abstract: Neurodegenerative diseases such as Alzheimer’s disease, Parkinson’s disease, or amyotrophic lateral sclerosis are defined by the loss of several types of neurons and glial cells within the central nervous system (CNS). Combatting these diseases requires a robust population of relevant cell types that can be employed in cell therapies, drug screening, or patient specific disease modeling. Human induced pluripotent stem cells (hiPSC)-derived neural progenitor cells (hNPCs) have the ability to self-renew indefinitely and differentiate into the various neuronal and glial cell types of the CNS. In order to realize the potential of hNPCs, it is necessary to develop a xeno-free scalable platform for effective expansion and differentiation. Previous work in the Brafman lab led to the engineering of a chemically defined substrate—vitronectin derived peptide (VDP), which allows for the long-term expansion and differentiation of hNPCs. In this work, we use this substrate as the basis for a microcarrier (MC)-based suspension culture system. Several independently derived hNPC lines were cultured on MCs for multiple passages as well as efficiently differentiated to neurons. Finally, this MC-based system was used in conjunction with a low shear rotating wall vessel (RWV) bioreactor for the integrated, large-scale expansion and neuronal differentiation of hNPCs. Finally, VDP was shown to support the differentiation of hNPCs into functional astrocytes. Overall, this fully defined and scalable biomanufacturing system will facilitate the generation of hNPCs and their derivatives in quantities necessary for basic and translational applications. / Dissertation/Thesis / Masters Thesis Biomedical Engineering 2018

Submitted by Rosana Amâncio (rosana.amancio@ufcg.edu.br) on 2018-07-24T13:48:59Z No. of bitstreams: 1 SAMUEL ANDRADE DO NASCIMENTO - DISSERTAÇÃO PPGCNBio 2015..pdf: 5482564 bytes, checksum: 07458737252bdc2848bf45e49123f07d (MD5) / Made available in DSpace on 2018-07-24T13:48:59Z (GMT). No. of bitstreams: 1 SAMUEL ANDRADE DO NASCIMENTO - DISSERTAÇÃO PPGCNBio 2015..pdf: 5482564 bytes, checksum: 07458737252bdc2848bf45e49123f07d (MD5) Previous issue date: 2015-07-09 / Neste trabalho, apresentamos um estudo das propriedades optoeletrônicas, vibracionais e termodinâmicas de inibidores de acetilcolinesterase, realizadas por meio de cálculos quânticos através da teoria do funcional da densidade, utilizando a aproximação da densidade local (Local Density Approximation - LDA) e a aproximação do gradiente generalizado (Generalized Gradient Approximation - GGA). As moléculas em estudo possuem a capacidade de inibir a ação da enzima acetilcolinesterase, que age diretamente nas transmissões sinápticas no sistema nervoso central; atribui-se a estes inibidores a capacidade de colaborar para melhores níveis de acetilcolina no organismo humano; acetilcolina por sua vez é um neurotransmissor, e sua presença no organismo é essencial a manutenção e desenvolvimento cognitivo humano; acredita-se ainda que a ausência deste neurotransmissor conduz ao estado de demência, causando uma doença conhecida por Mal de Alzheimer. Os medicamentos selecionados para este estudo foram a Tacrina, o Donepezil, a Rivastigmina, a Galantamina e a Fisostigmina. Para a realização dos cálculos foi utilizado o software de simulação computacional Conformers aplicado para os cálculos conformacionais e para as demais propriedades o DMol³. As propriedades foram obtidas para a estrutura molecular de menor energia de cada molécula, sendo possível realizar estudo sobre os orbitais moleculares HOMO e LUMO, densidade de estado (PDOS), além dos espectros de absorção óptica, Infravermelho (Infrared - IR) e espalhamento Raman. As propriedades termodinâmicas calculadas foram a entropia, entalpia, energia livre e a capacidade térmica. Todos os cálculos foram realizados utilizando os funcionais LDA/PWC e GGA/PBE. / In this work we present a study for a optoeletronic, vibrational and thermodynamic properties of Acetylcholinesterase Inhibitors, conducted through quantum calculations by Density Functional Theory, using the Local Density Approximation - LDA and Generalized Gradient Approximation - GGA. These molecules have the capacity to inhibit the action of the enzyme acetylcholinesterase, which acts directly on synaptic transmission in the central nervous system. One credits to these inhibitors the ability to contribute to improved levels of acetylcholine in the human body, on the other hand acetylcholine is a neurotransmitter and its presence in the organism is essential to maintenance and development human cognitive; it is believed that the absence of this neurotransmitter leads to dementia state, causing the known Alzheimer's disease. The selected drugs for this study were Tacrine, Donepezil, Rivastigmine, Galantamine and Physostigmine. For the implementation of the calculation we used the computer simulation software Conformers applied for the conformational calculations and for the other properties the DMol³. The properties were obtained for the lowest energy molecular structure for each molecule, It is possible to carry out study on the molecular orbitals HOMO and LUMO, density of state (PDOS), Besides the optical absorption spectra, infrared (IR) and Raman scattering. The calculated thermodynamic properties were entropy, enthalpy, free energy and the thermal capacity. All calculations were performed using functional LDA/PWC and GGA/PBE.

