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Background: Semantic dementia occurs as part of the frontotemporal dementia spectrum of conditions and presents with a progressive and striking receptive and expressive communication disorder. Studies thus far have generally concentrated on quantitative assessment of cognition and behaviour and there is a paucity of research examining conversation skills in everyday life, despite people with this condition and their family carers identifying this as the primary focus of their difficulties. There is also a gap in the literature in examining the first-hand experiences of people with semantic dementia and their family carers, in terms of how they live day to day with this condition. There is currently no evidence based advice for management of everyday communication issues in semantic dementia. Aims: This thesis used a multiple case study design to explore everyday conversation at home with five individuals with semantic dementia and their spouses and in one case study, also a daughter. Individuals ranged from early semantic dementia to the advanced stages of this condition. Each case study used an innovative combination of conversation analysis of video and audio data alongside biographical interviewing in a longitudinal design. A total of 74 home visits gathered 45 hours of interview data and 12 hours of video data. Information derived from these strands was then used to design an individually tailored intervention which focussed on the specific everyday conversation issues in each situation. This included aspects of life story work and interaction-focused therapy. Findings: A range of challenges and skills were present in the everyday conversations of these individuals with semantic dementia and their family carers. Some of this variability arose from differences in the severity of the semantic dementia across individuals in the study. However, differences were also apparent in how individuals with semantic dementia and their family carers adapted to the condition. Interaction-focussed therapy was delivered in one case study, with measureable changes in post-therapy conversations at home. Life story work was delivered in all cases using a variety of formats. Analysis of outcomes highlighted that the work could be conceptualised under various points of connection: including interactional connections, emotional connections, building new connections, practical care connections and future connections. Cognitive, psychological and social factors impacted on the life story work. Creativity in practice was important to enhance not just information exchange but foster interaction using verbal, paralinguistic and embodied behaviours. Conclusion: The study contributes to knowledge by providing in-depth understanding of the changes in everyday conversation for those living with semantic dementia and their family carers, as well as exploring interventions directly relevant for clinical practice. In this study both interaction-focussed therapy and life story work offered promise to support and enhance adaptation to changes in interaction for all concerned. Aspects of both interventions, grounded in the study data, were proposed in an exploratory model to underpin ‘interaction-focussed life story work’ in semantic dementia, i.e. life story practice with a central aim to enhance strategies for interaction in everyday life.

This thesis investigated the role of the anterior temporal lobes (ATLs) in conceptual knowledge and name relearning by studying people with semantic dementia (SD). People with SD have atrophy focussed on the ATLs and they exhibit a pan-modal semantic impairment (e.g., Hodges, Patterson, Oxbury, & Funnell, 1992). Recent evidence suggests that modality-invariant concept representations are built up in the ATLs and that these modality-invariant representations are crucial for abstracting away from the surface features of items in order to generalise conceptual information based on their core semantic similarity (e.g., Lambon Ralph & Patterson, 2008). In order to test this, two of the studies described in this thesis (Chapters 2 and 3) assessed semantic generalisation in people with SD. These studies showed that people with SD are less able to generalise conceptual information on the basis of the deeper semantic structure of concepts but instead are increasingly influenced by the superficial similarity of the items. These studies support the hypothesis that the modality-invariant representations formed in the ATLs are crucial for semantic-based generalisation. Previous SD relearning studies have reported relatively good learning but a lack of generalisation to untrained items, tasks, and/or contexts (i.e., under-generalisation). This has been interpreted based on the Complementary Learning Systems (CLS) (McClelland, McNaughton, & O'Reilly, 1995) to suggest that the neocortical semantic system no longer makes a meaningful contribution to relearning but instead relearning is primarily dependent upon the sparse representational medial temporal lobe (MTL) learning system. The studies described in two of the thesis chapters (Chapters 4 and 5) investigated the role of the underlying systems further and found that the neocortical semantic system does still contribute to relearning in SD (although its contribution is disordered and based on the degraded concept representations in the ATL) but there is a shift in the division of labour such that the MTL system takes over more of the work. Finally, in order to clarify the outcomes of relearning in SD, Chapter 6 reviewed all of the previous SD relearning studies and confirmed that people with SD are able to relearn the specific information that they study but that this relearning is rigid. The review and a subsequent re-analysis of the data from Chapters 4 and 5 also showed that relearning in SD can have negative side-effects as well as positive effects.

Στην παρούσα εργασία αξιολογείται η σημασιολογική γνώση ατόμων που νοσούν από Σημασιολογική Άνοια, στο πλαίσιο της διαφοροποίησης στην κατανόηση και επεξεργασία ανάμεσα στις συγκεκριμένες και αφηρημένες έννοιες. Η αξιολόγηση πραγματοποιείται με τη δοκιμασία λεξικής απόφασης με προέγερση, βασισμένη στη σχέση ομοιότητας(συνωνυμία) που χαρακτηρίζει τα ερεθίσματα. Τα αποτελέσματα της δοκιμασίας διαμορφώνονται από το χρόνο αντίδρασης των συμμετεχόντων και το ποσό διευκόλυνσης που τους παρέχουν οι προεγέρτες και στη συνέχεια παρουσιάζονται γραφηματικά και ερμηνεύονται. / In the particular project we assess the semantic knowledge of people with Semantic Dementia,under the differentiation in understanding and processing between concrete and abstract concepts. The assessment is performed with the linguistic experiment of lexical decision with priming, based on the similarity relation that characterises the stimuli. The experiment's results are formed by the participants' reaction time and the amount of priming which is offered by the lexical primes and therefore the results are presented in a graph and they are interpreted.

