Background: Primary progressive aphasia (PPA) is a clinical dementia syndrome characterized by impairments in language. The presence of Alzheimer disease (AD) neuropathology has been observed in approximately 40% of PPA cases. Cross-sectional and longitudinal features of cortical atrophy in PPA are emerging but less is known about the integrity of subcortical structures, particularly the thalamus. As a major relay station in the brain, the thalamus is implicated in language functioning given its reciprocal connections with perisylvian regions in the cortex. High-dimensional brain mapping was used to characterize thalamic morphology in individuals with and without non-semantic PPA. Further, shape differences were compared between PPA participants with suspected AD pathology (PPAAβ +) and those without suspected AD pathology (PPAAβ -) as determined by amyloid PET scans. The relationship between shape and specific language deficits were also investigated. Method: Thalamic integrity was examined in 57 PPA participants relative to cognitively healthy controls (N=44) with similar demographics. MR scans were acquired using high-resolution T1-weighted MPRAGE volumes following the ADNI protocol. Thalamic shape features were estimated using Large Deformation Diffeomorphic Metric Mapping. Thalamic nuclei of interest included mediodorsal, pulvinar, and anterior regions. General linear models compared differences in thalamic shape between groups. Pearson models characterized relationships between thalamic nuclei and language function. Results: After controlling for whole brain volume, thalamic volume did not differ between groups [F(1, 99)=0.80, p=0.80]. However, PPA participants exhibited significant bilateral inward shape deformation in dorsal and ventral regions that extended in an anterior to posterior fashion, and unilateral outward deformation in medial and lateral regions only in the left thalamus relative to controls [F(9, 91)=5.75, p<0.001, Wilk's Λ=0.64]. There were no shape differences between PPAAβ + and PPAAβ – groups. Pearson models revealed significant correlations between confrontation naming and shape deformation in the left pulvinar (r=0.59, p<0.01) and left anterior (r=0.55, p<0.01) thalamic nuclei for the PPAAβ + group only, such that lower language scores reflected greater localized volume loss. Conclusions: In the absence of volumetric differences, shape measures were able to capture unique aspects of localized morphologic differences in PPA that corresponded to worse naming performance only in those with suspected AD pathology. Thalamic changes appear to be a contributing and unrecognized component to the presentation and language characterization of PPA.

Introdução: Indíviduos com danos cerebrais podem apresentar dissociação na produção de verbos e substantivos. Há uma maior diversidade de transtornos neurológicos que apresentam prejuízo na produção de verbos do que de substantivos, e esses transtornos normalmente apresentam danos em circuitos cerebrais frontais. No entanto, pouco se sabe sobre a natureza do prejuízo na produção de verbos em cada transtorno neurológico. Objetivo: A presente tese de doutorado teve como objetivo investigar a produção de verbos em diferentes doenças neurodegenerativas e no envelhecimento normal através das tarefas de fluência e nomeação de verbos. Métodos: para atingir o objetivo geral, foram realizados três estudos que originaram três artigos científicos. O primeiro artigo realizou uma adaptação da tarefa de fluência de verbos para o português brasileiro, obteve a performance de 62 brasileiros idosos saudáveis para esta tarefa e a influência de fatores demográficos, clínicos e da aplicação de outras tarefas de fluência verbal previamente à fluência de verbos. O segundo artigo investigou a natureza dos déficits da produção de verbos na doença de Alzheimer (DA). Para isso 35 pacientes com DA em fase leve e moderada foram avaliados para as tarefas de fluência e nomeação de verbos, assim como 35 idosos saudáveis (controles). Também analisou-se a influência da frequência das palavras nas tarefas estudadas. O terceiro artigo, investigou a natureza dos déficits na produção de verbos na Afasia Progressiva Primária (APP) não-fluente. Foram avaliados 12 pacientes com APP não-fluente e 9 sujeitos controle. Todos partcipantes foram avaliados através de tarefas de nomeação e fluência de verbos e de substantivos. Um efeito de manipulabilidade foi estudado na tarefa de nomeação. Correlatos neurais foram investigados utilizado a técnica de Voxel Based Morphometry (VBM) a partir de imagens de ressonância magnética (RM) estrutural dos pacientes. Resultados: No primeiro artigo obteve-se a performance dos idosos saudáveis na fluência de verbos (11,73±5,80), a correlação com a escolaridade (r=0,616), MEEM escore total (r=0,399), MEEM Atenção e Cálculo (r=0,393), e MEEM Linguagem (r=0,322). Não houve influência da aplicação prévia de tarefas de fluência verbal na fuência de verbos. No segundo artigo, os pacientes com DA mostraram prejuízo tanto na tarefa de nomeação de verbos (p<0,000; F=36,983) quanto na fluência de verbos (p<0,000; F=21,460), porém a primeira foi mais comprometida que a segunda. A performance dos pacientes com DA na nomeação de verbos foi influenciada pela severidade da doença e pela frequência das palavras. No terceiro artigo, os pacientes com APP não-fluente foram comprometidos em todas tarefas de nomeação e de fluência verbal, porém foram significativamente piores em verbos do que em substantivos. Não houve efeito de manipulabilidade. As áreas atróficas Broadmann 44 (p<0,001) e giro pré-central (p<0,001) se correlacionaram com o prejuízo na nomeação de verbos, enquanto as áreas atróficas 44 e 45 de Broadman (p<0,001, ambas) se correlacionaram com o prejuízo na fluência de verbos. Conclusões: Nossos achados indicam que o prejuízo na produção de verbos parece ter uma natureza predominantemente semântica na DA e prodominantemente gramatical na APP não