Background: Neurodegenerative diseases (NDD) are very common in the aging population, of which Parkinson’s disease (PD) and Alzheimer disease (AD) are the two most common. Since the etiology of the neuronal death in these diseases remains unclear, currently no curative therapy is available. Traditional Chinese medicine (TCM) has been used to treat certain diseases, which based on their symptoms we now know that they are included PD and AD, for thousands of years. However, our pervious systematic review reports that the quality of current TCM clinical trials related to this area had limited internal validity due to methodological flaws and insufficient data reporting. Methods: This study includes two add-on double-blinded randomized controlled trials (RCT), PD full-scale study and AD pilot study. It aims to provide evidence for the efficacy and safety of two specific TCM decoctions, Jia-Wei-Liu-Jun-Zi Tang (JWLJZT) and Di-tan decoction (DTD) in treating PD and AD, respectively. These clinical trials follow the Consolidated Standards of Reporting Trials (CONSORT) as well as the International Conference on Harmonization guidelines on Good Clinical Practice (GCP). Also, this two RCT obtained the approval from the Human and Animal Research Ethics Committee of Hong Kong Baptist University before the study and registered on the Chinese Clinical Trial Registry. Result: In the PD trial, 111 idiopathic PD patients were randomly assigned to receive either JWLJZT or placebo for 32 weeks. Although there was not significant difference in the primary outcome of Movement Disorder Society Sponsored Revision of Unified PD Rating Scale (MDS-UPDRS) Part I total score (p = 0.216), significant improvements was observed in the secondary outcome of Non-motor symptom assessment scale for Parkinson’s disease (NMSS) total score (p = 0.019), subtype of mood/cognition (p = 0.005) and hallucinations (p = 0.024). In addition, post-hoc analysis showed a significant reduction in constipation (p < 0.001). On the other hand, 40 AD patients were randomly assigned to receive either DTD or placebo for 24 weeks in the AD trial. There was an improvement trend in the primary outcome of the cognitive subscale of Alzheimer’s Disease Assessment Scale (ADAS-cog) total score in the DTD group though the difference relative to the placebo group was not statistically significant (p = 0.315). No significant difference was found in the secondary outcomes. Adverse events were mild and comparable between treatment and placebo groups in both trials. Discussion: JWLJZT did show some improvement in non-motor symptoms, including mood, cognition, and constipation, in PD patients, while, DTD did show a reducing trend in the cognitive impairment based on rigorous RCT. Further study focusing on the effective dosage, pharmacologic mechanism of JWLJZT and DTD are needed to give a fuller picture as well as better support for using them in human being as a routine treatment. In fact, JWLJZT and DTD are the only two examples of TCM for treating NDD. These two clinical trials are served as examples of how to evaluate efficacy and safety of TCM for the treatment of various diseases using rigorous RCT methods and standard. Keywords: Randomized Controlled Trials, Parkinson’s disease, Alzheimer disease, Traditional Chinese medicine, Jia-Wei-Liu-Jun-Zi Tang, Di-tan decoction, Efficacy, Safety

abstract: Alzheimer's Disease (AD) is a progressive neurodegenerative disease accounting for 50-80% of dementia cases in the country. This disease is characterized by the deposition of extracellular plaques occurring in regions of the brain important for cognitive function. A primary component of these plaques is the amyloid-beta protein. While a natively unfolded protein, amyloid-beta can misfold and aggregate generating a variety of different species including numerous different soluble oligomeric species some of which are precursors to the neurofibrillary plaques. Various of the soluble amyloid-beta oligomeric species