La cognition sociale fait référence à un ensemble de processus cognitifs fonctionnant en interaction permettant de se comporter de manière adaptée dans le monde social. La théorie de l’esprit (TDE) est considérée comme étant l’élément central de la cognition sociale, mais les liens entre les processus sont encore mal connus. Les capacités de TDE se manifestent au quotidien au travers des relations interpersonnelles, mais l’effet du contexte sur la TDE demeure encore mal connu. L’objectif principal de ce travail de thèse consistait à étudier conjointement la TDE et les connaissances sociales ainsi que les liens existant entre ces deux dimensions. Nous résultats mettent en évidence que les capacités à attribuer des états mentaux sont modulées par le contexte et plus précisément par l’intégrité des connaissances sociales dans la maladie d’Alzheimer et dans la démence sémantique. Les troubles des patients pourraient avoir une origine différente, en lien avec l’atteinte cérébrale. La cognition sociale pourrait ainsi être un élément utile dans le cadre du diagnostic différentiel des maladies neurodégénératives. / Social cognition refers to a set of processes working interactively that allows to behave appropriately in the social world. Theory of mind (TOM) is considered to be the central element of social cognition, but the links between its different processes are still poorly understood. TOM’s abilities are used daily through interpersonal relationships, but the effect of the context on TOM remains poorly explored. The main aim of this thesis was to study both TOM and social knowledge, as well as the links between them. Our results highlight how the ability to attribute mental states is modulated by the context and more specifically by the integrity of social knowledge in Alzheimer's disease and semantic dementia. Patients’ disorders may have a different origin depending on their brain lesions. Therefore, social cognition could be a useful element in the differential diagnosis for neurodegenerative diseases.

L’augmentation de la prévalence des démences est un problème majeur d’intérêt international. À la différence du vieillissement normal, la démence désigne l’affaiblissement progressif de l’ensemble des fonctions intellectuelles : mémoire, attention, jugement, capacité de raisonnement et les perturbations de conduite qui en résultent. Mondialement, on estime que 35,6 millions de personnes sont atteintes de démence et on dénombre 7,7 millions de nouveaux cas chaque année (WHO, 2012). Dans ce contexte, la détection précoce, prédiction et dissociation des différents syndromes démentiels sont d’un intérêt primordial, en particulier à des fins de traitement. Au cours de la dernière décennie, la littérature scientifique a montré, grâce à l’apport des outils de neuroimagerie, une association entre les troubles de la mémoire épisodique observés chez les patients atteints de maladie d’Alzheimer (MA) et l’atrophie hippocampique qu’on retrouve également chez la majorité d’entre eux (Petersen et al., 2000). Toutefois, plusieurs études portant sur la variante sémantique de l’aphasie primaire progressive (vsAPP), anciennement appelée la démence sémantique (Gorno-Tempini et al., 2011), retrouvent un patron d’atrophie semblable à celui retrouvé dans la MA en ce qui concerne l’hippocampe (Chan et al., 2001; Davies, Graham, Xuereb, Williams, & Hodges, 2004; Duval et al., 2012; Galton et al., 2001; Gorno-Tempini et al., 2004; Hornberger & Piguet, 2012; Nestor, Fryer, & Hodges, 2006; Pleizier et al., 2012; Schroeter & Neumann, 2011). Or, au niveau cognitif, ces patients démontrent plutôt une détérioration de la mémoire sémantique et n’ont généralement pas de trouble majeur au niveau de la mémoire épisodique, du moins durant les premières phases de la maladie (Gorno-Tempini et al., 2011). Il s’avère donc primordial de comparer et de préciser nos connaissances par rapport à l’implication de l’hippocampe dans ces deux pathologies afin d’orienter leurs diagnostics cliniques respectifs et de mieux diriger les méthodes d’intervention disponibles. Une étude récente a montré, chez des participants en santé, que des parties différentes de l’hippocampe sont impliquées dans le réseau de la mémoire épisodique comparativement à celui de la mémoire sémantique (La Joie et al., 2014). La partie antérieure de l’hippocampe serait impliquée dans la mémoire sémantique, tandis que la partie postérieure de cette structure serait plutôt associée à la mémoire épisodique. Notre hypothèse générale est donc que des parties différentes de l’hippocampe sont touchées dans les deux maladies en raison de leurs connexions distinctes avec les deux systèmes soutenant la mémoire épisodique et sémantique respectivement, et qu’ainsi la partie antérieure de l’hippocampe est plus touchée dans la vsAPP et la partie postérieure est plus touchée dans la MA. Le premier article de la thèse visait à identifier et comparer le patron d’atrophie cérébrale associé à la vsAPP et la MA à travers une méta-analyse basée sur des études anatomiques antérieures, et à caractériser plus précisément le volume de l’hippocampe sous un axe antéro-postérieur dans les deux maladies. Les résultats de l’étude ont confirmé la signature d’atrophie cérébrale classique observée dans les deux maladies, mais également l’hypothèse que l’hippocampe est touché de façon bilatérale dans la MA et la vsAPP. Par contre, dans la vsAPP, l’atrophie est limitée à la partie