for the idea of a single spectrum of disease.

Date of Award	31 Dec 2018
Original language	English
Awarding Institution	The University of Manchester
Supervisor	Matthew Jones (Supervisor), Jennifer Thompson (Supervisor) & Julie Snowden (Supervisor)