fluente. As evidências levantam questões importantes também para a neurobiologia da linguagem. / Background: Individuals with brain damage may show dissociation in the verb and noun production. There is a larger diversity of neurological disorders that show impairment in verbs rather in nouns, and these disorders use to present damage in the frontal brain circuits. However, little is known about the nature of the verb production impairment in each one of these neurological disorders. Objective: The current doctoral thesis had the aim of investigating the verb production in different neurodegenerative diseases and in the normal elderly, using verb fluency and verb naming tasks. Methods: to reach the main aim, we carried out three studies that resulted in three articles. In the first article we adapted the verb fluency task for Brazilian Portuguese, we obtained the performance of 62 healthy elderly people for this task, and we verified the influence of demographic and clinical factors as well as of the previous application of other verbal fluency tasks. The second article investigated the nature of the verb production deficits in the Alzheimer’s disease (AD). Thirty-five mild and moderate AD patients and 35 healthy controls were evaluated for verb fluency and verb naming tasks. It also analyzed the influence of word frequency in the used tasks. The third article investigated the nature of verb production deficits in the nonfluent variant of Primary Progressive Aphasia (nfPPA). Twelve patients with nfPPA and 9 healthy controls were evaluated for verb and noun fluency and naming tasks. A manipulability effect was studied in the naming task. Neural correlates were investigated by Voxel Based Morphometry (VBM) of structural Magnetic Ressonance Imaging (MRI) of the patients. Results: The first article obtained the healthy elderly people performance for verb fluency (11.73±5.80), a correlation with education (r=0.616), MMSE total score (r=0.399), MMSE Attention and Calculation (r=0.393), and with MMSE Language (r=0.322). There was no influence of previous application of verbal fluency tasks on the verb fluency. In the second article, the AD patients showed deficits in the verb naming (p<0.000; F=36.983) and in the verb fluency (p<0.000; F=21.460), however the first task was more impaired than the second one. The AD patients performance in the verb naming was influenced by the disease severity and by word frequency. In the third article, the nfPPA patients were impaired in all naming and fluency tasks, however they were significantly worse in verbs than in nouns. There was no effect of manipulability. Atrophy on BA 44 (p<0.001) and on precentral gyrus (p<0.001) correlated with impairment in verb naming. Atrophy on BA 44 and 45 (p<0.001 for both) correlated with impairment in verb fluency. Conclusions: Our findings indicate the verb production deficits seem to have a more predominant semantic nature in AD and more predominant grammatical nature in nfPPA. This evidence brings up important questions for the neurobiology of language.

Introdução: Indíviduos com danos cerebrais podem apresentar dissociação na produção de verbos e substantivos. Há uma maior diversidade de transtornos neurológicos que apresentam prejuízo na produção de verbos do que de substantivos, e esses transtornos normalmente apresentam danos em circuitos cerebrais frontais. No entanto, pouco se sabe sobre a natureza do prejuízo na produção de verbos em cada transtorno neurológico. Objetivo: A presente tese de doutorado teve como objetivo investigar a produção de verbos em diferentes doenças neurodegenerativas e no envelhecimento normal através das tarefas de fluência e nomeação de verbos. Métodos: para atingir o objetivo geral, foram realizados três estudos que originaram três artigos científicos. O primeiro artigo realizou uma adaptação da tarefa de fluência de verbos para o português brasileiro, obteve a performance de 62 brasileiros idosos saudáveis para esta tarefa e a influência de fatores demográficos, clínicos e da aplicação de outras tarefas de fluência verbal previamente à fluência de verbos. O segundo artigo investigou a natureza dos déficits da produção de verbos na doença de Alzheimer (DA). Para isso 35 pacientes com DA em fase leve e moderada foram avaliados para as tarefas de fluência e nomeação de verbos, assim como 35 idosos saudáveis (controles). Também analisou-se a influência da frequência das palavras nas tarefas estudadas. O terceiro artigo, investigou a natureza dos déficits na produção de verbos na Afasia Progressiva Primária (APP) não-fluente. Foram avaliados 12 pacientes com APP não-fluente e 9 sujeitos controle. Todos partcipantes foram avaliados através de tarefas de nomeação e fluência de verbos e de substantivos. Um efeito de manipulabilidade foi estudado na tarefa de nomeação. Correlatos neurais foram investigados utilizado a técnica de Voxel Based Morphometry (VBM) a partir de imagens de ressonância magnética (RM) estrutural dos pacientes. Resultados: No primeiro artigo obteve-se a performance dos idosos saudáveis na fluência de verbos (11,73±5,80), a correlação com a escolaridade (r=0,616), MEEM escore total (r=0,399), MEEM Atenção e Cálculo (r=0,393), e MEEM Linguagem (r=0,322). Não houve influência da aplicação prévia de tarefas de fluência verbal na fuência de verbos. No segundo artigo, os pacientes com DA mostraram prejuízo tanto na tarefa de nomeação de verbos (p<0,000; F=36,983) quanto na fluência de verbos (p<0,000; F=21,460), porém a primeira foi mais comprometida que a segunda. A performance dos pacientes com DA na nomeação de verbos foi influenciada pela severidade da doença e pela frequência das palavras. No terceiro artigo, os pacientes com APP não-fluente foram comprometidos em todas tarefas de nomeação e de fluência verbal, porém foram significativamente piores em verbos do que em substantivos. Não houve efeito de manipulabilidade. As áreas atróficas Broadmann 44 (p<0,001) e giro pré-central (p<0,001) se correlacionaram com o prejuízo na nomeação de verbos, enquanto as áreas atróficas 44 e 45 de Broadman (p<0,001, ambas) se correlacionaram com o prejuízo na fluência de verbos. Conclusões: Nossos achados indicam que o prejuízo na produção de verbos parece ter uma natureza predominantemente semântica na DA e prodominantemente gramatical na APP não fluente. As evidências levantam questões importantes também para a neurobiologia da linguagem. / Background: Individuals with brain damage may show dissociation in the verb and noun production. There is a larger diversity of neurological disorders that show impairment in verbs rather in nouns, and these disorders use to present damage in the frontal brain circuits. However, little is known about the nature of the verb production impairment in each one of these neurological disorders. Objective: The current doctoral thesis had the aim of investigating the verb production in different neurodegenerative diseases and in the normal elderly, using verb fluency and verb naming tasks. Methods: to reach the main aim, we carried out three studies that resulted in three articles. In the first article we adapted the verb fluency task for Brazilian Portuguese, we obtained the performance of 62 healthy elderly people for this task, and we verified the influence of demographic and clinical factors as well as of the previous application of other verbal fluency tasks. The second article investigated the nature of the verb production deficits in the Alzheimer’s disease (AD). Thirty-five mild and moderate AD patients and 35 healthy controls were evaluated for verb fluency and verb naming tasks. It also analyzed the influence of word frequency in the used tasks. The third article investigated the nature of verb production deficits in the nonfluent variant of Primary Progressive Aphasia (nfPPA). Twelve patients with nfPPA and 9 healthy controls were evaluated for verb and noun fluency and naming tasks. A manipulability effect was studied in the naming task. Neural correlates were investigated by Voxel Based Morphometry (VBM) of structural Magnetic Ressonance Imaging (MRI) of the patients. Results: The first article obtained the healthy elderly people performance for verb fluency (11.73±5.80), a correlation with education (r=0.616), MMSE total score (r=0.399), MMSE Attention and Calculation (r=0.393), and with MMSE Language (r=0.322). There was no influence of previous application of verbal fluency tasks on the verb fluency. In the second article, the AD patients showed deficits in the verb naming (p<0.000; F=36.983) and in the verb fluency (p<0.000; F=21.460), however the first task was more impaired than the second one. The AD patients performance in the verb naming was influenced by the disease severity and by word frequency. In the third article, the nfPPA patients were impaired in all naming and fluency tasks, however they were significantly worse in verbs than in nouns. There was no effect of manipulability. Atrophy on BA 44 (p<0.001) and on precentral gyrus (p<0.001) correlated with impairment in verb naming. Atrophy on BA 44 and 45 (p<0.001 for both) correlated with impairment in verb fluency. Conclusions: Our findings indicate the verb production deficits seem to have a more predominant semantic nature in AD and more predominant grammatical nature in nfPPA. This evidence brings up important questions for the neurobiology of language.

Introdução: Indíviduos com danos cerebrais podem apresentar dissociação na produção de verbos e substantivos. Há uma maior diversidade de transtornos neurológicos que apresentam prejuízo na produção de verbos do que de substantivos, e esses transtornos normalmente apresentam danos em circuitos cerebrais frontais. No entanto, pouco se sabe sobre a natureza do prejuízo na produção de verbos em cada transtorno neurológico. Objetivo: A presente tese de doutorado teve como objetivo investigar a produção de verbos em diferentes doenças neurodegenerativas e no envelhecimento normal através das tarefas de fluência e nomeação de verbos. Métodos: para atingir o objetivo geral, foram realizados três estudos que originaram três artigos científicos. O primeiro artigo realizou uma adaptação da tarefa de fluência de verbos para o português brasileiro, obteve a performance de 62 brasileiros idosos saudáveis para esta tarefa e a influência de fatores demográficos, clínicos e da aplicação de outras tarefas de fluência verbal previamente à fluência de verbos. O segundo artigo investigou a natureza dos déficits da produção de verbos na doença de Alzheimer (DA). Para isso 35 pacientes com DA em fase leve e moderada foram avaliados para as tarefas de fluência e nomeação de verbos, assim como 35 idosos saudáveis (controles). Também analisou-se a influência da frequência das palavras nas tarefas estudadas. O terceiro artigo, investigou a natureza dos déficits na produção de verbos na Afasia Progressiva Primária (APP) não-fluente. Foram avaliados 12 pacientes com APP não-fluente e 9 sujeitos controle. Todos partcipantes foram avaliados através de tarefas de nomeação e fluência de verbos e de substantivos. Um efeito de manipulabilidade foi estudado na tarefa de nomeação. Correlatos neurais foram investigados utilizado a técnica de Voxel Based Morphometry (VBM) a partir de imagens de ressonância magnética (RM) estrutural dos pacientes. Resultados: No primeiro artigo obteve-se a performance dos idosos saudáveis na fluência de verbos (11,73±5,80), a correlação com a escolaridade (r=0,616), MEEM escore total (r=0,399), MEEM Atenção e Cálculo (r=0,393), e MEEM Linguagem (r=0,322). Não houve influência da aplicação prévia de tarefas de fluência verbal na fuência de verbos. No segundo artigo, os pacientes com DA mostraram prejuízo tanto na tarefa de nomeação de verbos (p<0,000; F=36,983) quanto na fluência de verbos (p<0,000; F=21,460), porém a primeira foi mais comprometida que a segunda. A performance dos pacientes com DA na nomeação de verbos foi