have been shown to be toxic to cells and their presence may correlate with progression of AD. Current treatment options target the dementia symptoms, but there is no effective cure or alternative to delay the progression of the disease once it occurs. Amyloid-beta aggregates show up many years before symptoms develop, so detection of various amyloid-beta aggregate species has great promise as an early biomarker for AD. Therefore reagents that can selectively identify key early oligomeric amyloid-beta species have value both as potential diagnostics for early detection of AD and as well as therapeutics that selectively target only the toxic amyloid-beta aggregate species. Earlier work in the lab includes development of several different single chain antibody fragments (scFvs) against different oligomeric amyloid-beta species. This includes isolation of C6 scFv against human AD brain derived oligomeric amyloid-beta (Kasturirangan et al., 2013). This thesis furthers research in this direction by improving the yields and investigating the specificity of modified C6 scFv as a diagnostic for AD. It is motivated by experiments reporting low yields of the C6 scFv. We also used the C6T scFv to characterize the variation in concentration of this particular oligomeric amyloid-beta species with age in a triple transgenic AD mouse model. We also show that C6T can be used to differentiate between post-mortem human AD, Parkinson's disease (PD) and healthy human brain samples. These results indicate that C6T has potential value as a diagnostic tool for early detection of AD. / Dissertation/Thesis / M.S. Biological Design 2013

abstract: Alzheimer's disease (AD) is the most common type of dementia, affecting one in nine people age 65 and older. One of the most important neuropathological characteristics of Alzheimer's disease is the aggregation and deposition of the protein beta-amyloid. Beta-amyloid is produced by proteolytic processing of the Amyloid Precursor Protein (APP). Production of beta-amyloid from APP is increased when cells are subject to stress since both APP and beta-secretase are upregulated by stress. An increased beta-amyloid level promotes aggregation of beta-amyloid into toxic species which cause an increase in reactive oxygen species (ROS) and a decrease in cell viability. Therefore reducing beta-amyloid generation is a promising method to control cell damage following stress. The goal of this thesis was to test the effect of inhibiting beta-amyloid production inside stressed AD cell model. Hydrogen peroxide was used as stressing agent. Two treatments were used to inhibit beta-amyloid production, including iBSec1, an scFv designed to block beta-secretase site of APP, and DIA10D, a bispecific tandem scFv engineered to cleave alpha-secretase site of APP and block beta-secretase site of APP. iBSec1 treatment was added extracellularly while DIA10D was stably expressed inside cell using PSECTAG vector. Increase in reactive oxygen species and decrease in cell viability were observed after addition of hydrogen peroxide to AD cell model. The increase in stress induced toxicity caused by addition of hydrogen peroxide was dramatically decreased by simultaneously treating the cells with iBSec1 or DIA10D to block the increase in beta-amyloid levels resulting from the upregulation of APP and beta-secretase. / Dissertation/Thesis / M.S. Chemical Engineering 2014

O fenômeno qualidade de vida (QV) vem sendo amplamente estudado em ensaios clínicos e pesquisas científicas de doenças crônico-degenerativas e demências. Não há ainda disponível, em nossa cultura, um instrumento confiável e válido para avaliar QV nos quadros demenciais e, especificamente, na doença de Alzheimer (DA). O presente estudo tem por objetivos: avaliar as propriedades de medida da versão em Português da escala \"Quality of Life-AD (QOL-AD)\", avaliando a confiabilidade e a validade de constructo das três versões (PQdV, C-PQdV e CQdV) e também o impacto do comprometimento cognitivo sobre