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Title: Lexical-semantic parameters as robust endophenotypes of abnormal cognitive decline in ageing
Author: Biundo, Roberta
ISNI:       0000 0004 2722 7395
Awarding Body: University of Hull
Current Institution: University of Hull
Date of Award: 2010
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The objective of this dissertation was to characterise the relative contribution of genetic influences to individual differences in cross sectional performance and decline of semantic-lexical abilities and to investigate whether these linguistic effects indicating semantic degradation are sensitive indicators of medial temporal atrophy in early Alzheimer's disease and in patients with mild cognitive impairment of amnestic type (aMCI). The effect of ApoE status in the genetic profile of these groups on deterioration of semantic abilities was studied to verify whether there was any relationship between variation in lexical factors and genetic variability. Oral generation of words belonging to two categories (animal and fruits) during a fluency tasks was required. In AD patients there was an effect of genotype but, although strong, this was diluted by the advanced cognitive deterioration and could only be seen as a tendency to be stronger in ε4 carriers. The words produced by the aMCI carriers were significantly earlier acquired than those of non-carriers and controls. These behavioural findings confirmed evidence from other recent studies and showed that a significant proportion of phenotype variability in performance on fluency tasks was influenced by genetic factors. Impairments in semantic tasks in the ε4 allele carrier population might indicate either that individuals who will develop AD never fully develop semantic skills, or that the neuroanatomical substrate of semantic abilities is selective sensitive to the earliest effects of the AD neuropathology. On the basis of this result it seemed reasonable to hypothesise that the presence of the “semantic endophenotype” in people carriyng the ApoE vulnerability mutation might be associated with atrophy in areas early affected by neuropathology due to AD and involved in semantic memory retrieval. Using lexical semantic competency in aMCI carriers as an endophenotype, grey matter volume loss in aMCI ε4 carriers/non-carriers and in controls was compared and the residual volume correlated with allele burden and with age of acquisition values for words produced in a category fluency task. Direct group comparisons showed that carriers had grey matter volume loss which was generally confined to limbic regions and medial temporal structures, and non-carriers had greater atrophy in temporal and parieto-occipital neocortex. aMCI subjects had significantly impoverished lexical semantic output compared to controls, more marked in aMCI carriers. A voxel based correlation analysis showed that greater volume loss in parahippocampal gyrus and thalamus was associated with a tendency to retrieve earlier acquired words in the category fluency task. The results suggest a relatively specific impact of ApoE 4 burden and underline the value of linguistic assessment in preclinical diagnosis. The detrimental role of this mutation found in aMCI individuals was also assessed at the larger stage in the disease process by direct comparisons in minimal to mild AD ε4 carriers/non-carrier patients. VBM comparison analysis confirmed the observation done in the genetically determined aMCI subgroups. AD ε4- carriers showed greater atrophy in mediotemporal structures compared to non-carriers whose grey matter volume loss was more widespread in more neocortical areas. Finally, an age, gender and education based norms for AoA, Typicality and Familiarity was built up in order to create a valid psychometric instrument able to detect and monitor subtle semantic deficits in ApoE ε4 carriers over time.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available
Keywords: Psychology