antérieure de la structure tandis qu’une atrophie plus globale a été observée dans la MA. De plus, lorsque les deux groupes ont été directement comparés, une atrophie plus prononcée de la partie postérieure a été observée dans le groupe MA versus vsAPP. Le deuxième article de la thèse visait à investiguer l’effet de la vsAPP sur les patrons de connectivité fonctionnelle de l’hippocampe antérieur versus postérieur. Les résultats ont montré deux patrons différents de connectivité fonctionnelle, entre l’hippocampe antérieur versus postérieur et le reste du cerveau, chez les contrôles. De plus, une réduction de la connectivité dans l’hippocampe antérieur a été observée chez le groupe vsAPP, et une connectivité fonctionnelle comparable à celle des contrôles a été trouvée dans l’hippocampe postérieur. Globalement, nos résultats confirment que l’atrophie de l’hippocampe est présente, mais de façon différentielle, dans la MA et la vsAPP. Nos résultats soutiennent également l’hypothèse que les syndromes neurodégénératifs comme la MA et la vsAPP n’impliquent pas seulement des atrophies focales, mais découlent plutôt d’une déconnexion entre diverses régions anatomiques, et que les symptômes cliniques sont causés par cette scission dans les réseaux neuronaux qui supportent des fonctions cognitives comme la mémoire sémantique et épisodique. / The increase in the prevalence of dementia is a major international concern. Unlike normal aging, dementia refers to the progressive weakening of all intellectual functions: memory, attention, judgment, reasoning ability, and the resulting behavioral changes. Globally, it is estimated that 35.6 million people are affected by dementia, and 7.7 million of new cases are reported each year (WHO, 2012). In this context, early detection, prediction and dissociation of these different syndromes are of primary interest, particularly for treatment purposes. Over the past decade, the scientific literature has shown, with the help of neuroimaging tools, an association between the episodic memory impairments observed in patients with Alzheimer's disease (AD) and the hippocampal atrophy found in the majority of these patients (Petersen et al., 2000). However, several studies regarding the semantic variant of primary progressive aphasia (svPPA), previously known as semantic dementia (Gorno- Tempini et al., 2011), find a similar hippocampal atrophy pattern to that found in AD patients (Brambati et al., 2009; Chan et al., 2001; Davies et al., 2004; Desgranges et al., 2007; Galton et al., 2001; Nestor et al., 2006). However, from a cognitive perspective, these patients rather demonstrate a deterioration of semantic memory and do not generally show episodic memory impairments, at least during the beginning of the disease (Gorno-Tempini et al., 2011). It is therefore essential to compare and clarify our knowledge regarding the involvement of the hippocampus in these two pathologies in order to guide their respective clinical diagnoses and available intervention methods. A recent study has shown, in healthy participants, that different parts of the hippocampus are involved in the episodic versus semantic memory networks (La Joie et al., 2014). The anterior part of the hippocampus would be involved in semantic memory, whereas the posterior part of this structure would be associated to episodic memory. Our general hypothesis is that different parts of the hippocampus are affected in both diseases, because of their distinct connections to the two systems supporting episodic and semantic memory, and thus that the anterior part of the hippocampus would be impaired in svPPA whereas the posterior part would be impaired in AD. The first article of the thesis aimed to identify and compare the pattern of cerebral atrophy associated with svPPA and AD through a meta-analysis based on previous anatomical studies, and to further characterize the volume of the hippocampus under an antero-posterior axis in both diseases. The results of the study confirmed the hypothesis that, in addition to the classical signature of cerebral atrophy observed in both diseases, the hippocampus is affected bilaterally in AD and svPPA. In svPPA, however, the atrophy is limited to the anterior part of the structure whereas a more general atrophy was observed in AD. In addition, when both groups were directly compared, a more pronounced posterior atrophy was observed in the AD versus svPPA group. The second article of the thesis aimed to investigate the impact of AD and svPPA on the functional connectivity patterns of the anterior versus posterior hippocampus. The results showed two different patterns of functional connectivity, between the anterior and posterior hippocampus and the rest of the brain, in controls. A reduction in functional connectivity in the anterior hippocampus was observed in svPPA, whereas a comparable functional connectivity pattern to that of controls was observed in the posterior hippocampus. Overall, our results confirm that atrophy of the hippocampus is present, but affects different parts of the structure, in both diseases. Our results also support the hypothesis that neurodegenerative syndromes such as AD and svPPA do not only implicate focal atrophies, but rather derive from a disconnection between various anatomical regions, and that clinical symptoms are caused by this rupture in the neural networks supporting cognitive functions such as semantic and episodic memory.