as propriedades de medida. A escala QOL-AD foi desenvolvida por Logsdon et al. em 1999. O instrumento é composto de 13 itens quantificados em uma escala de quatro pontos, sendo a pontuação 1 atribuída à qualificação ruim e a pontuação 4, à excelente. A pontuação total varia de 13 a 52, em que os índices mais altos indicam melhor QV. A escala possui três versões de avaliação de QV: o relato do paciente sobre sua QV (PQdV), o relato do cuidador/familiar sobre a QV do paciente (C-PQdV) e a versão do cuidador/familiar sobre sua própria QV (CQdV). A escala foi administrada a uma amostra de 60 pacientes com diagnóstico de DA provável, segundo os critérios do NINCDS-ADRDA, sendo 30 pacientes com grau leve e 30 pacientes com grau moderado de demência, segundo os critérios do DSM-III-R, e a seus respectivos cuidadores/familiares (n=60). A confiabilidade da escala foi avaliada através do alfa de Cronbach. Para a verificação da validade de constructo, as três versões da escala foram associadas às avaliações do funcionamento cognitivo, desempenho funcional, alterações de comportamento, sintomas depressivos e de nível socioeconômico e ao instrumento genérico de avaliação de QV (WHOQOL-breve). A confiabilidade da escala foi elevada, tanto para a versão do PQdV, como para a versão C-PQdV (alfa=0,80 e 0,83, respectivamente), quanto para a versão CQdV (alfa=0,86). Na validade de constructo da versão PQdV encontramos correlações significativas com: sintomas depressivos (GDS (-0,59, p<0,01) e Cornell (-0,49, p<0,01)), alterações de comportamento (-0,36, p<0,01) , com a questão número 1 (0,67, p<0,01) e o somatório do WHOQOL-breve (0,88, p<0,01). Na versão C-PQdV, foram encontradas correlações significativas com: comprometimento cognitivo (0,41, p<0,01), sintomas depressivos (GDS (-0,36, p<0,01) e Cornell (-0,68, p<0,01)), desempenho funcional (AIVDs (-0,52, p<0,01) e ABVDs (-0,51, p<0,01), alterações de comportamento (-0,71, p<0,01), com a questão número 1 (0,61, p<0,01) e o somatório do WHOQOL-breve (0,71, p<0,01). Na versão CQdV, as correlações encontradas foram com sintomas depressivos (Cornell (-0,30, p<0,05) e Inventário de depressão de Beck (-0,59 p<0,01)), alterações de comportamento (-0,39, p<0,01), desempenho funcional (AIVDs (-0,41, p<0,01) e ABVDs (-0,32, p<0,01),com a questão número 1 (0,55, p<0,01) e o somatório do WHOQOL-breve (0,81 p<0,01). A confiabilidade e a validade de constructo da escala foram mantidas independentemente do aumento da gravidade da doença. O gasto médio na aplicação da escala foi de aproximadamente seis minutos para cada uma das três versões. Os resultados indicam a confiabilidade e a validade constructo da versão em Português da escala de avaliação de QV na população estudada / The concept quality of life (QOL) has been extensively studied in clinical trials and in research of chronic-degenerative diseases and dementia. We do not have in our culture instruments available to evaluate QOL in dementia and, particularly, in Alzheimer\'s disease (AD). This study has the following objectives: to evaluate the psychometric properties of the Portuguese version of the scale, evaluating the reliability and construct validity of the three versions (PQdV, C-PQdV e CQdV), and the evaluation of the impact of cognitive performance on the psychometric properties. The scale \"Quality of Life-AD (QOL-AD)\" was developed by Logsdon et al. in 1999. The instrument is composed of 13 items quantified in a scale of four points, with the score 1 being attributed to the qualification poor and the score 4, to excellent. The total score varies from 13 to 52, with the highest indexes indicating better QOL. The scale has three versions of QOL evaluation: the QOL indexes from the patient\'s report on his/her own QOL (PQdV), the caregivers/family report on the patient\'s QOL (C-PQdV) and the version on QOL of the caregivers/family (CQdV). The scale was administered to a sample of 60 patients with diagnosis of probable AD, according to the NINCDS-ADRDA