influenciada pela severidade da doença e pela frequência das palavras. No terceiro artigo, os pacientes com APP não-fluente foram comprometidos em todas tarefas de nomeação e de fluência verbal, porém foram significativamente piores em verbos do que em substantivos. Não houve efeito de manipulabilidade. As áreas atróficas Broadmann 44 (p<0,001) e giro pré-central (p<0,001) se correlacionaram com o prejuízo na nomeação de verbos, enquanto as áreas atróficas 44 e 45 de Broadman (p<0,001, ambas) se correlacionaram com o prejuízo na fluência de verbos. Conclusões: Nossos achados indicam que o prejuízo na produção de verbos parece ter uma natureza predominantemente semântica na DA e prodominantemente gramatical na APP não fluente. As evidências levantam questões importantes também para a neurobiologia da linguagem. / Background: Individuals with brain damage may show dissociation in the verb and noun production. There is a larger diversity of neurological disorders that show impairment in verbs rather in nouns, and these disorders use to present damage in the frontal brain circuits. However, little is known about the nature of the verb production impairment in each one of these neurological disorders. Objective: The current doctoral thesis had the aim of investigating the verb production in different neurodegenerative diseases and in the normal elderly, using verb fluency and verb naming tasks. Methods: to reach the main aim, we carried out three studies that resulted in three articles. In the first article we adapted the verb fluency task for Brazilian Portuguese, we obtained the performance of 62 healthy elderly people for this task, and we verified the influence of demographic and clinical factors as well as of the previous application of other verbal fluency tasks. The second article investigated the nature of the verb production deficits in the Alzheimer’s disease (AD). Thirty-five mild and moderate AD patients and 35 healthy controls were evaluated for verb fluency and verb naming tasks. It also analyzed the influence of word frequency in the used tasks. The third article investigated the nature of verb production deficits in the nonfluent variant of Primary Progressive Aphasia (nfPPA). Twelve patients with nfPPA and 9 healthy controls were evaluated for verb and noun fluency and naming tasks. A manipulability effect was studied in the naming task. Neural correlates were investigated by Voxel Based Morphometry (VBM) of structural Magnetic Ressonance Imaging (MRI) of the patients. Results: The first article obtained the healthy elderly people performance for verb fluency (11.73±5.80), a correlation with education (r=0.616), MMSE total score (r=0.399), MMSE Attention and Calculation (r=0.393), and with MMSE Language (r=0.322). There was no influence of previous application of verbal fluency tasks on the verb fluency. In the second article, the AD patients showed deficits in the verb naming (p<0.000; F=36.983) and in the verb fluency (p<0.000; F=21.460), however the first task was more impaired than the second one. The AD patients performance in the verb naming was influenced by the disease severity and by word frequency. In the third article, the nfPPA patients were impaired in all naming and fluency tasks, however they were significantly worse in verbs than in nouns. There was no effect of manipulability. Atrophy on BA 44 (p<0.001) and on precentral gyrus (p<0.001) correlated with impairment in verb naming. Atrophy on BA 44 and 45 (p<0.001 for both) correlated with impairment in verb fluency. Conclusions: Our findings indicate the verb production deficits seem to have a more predominant semantic nature in AD and more predominant grammatical nature in nfPPA. This evidence brings up important questions for the neurobiology of language.

Non-cognitive features including personality changes are increasingly recognized in the three PPA variants (semantic-svPPA, non fluent-nfvPPA, and logopenic-lvPPA). However, differences in emotion processing among the PPA variants and its association with white matter tracts are unknown. We compared emotion detection across the three PPA variants and healthy controls (HC), and related them to white matter tract integrity and cortical degeneration. Personality traits in the PPA group were also examined in relation to white matter tracts. Thirty-three patients with svPPA, nfvPPA, lvPPA, and 32 HC underwent neuropsychological assessment, emotion evaluation task (EET), and MRI scan. Patients' study partners were interviewed on the Clinical Dementia Rating Scale (CDR) and completed an interpersonal traits assessment, the Interpersonal Adjective Scale (IAS). Diffusion tensor imaging of uncinate fasciculus (UF), superior longitudinal fasciculus (SLF) and inferior longitudinal fasciculus (ILF), and voxel-based morphometry to derive gray matter volumes for orbitofrontal cortex (OFC), anterior temporal lobe (ATL) regions were performed. In addition, gray matter volumes of white matter tract-associated regions were also calculated: inferior frontal gyrus (IFG), posterior temporal lobe (PTL), inferior parietal lobe (IPL) and occipital lobe (OL). ANCOVA was used to compare EET performance. Partial correlation and multivariate linear regression were conducted to examine association between EET and neuroanatomical regions affected in PPA. All three variants of PPA performed significantly worse than HC on EET, and the svPPA group was least accurate at recognizing emotions. Performance on EET was related to the right UF, SLF, and ILF integrity. Regression analysis revealed EET performance primarily relates to the right UF integrity. The IAS subdomain, cold-hearted, was also associated with right UF integrity. Disease-specific emotion recognition and personality changes occur in the three PPA variants and are likely associated with disease-specific neuroanatomical changes. Loss of white matter integrity contributes as significantly as focal atrophy in behavioral changes in PPA.

