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Title: Language impairment in neurodegenerative disease : a clinical, neuropsychological and neuroimaging study
Author: Harris, Jennifer
ISNI:       0000 0001 1471 4395
Awarding Body: University of Manchester
Current Institution: University of Manchester
Date of Award: 2016
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Accurate diagnosis of dementia syndromes can be challenging, particularly neurodegenerative disorders of language, or primary progressive aphasias (PPAs). PPAs are heterogeneous clinical and pathological entities. The two main pathological causes of PPA are frontotemporal lobar degeneration (FTLD) and Alzheimer's disease (AD). PPA is associated with other neurodegenerative disorders owing to common underlying pathologies, in particular behavioural variant frontotemporal dementia (bvFTD) and semantic dementia (SD), other FTLD disorders, and non-language presentations of AD. The aim of this thesis is to improve understanding of PPA and associated disorders, with the eventual goal of improving diagnostic accuracy and clinical management of PPA. The experimental section falls into two parts. In the first the clinical features of a large pathological cohort were rated against clinical criteria for PPA, AD and bvFTD. The degree to which patients with underlying FTLD pathology exhibit overlapping behavioural and language deficits was also assessed. The second part of the experimental section is a series of prospective studies of patients with clinically diagnosed PPA, SD and AD. These studies involve detailed cross-sectional cognitive assessment, predominantly of language and working memory, and neuroimaging investigations. The retrospective studies revealed that it was not possible to classify all cases of PPA and that pathologies were heterogeneous within PPA subtypes, particularly for logopenic variant PPA (lvPPA). Clinical criteria for bvFTD and AD were found to be relatively effective. Overlapping language and behavioural symptoms were found to be common in FTLD. The prospective studies demonstrated characteristic linguistic features of nonfluent variant PPA (nfvPPA) and SD. In addition, behavioural changes were common in nfvPPA and SD. The lvPPA group did not exhibit significant impairments in language and working memory in comparison to nfvPPA and AD groups. Indeed, some features included in criteria for lvPPA occurred more frequently in nfvPPA. Nevertheless discrete factors representing 'speech production and grammaticality' and 'visual working memory and calculation' were able to differentiate nfvPPA and lvPPA effectively. There were commonalities between AD and lvPPA, and the composite measures described above did not allow effective classification of patients with these two disorders. Neuroimaging metrics showed that overlapping yet slightly differing patterns of changes in grey matter, cerebral blood flow and white matter connections occur in lvPPA and nfvPPA.Current criteria for PPA are ineffective. This is particularly apparent for lvPPA whereby core features are not specific or sensitive to lvPPA. It is evident that commonalities exist between FTLD disorders i.e. nfvPPA, semantic variant PPA and bvFTD, and between AD and lvPPA. These features may aid clinical diagnosis.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available