criteria, being 30 patients with mild dementia and 30 patients with moderate dementia, according to the DSM-III-R criteria, respectively, and to their caregivers/family members (n=60). The scale reliability was evaluated through Alfa\'s Cronbach. The construct validation was accomplished based on the correlations of the three scale versions with cognitive evaluation, functional performance, behavior disturbances, depressive symptoms and socioeconomic level and with a generic instrument of QOL (WHOQOL-brief). The scale reliability was high, both for the PQdV and for the C-PQdV version (alfa=0.80 and 0.83, respectively), as much as for the CQdV version (alfa=0.86). We observed significant correlations in the construct validity of PQdV version: with depressive symptoms (GDS (-0.59, p<0.01) and Cornell (-0.49, p<0.01)), behavior disturbances (-0.36, p<0.01), with the first item (0.67, p<0.01) and with the total score of WHOQOL-brief (0.88, p<0.01). We obtained significant correlations in the construct validity of the C-PQdV version: with cognitive impairment (0.41, p<0.01), depressive symptoms (GDS (-0.36, p<0.01) and Cornell (-0.68, p<0.01)), functional performance (AIVDs (-0.52, p<0.01) ABVDs (0.51, p<0.01), behavior disturbances (-0.71, p<0.01), with the first item (0.61, p<0.01) and with the total score of WHOQOL-brief (0.71, p<0.01). In the CQdV scale, the significant correlations were related to depressive symptoms (Cornell (-0.30, p<0.05) and Beck Depression Inventory (-0.59, p<0.01), behavior disturbances (-0.39, p<0.01), functional performance (AIVDs (-0.41, p<0.01) e ABVDs (-0.32, p<0.01), with the first item (0.55, p<0.01) and the total score of WHOQOL-brief (0.81, p<0.01). The scale reliability and construct validity were kept independently from the disease level. The scale took, on average, six minutes for each of the three versions. The results indicate reliability and construct validity of the Brazilian version of QOL-AD in the sample studied

A inclusão da eletroencefalografia nos protocolos de pesquisa diagnóstica para DA é plenamente justificada por sua larga disponibilidade, baixo custo, alta sensibilidade, o que possibilita a realização de exames seriados e o acompanhamento da evolução do estudo neurológico. Objetivo: Determinar um índice de corte, para utilizaçào na prática clínica, no auxilio diagnóstico da doença de Alzheimer. Metodologia: Avaliamos dois grupos de indivíduos compostos por 57 voluntários normais e idade superior a 50 anos comparados a 50 indivíduos com DA provável. Realizamos registros de EEG em vigília, olhos fechados e repouso por 30 minutos e computamos as potências espectrais das bandas de frequência alfa e teta, para todos os eletrodos, e calculamos a razão alfa/teta. Realizamos a regressão logística das variáveis razão alfa/teta da potência média do eletrodo C3 e do eletrodo O1e calculamos uma fórmula para o auxílio no diagnóstico da DA com um acerto cuja, sensibilidade para DA de 76, 4 % e especificidadede 84,6 % e a área sob a curva ROC 0.92. Conclusão: A regressão logística da razão alfa/teta do Espectro da potência média do EEG é um bom marcador para discriminar pacientes com doença de Alzheimer de controles normais / The inclusion of electroencephalography in diagnostic research protocols for AD is fully justified given EEG\'s wide availability, low cost and high sensitivity, allowing serial exams and neurological evolution follow-ups. Objective: To determine a screening index for use in routine clinical practice to aid the diagnosis of Alzheimer\'s disease. Methodology: Two groups of individuals older than 50 years, comprising a control group of 57 normal volunteers and a study group of 50 patients with probable AD, were compared. EEG recordings were performed of subjects in a wake state with eyes closed at rest for 30 mins. Spectral potentials of the alpha and theta bands were computed for all electrodes and the alpha/theta ratio calculated. Logistic regression of the variables alpha/theta of the mean potential of the C3 and O1 electrodes was carried out. A formula was calculated to aid the diagnosis of AD yielding 76.4 % sensitivity and 84.6 specificity for AD with an area under the ROC curve of 0.92. Conclusion: Logistic regression of the alpha/theta of the Spectrum of the mean potential of EEG represents a good marker for discriminating between AD patients and normal controls