Background: The presence of AD pathology can result in diverse behavioral phenotypes, including the typical amnestic variant characterized by memory deficits, and an atypical aphasic variant characterized by language deficits. Previous research has identified unique cortical atrophy patterns in each phenotype, though less focus has been drawn to subcortical involvement. The current study sought to dissociate these behavioral phenotypes by characterizing their thalamic volume and shape features using high-dimensional brain mapping procedures. Relationships between brain metrics and specific language and memory deficits were also investigated in aphasic AD and amnestic AD, respectively. Method: Thalamic integrity was examined in aphasic AD (n = 25), amnestic AD (n = 21), and healthy control participants (n = 44). Age and supratentorial volume (STV) were used as covariates in all analyses. MR scans were acquired using high-resolution T1-weighted MPRAGE volumes following the ADNI protocol. Thalamic shape features were estimated using Large Deformation Diffeomorphic Metric Mapping. General linear models compared differences in thalamic shape between groups. Pearson correlation coefficients characterized relationships between thalamic nuclei (pulvinar, anterior, and mediodorsal) and language and memory performance in aphasic AD and amnestic AD, respectively. Results: After controlling for age and STV, thalamic volume did not differ between groups [F (2,85) = 2.55, p = 08]. However, AD phenotypes exhibited bilateral inward shape deformation in dorsal and ventral regions extending in an anterior to posterior fashion [left: F(20, 154) = 2.61, p < .001; right: F(20,154)= 2.26, p < .01]. Amnestic AD demonstrated right ventrolateral localized volume loss relative to aphasic AD. Pearson models revealed lower confrontation naming was correlated with localized volume loss of bilateral pulvinar (left: r = .59, p < .01; right: r = .55, p < .01), and bilateral anterior (left: r = .50, p = .01; right: r = .49, p = .01) thalamic nuclei for aphasic AD; lower delayed recall was significantly correlated with localized volume loss in left anterior (r = .46, p = .04) thalamic nuclei in amnestic AD. Conclusions: In the absence of volumetric differences, shape measures captured distinct patterns of localized volume loss in aphasic AD and amnestic AD behavioral phenotypes relative to control participants. Comparisons of AD variants demonstrated inward deformation in amnestic AD, particularly in right ventrolateral regions. Thalamic changes appear to be implicated in AD pathology, with relationships to the expected cognitive impairments, although thalamic atrophy patterns are unable to fully dissociate behavioral phenotypes.

Η παρούσα εργασία εστιάζει στον τρόπο επεξεργασίας των σύνθετων λέξεων της Νέας Ελληνικής (ΝΕ) στην Πρωτοπαθή Προοδευτική Αφασία με αγραμματικό λόγο (ΠΠΑ-α). Οι μέχρι τώρα έρευνες επικεντρώνονται κυρίως σε κλινικές περι- πτώσεις αφασίας από κάποια εστιακή εγκεφαλική βλάβη (ΕΑ), ενώ η ΠΠΑ δεν έχει μελετηθεί ως προς το ζήτημα αυτό τόσο στη ΝΕ όσο και διαγλωσσικά. Στόχο, λοι- πόν, της συγκεκριμένης εργασίας αποτελεί η εξέταση του κατά πόσο ελληνόφωνοι ασθενείς με ΠΠΑ-α παρουσιάζουν ελλείμματα στην κατονομασία σύνθετων λέξεων. Μέθοδος: Διεξαγωγή πειράματος κατονομασίας μέσω ορισμού (naming on definition task), το οποίο αφορά την κατονομασία σύνθετων λέξεων της ΝΕ. Συμμετέχοντες: 2 ΠΠΑ-α ασθενείς (ο πρώτος σε πιο πρώιμο στάδιο της ΠΠΑ-α σε σχέση με το δεύτερο) και 2 άτομα που συνιστούν την ομάδα ελέγχου (controls). Πειραματικό υλικό: 71 σύνθετα της ΝΕ, 45 υποτακτικά (π.χ. μολυβοθήκη, μαυροπί- νακας, σιγοτραγουδώ), 15 παρατακτικά (π.χ. αλατοπίπερο, βορειοδυτικός) και 11 εξωκεντρικά (π.χ. κοκκινομάλλης, κακόγουστος).Υποθέσεις: Σύμφωνα με τα πορίσματα της τρέχουσας βιβλιογραφίας, ασθενείς με αγραμματικού τύπου ΕΑ και ΠΠΑ-α εμφανίζουν παρόμοια επίδοση σε πειράματα που ελέγχουν τη μορφοσύνταξη (Thompson et al.). Έτσι, αναμένεται να έχουν εξί- σου παρόμοια επίδοση και όσον αφορά την επεξεργασία συνθέτων, αφού η σύνθεση αποτελεί μία αμιγώς μορφολογική διαδικασία. Βάσει του παραπάνω παραλληλι- σμού, υποθέτουμε πως οι ΠΠΑ-α ασθενείς θα κατονομάζουν ευκολότερα τα σημα- σιολογικά διαφανή σύνθετα (πρώτη υπόθεση), θα διατηρούν τη γνώση της δομής του συνθέτου (δεύτερη υπόθεση), θα διατηρούν τα όρια των επιμέρους συστατικών σε πιθανά λάθη υποκατάστασης ή παράλειψης (τρίτη υπόθεση), και θα προβαίνουν σε ανάκληση του συνθέτου μέσω τεμαχισμού στα επιμέρους συστατικά του (τέταρτηυπόθεση). Τέλος, αν το συστατικό-κεφαλή έχει κάποιο βασικό ρόλο στη διαδικασία της κατονομασίας, αναμένονται συστηματικά περισσότερα λάθη σε αυτό το συστα- τικό (πέμπτη υπόθεση). Ακόμη, στο επίκεντρο του ενδιαφέροντος βρίσκονται και κάποια επιπλέον ερωτήματα που αφορούν το αν και κατά πόσο υπάρχει όντως σύ- γκλιση μεταξύ της ΠΠΑ-α και της ΕΑ-α στην κατονομασία σύνθετων λέξεων, το αν υπάρχει συσχέτιση μεταξύ του είδους/αριθμού των λαθών και του τύπου συνθέτου και το αν υφίστανται πρόβλημα με συστατικά συγκεκριμένης γραμματικής κατηγο- ρίας. Αποτελέσματα: Τα αποτελέσματα του πειράματος ανέδειξαν σημαντικές διαφορές στην επίδοση των δύο ασθενών. Ειδικότερα, ο πρώτος ασθενης είχε περισσότερα λάθη υποκατάστασης, τα οποία σηματοδοτούν επίγνωση της σύνθετης δομής και ανάκληση του συνθέτου μέσω τεμαχισμού στα επιμέρους συστατικά του. Αντίθετα, η δεύτερη ασθενής είχε περισσότερα λάθη περίφρασης και απάντησης με μία λέξη- λέξημα, ενώ ο στόχος ήταν η απάντηση με σύνθετη λέξη. Έτσι, τα λάθη της δεύ- τερης ασθενούς παραπέμπουν σε μη επίγνωση της σύνθετης δομής και σε μία πιο ολιστική διαδικασία ανάκλησης του συνθέτου. Τέλος, τα περισσότερα λάθη και των δύο ασθενών έγιναν σε υποτακτικά σύνθετα της γραμματικής κατηγορίας του ονό- ματος, ενώ δεν εντοπίστηκε επίδραση τόσο της σημασιολογικής διαφάνειας όσο και της μορφολογικής κεφαλής. Συμπεράσματα: Από την ανάλυση των αποτελεσμάτων γίνεται σαφές πως το στά- διο της διαταραχής καθορίζει και το είδος των γλωσσικών ελλειμμάτων. Συγκεκρι- μένα, στα πρώιμα στάδια της ΠΠΑ-α εμφανίζονται γλωσσικά ελλείμματα τα οποία συγκλίνουν με αυτά της ΕΑ-α, ενώ σε μετέπειτα στάδια η ικανότητα κατονομασίας πλήττεται σοβαρά διαμορφώνοντας ένα ιδιαίτερο κλινικό προφίλ, το οποίο δεν φαί- νεται να συγκλίνει ξεκάθαρα με κάποιον άλλο παθολογικό πληθυσμό. Αναλυτικό- τερα, στα αρχικά στάδια το πρόβλημα εδράζεται στην ενεργοποίηση της φωνολο- γικής μορφής της λέξης, ενώ οι μορφολογικοί κανόνες φαίνεται ότι διατηρούνται (γνώση της σύνθετης δομής, ορίων των συστατικών). Αντίθετα, σε μετέπειτα στά- δια το πρόβλημα εντοπίζεται στην ενεργοποίηση τόσο της φωνολογικής όσο και της μορφολογικής δομής του συνθέτου. Σε ό,τι αφορά τα υποτακτικά σύνθετα, η αυξη- μένη δυσκολία που δημιουργούν μπορεί να συσχετιστεί με τη λειτουργική σχέση των επιμέρους συστατικών τους. Εν κατακλείδι, η παρούσα εργασία αποτελεί μία πρώτη προσπάθεια μελέτης της σύνθεσης στην ΠΠΑ-α. Η ανάλυση των αποτελεσμάτων έφερε στο φως μία σειρά από γλωσσικά ελλείμματα, τα οποία αναμένεται να ελεγχθούν σε μεγαλύτερο δείγμα ΠΠΑ-α ασθενών για τον καθορισμό ασφαλέστερων συμπερασμάτων. / The present study is focused on the agrammatic variant of Primary Progressive Aphasia (PPA-a), which is a language impairment caused by neurodegenerative disease and characterized by difficulties in processing the grammatical aspects of speech (Mesulam, 2013). PPA-a has not examined about the grammatical deficits in Modern Greek (MG). Therefore, the aim of the present study is to examine if the Greek-speaking individuals with PPA-a have problems in naming compound words in MG. Procedure: Naming definition task of compound words in MG. Participants: Two patients with PPA-a (the first patient is in earlier stage of the disease than the other patient). Stimulus set: 71 compounds in MG, 45 subordinate compounds (e.g. [molivo’θici]>pencil case, [mavro’pinakas]>blackboard), 15 coordinate compounds (e.g. [alato’pipero]>salt and pepper, [vorioδiti’kos]>northwest) and 11 exocentric compounds (e.g. [kokkino’malis]>redhead, [ka’koγustos]>vulgar/tasteless). Hypotheses: According to the recent bibliography, agrammatic patients caused by stroke (StrAgr) and PPA-a patients have common performance in tasks which examine the morphosyntax (Thompson et al. 2013). So, PPA-a is expected to have the same deficits with StrAgr in naming compounds, given that compounding is a pure morphological procedure. Specifically, we expected compound effect, semantic transparency effect and lexical access through decomposition. Results: The error analysis showed differences in the performance of the two patients respect to the stage of the disease. Specifically, in the early stage substitution errors were occurred, supporting compound effect and a view of lexical access through decomposition. On the contrary, noncomposed semantic paraphasias and single words errors were occurred mainly at a later stage , indicating a more holistic access. Finally, the most errors were in subordinate compounds, whereas no effect of headedness and semantic transparency were found. Discussion: The results produce clear evidence that the stage of the PPA-a can affect the kind of the linguistic deficits. Specifically, in the initial stages, the linguistic deficits resemble with those of StrAgr patients with problems in the activation of the phonological form of the compound, whereas the morphological rules are intact. On the other hand, the naming competence is more impaired and distinctly different from other pathological populations at a later stage. Specifically, there are problems in the activation of both the phonological and the morphological compound forms. Finally, the increased difficulty with subordinate compounds will be correlated with the grammatical relations holding between the constituents.