Orientador: Monica Sanches Yassuda / Dissertação (mestrado) - Universidade Estadual de Campinas, Faculdade de Ciencias Medicas / Made available in DSpace on 2018-08-12T04:01:55Z (GMT). No. of bitstreams: 1 Aprahamian_Ivan_M.pdf: 2297167 bytes, checksum: 09e06865f4593ca514927b6569c04485 (MD5) Previous issue date: 2008 / Resumo: O Teste do Desenho do Relógio (TDR) é o segundo teste mais utilizado no mundo para o rastreio das demências. Contudo, há ainda dúvida sobre seu papel no processo diagnóstico da demência em termos de sensibilidade, especificidade, forma de aplicação e análise. OBJETIVOS: avaliar o desempenho do TDR no processo diagnóstico de uma amostra de idosos brasileiros portadores e não portadores da doença de Alzheimer (DA). Avaliar a sensibilidade (S) e a especificidade (E) do TDR, segundo as escalas de Shulman, Mendez e Sunderland, com as do Mini-Exame do Estado Mental (MEEM) e do Cambridge Cognitive Examination (CAMCOG), a bateria neuropsicométrica do Cambridge Examination for Mental Disorder of the Elderly (CAMDEX). METODOLOGIA: Estudo retrospectivo no qual foram analisados prontuários de pacientes idosos, 121 com DA e 99 controles normais, submetidos ao CAMDEX entre os anos de 2002 e 2007 dentro do Instituto de Geriatria e Gerontologia de Jundiaí seguindo protocolo padronizado. Todos os pacientes avaliados neste estudo passaram por avaliação médica detalhada anterior à realização do CAMDEX, incluindo exames laboratoriais e de neuroimagem. O CAMDEX apresenta duração média de duas horas, incluindo o CAMCOG, a bateria neuropsicométrica, que possui o MEEM e o TDR em sua avaliação. O TDR foi analisado separadamente utilizando-se três escalas comumente utilizadas na literatura (Shulman, Mendez e Sunderland). Os resultados do TDR foram comparados com os do CAMCOG e do MEEM. RESULTADOS: Encontrou-se correlação significativa entre os resultados do TDR com os do MEEM (0,700 - 0,730; p < 0,001) e do CAMCOG (0,753 - 0,779; p < 0,001). As três escalas de TDR utilizadas apresentam resultados semelhantes, sendo a melhor a escala de Shulman (S = 74,2 - 84,8%; E = 66,7 - 89,9%). A utilização conjunta do TDR com o MEEM melhora a sensibilidade e especificidade no rastreio cognitivo dos pacientes (S = 89,2 - 90%; E = 71,7 - 79,8%). Houve aumento da S e E do TDR com a baixa escolaridade. CONCLUSÃO: O TDR é um bom teste de rastreio quando comparado com o MEEM e o CAMCOG, independente da escala de interpretação utilizada. A combinação do TDR com o MEEM melhora seu rendimento. A influência da escolaridade merece estudo posterior. / Abstract: The Clock Drawing test (CDT) is the second most used test in the world for the screening of dementia. Although, there is still doubt over its paper in the diagnostic process of dementia in terms of sensitivity, specificity, application and interpretation. OBJECTIVES: evaluate the performance of the CDT in diagnostic process of a Brazilian elderly sample with and without Alzheimer's disease (AD). Evaluate the sensitivity (SE) and specificity (SP) of CDT, according to Shulman, Mendez and Sunderland, with the Mini-Mental State Examination (MMSE) and the Cambridge Cognitive Examination (CAMCOG), the neuropsychiatric battery of the Cambridge Examination for Mental Disorder of the Elderly (CAMDEX). METHODS: Retrospective study of 121 AD and 99 elderly controls medical charts that were submitted to the CAMDEX following a standardized protocol between 2002 and 2007 at the Jundiai's Geriatric and Gerontology Institute. All subjects were clinically evaluated and submitted to laboratory and neuroimaging studies. The CAMDEX has a mean time of two