Orientador: Rosana do Carmo Novaes Pinto / Dissertação (mestrado) - Universidade Estadual de Campinas, Instituto de Estudos da Linguagem / Made available in DSpace on 2018-08-13T12:43:32Z (GMT). No. of bitstreams: 1 Canoas-Andrade_Rosangela_M.pdf: 2122155 bytes, checksum: e41f3e8059727d732ec7dd6d0bd9d6f8 (MD5) Previous issue date: 2009 / Resumo: A Fonoaudiologia tradicional, com relação às alterações da linguagem, ainda sofre a forte influência teórica e metodológica dos discursos que circulam na área médica. As abordagens orgânicas são geralmente priorizadas, em detrimento de análises mais abrangentes dos fenômenos e, principalmente, dos sujeitos. Essa visão redutora, inevitavelmente, também é que vai dar as diretrizes para o acompanhamento terapêutico. Orientado pela abordagem teórica e metodológica da Neurolingüística Discursiva (ND), este trabalho apresenta um estudo longitudinal de um caso de Afasia Fluente Progressiva, para o qual contribuem o histórico neurológico - constituído por imagens tomográficas e laudos que revelam lesões em várias áreas cerebrais, em decorrência de AVCs focais e isquêmicos, clipagem de aneurismas e atrofias corticais e sub-corticais, além dos resultados de avaliações neuropsicológicas e as análises lingüísticas de episódios dialógicos. Os dados analisados foram obtidos em episódios dialógicos ocorridos nas sessões semanais do Grupo III do CCA (Centro de Convivência de Afásicos) e em sessões individuais de acompanhamento fonoaudiológico, durante as quais também foram desenvolvidas algumas atividades metalingüísticas, com o objetivo de respaldar nossas hipóteses sobre suas dificuldades lingüísticas e cognitivas. Trata-se de um caso que consideramos singular, pois revela os efeitos das práticas sociais e do exercício real com a linguagem, tanto no curso do desenvolvimento de sua afasia, como das alterações cognitivas. A instabilidade presente no caso de AJ, cujos enunciados às vezes em nada diferem da normalidade, outras vezes revelam dificuldades próprias de sua afasia e, em determinados momentos assemelham-se aos quadros iniciais de demência, contribui para a reflexão acerca da relação normal/patológico.Por fim, discute-se o impacto da abordagem da ND para a clínica fonoaudiológica, na avaliação da linguagem e, principalmente, no acompanhamento terapêutico de sujeitos afásicos ou com outras alterações lingüísticas e cognitivas / Abstract: The traditional Speech Therapy, when the focus is language alterations, is still strongly influenced by the theoretical and methodological discourses from the medical field. Organic approaches are usually privileged in comparison to other approaches, other possibilities of analysis of the phenomena and, especially, of the subjects. This reductionist view, inevitably, is the one that will provide the guidelines for language therapy. Guided by the theoretical and methodological approach of Discursive Neurolinguistics (ND), this research presents a longitudinal study of a case of Fluent Progressive Aphasia. We present the neurological history of the case - which consists of tomography images and reports, which reveal lesions in various brain areas, due to strokes - focal and ischemic, clipping of aneurysms and cortical & sub-cortical atrophies. We also present the results of neuropsychological assessments and the analysis of linguistic episodes. Data were obtained during episodes occurred in the weekly discussion of Group III of CCA (Centro de Convivência de Afásicos) and in individual sessions of speech therapy, during which some metalinguistic activities were developed, with the aim of supporting our hypothesis about his linguistic and cognitive difficulties. This is a case that we consider unique, because it shows the effects of social and linguistic practices on the development of aphasia and on the cognitive changes. The instability that characterizes the case contributes to the debate / Mestrado / Linguistica / Mestre em Linguística

For two decades, researchers and clinicians have been using the diagnostic criteria for FTD to generally diagnose a patient as suffering from PPA and the criteria of Neary et al. (1998) to further specify the diagnosis as progressive nonfluent aphasia or semantic dementia. However, there were a number of PPA cases that could not be classified according to the criteria of Neary and colleagues, which led to a revision of the diagnostic clinical and research criteria for PPA by Gorno-Tempini et al. (2011). The revised criteria encompass three PPA variants (svPPA, nfvPPA, and lvPPA) with three stages characterized by increasing evidence: clinical diagnosis, imaging-supported diagnosis, and diagnosis with definite pathology. As compared to the previous diagnostic criteria, more emphasis is placed on imaging markers as supportive features. These imaging criteria were however proposed based on a purely qualitative evaluation of the literature and have not been validated so far. The aim of this thesis was to quantitatively evaluate the validity of the new diagnostic imaging criteria for PPA variants using anatomical likelihood meta-analyses (study 1) and to investigate the usefulness of these imaging criteria for the individual diagnosis of PPA patients in clinical routine using support vector machine classification (study 2).

Introdução: No Brasil há carência de instrumentos validados para a análise do curso da Demência Frontotemporal (DFT). Dessa forma, torna-se relevante a validação da Escala de Estadiamento e Progressão da Demência Frontotemporal (FTD-FRS). Em nosso meio, as escalas de estadiamento das demências, como a Clinical Dementia Rating (CDR), foram elaboradas para graduar a doença de Alzheimer (DA) e não incluem os sintomas específicos da DFT. Objetivos: 1. Realizar a tradução, adaptação transcultural e validação da FTD-FRS para o contexto brasileiro. 2. Avaliar a capacidade da FTD-FRS detectar alterações em pacientes com DFTvc, afasia progressiva primária (APP) e DA após 12 meses da avaliação inicial, em comparação com a escala CDR para DLFT, e com a CDR original. Métodos: Participaram do estudo 101 indivíduos com idade igual ou superior a 40 anos, com escolaridade formal acima de dois anos, sendo 31 pacientes com diagnóstico de DFT variante comportamental (DFTvc), doze pacientes com afasia progressiva primária (APP), 28 pacientes com doença de Alzheimer (DA), oito com comprometimento cognitivo leve (CCL) e 22 controles normais (CN). Foram entrevistados os familiares ou cuidadores que tinham contato frequente com o paciente. Os pacientes com DA, e com os subtipos de DFT foram pareados quanto à gravidade da doença, segundo a CDR. Resultados: Foi realizado o processo de adaptação transcultural da FTD-FRS. Consistiu em: tradução, retrotradução (realizadas por tradutores independentes), discussão com especialistas sobre a versão em português e equivalência com a versão original, e desenvolvimento da versão final. A consistência interna da FTD-FRS, estimada pelo alfa de Cronbach foi 0,975, e o coeficiente de correlação intra-classe, para a estabilidade no teste e reteste em seis meses foi de 0,977. A análise fatorial revelou a existência de quatro fatores que se correlacionaram significativamente com os domínios da CDR-DLFT. Os pacientes com DFTvc apresentaram progressão mais rápida em 12 meses do que os demais subtipos de demência na FTD-FRS, na CDR-DLFT e na CDR-original. Considerações finais: A FTD-FRS tem propriedades psicométricas adequadas para seu uso clínico no Brasil. Este instrumento pode auxiliar na caracterização de sintomas clínicos relevantes para o diagnóstico e estadiamento da DFT. Também pode documentar os resultados relacionados à intervenção terapêutica. Este estudo fornece aos clínicos e pesquisadores um instrumento válido para estadiamento e acompanhamentode de pacientes diagnosticados com DFT / Introduction: In Brazil there is a shortage of validated instruments for the analysis of the course of Frontotemporal Dementia (FTD). Thus, the validation of the Frontotemporal Dementia Staging and Progression Scale (FTD-FRS) becomes relevant. In our setting, dementia staging scales, such as the Clinical Dementia Rating (CDR), were designed to stage Alzheimer\'s disease (AD) and did not include the specific symptoms of FTD. Objectives: 1. To perform the translation, cross-cultural adaptation and validation of the FTD-FRS for the Brazilian context. 2. Evaluate the ability of the FTD-FRS to detect changes in patients with bvFTD, primary progressive aphasia (PPA) and AD after 12 months of the initial evaluation, compared to the CDR scale for FTLD, and with the original CDR. Methods: A total of 101 individuals aged 40 years and older, with formal schooling above two years of age, were included in the study. Twenty-one patients were diagnosed with bvFTD, twelve patients with PPA, 28 AD, eight with mild cognitive impairment (MCI) and 22 normal controls (NC). Family members or caregivers who had frequent contact with the patient were interviewed. Patients with AD and with FTD subtypes were matched for disease severity, according to CDR. Results: The process of cross-cultural adaptation of the FTD-FRS was carried out. It consisted of: translation, back-translation (carried out by independent translators), discussion with experts about the Portuguese version and equivalence with the original version, and development of the final version. The internal consistency of the FTD-FRS, estimated by the Cronbach\'s alpha was 0.975, and the intra-class correlation coefficient for the test and retest stability at six months was 0.977. Factor analysis revealed the existence of four factors that correlated significantly with the CDR-DLFT domains. Patients with bvFTD showed faster progression at 12 months than the other dementia subtypes in the FTD-FRS, CDR-DLFT and CDR-original version scales. Final considerations: FTD-FRS has psychometric properties suitable for clinical use in Brazil. This instrument may aid in the characterization of clinical symptoms relevant to the diagnosis and staging of FTD. It can also document the results related to therapeutic interventions. This study provides clinicians and researchers with a valid instrument for staging and follow-up of patients diagnosed with FTD