hours, including the CAMCOG, a neuropsychiatric battery that has the MMSE and the CDT in its evaluation. The CDT were analyzed separately using three common scales ((Shulman, Mendez and Sunderland). The results of the CDT were compared with the CAMCOG and the MMSE. RESULTS: There were significant correlation between the results of the CDT and the MMSE (0,700 - 0,730; p < 0,001) and between the CDT and the CAMCOG (0,753 - 0,779; p < 0,001). The three CDT scales showed similar results, but the Shulman's scales was slightly better (SE = 74,2 - 84,8%; SP = 66,7 - 89,9%). The combination between the CDT and the MMSE improved sensitivity and specificity in the cognitive screening of the subjects (SE = 89,2 - 90%; SP = 71,7 - 79,8%). There was improvement of sensitivity and specificity in patients with low level of formal education. CONCLUSION: The CDT is a good screening test when compared with the MMSE or the CAMCOG, independently of the scale used for its interpretation. The combination with the MMSE improves its performance significantly. The influence of education in the CDT deserves further studies. / Mestrado / Mestre em Gerontologia

Orientador: Edwiges Maria Morato / Tese (doutorado) - Universidade Estadual de Campinas, Instituto de Estudos da Linguagem / Made available in DSpace on 2018-08-19T02:06:38Z (GMT). No. of bitstreams: 1 Se_ElisandraVillelaGasparetto_D.pdf: 2855898 bytes, checksum: 8efcfb81974a59e1a91055b97c2af629 (MD5) Previous issue date: 2011 / Resumo: Esta pesquisa teve como objetivo estudar os processos de significação na interpretação de provérbios por sujeitos com provável doença de Alzheimer (DA) leve. Participaram da pesquisa qualitativa 10 sujeitos com idade igual ou superior a 60 anos com DA de ambos os sexos, que foram selecionados no Ambulatório de Psiquiatria Geriátrica do HC da UNICAMP. Esses sujeitos receberam diagnóstico de provável DA, a partir da avaliação clínica do médico e da avaliação neuropsicológica. Também foram considerados dados de um grupo controle composto por 10 sujeitos não-Alzheimer de perfil sociolinguístico semelhante ao da população com DA. O corpus desta pesquisa constituiu-se de dados obtidos da aplicação do Protocolo de Estudo de Provérbios elaborado por CAZELATO (2003) constituído de 10 provérbios considerados mais metafóricos e de 10 provérbios menos metafóricos. O procedimento metodológico consistiu em primeiro apresentar a cada sujeito os provérbios do Protocolo de forma oral e escrita, perguntando a ele "o que quer dizer tal provérbio". Num segundo momento, foi solicitado ao sujeito que "elaborasse ou imaginasse uma situação em que caberia o uso de tal provérbio". Os dados dos dois grupos foram gravados em vídeo e transcritos com base na notação de transcrição linguístico-interacional. A análise dos dados considerou o cotejamento dos dois grupos em relação ao trabalho linguístico-cognitivo requerido na manipulação enunciativa dos provérbios. Podemos apontar importantes questões em torno do funcionamento linguístico e cognitivo dos dois grupos de sujeitos estudados. Pudemos observar que ambas as populações procederam mais às interpretações centralmente relevantes e marginalmente relevantes frente aos provérbios mais e menos metafóricos, nos dois procedimentos do estudo. Entretanto, a população DA produziu maior número de interpretações literais. Quanto a isso, esta população não procedeu a interpretações irrelevantes do ponto de vista semântico-lexical, ainda que tais interpretações não tenham sido relevantes do ponto de vista pragmático. Foi possível verificar que ambos os grupos procederam à contextualização dos provérbios, imaginando uma situação de uso. Houve diferenças significativas no percurso enunciativo-discursivo realizado pelos sujeitos não-Alzheimer e pelos Alzheimer. Os sujeitos não-Alzheimer recorreram mais às exemplificações de situações cotidianas de uso dos provérbios e recorreram mais a expedientes linguísticos e textuais para proceder à interpretação, tais como modalizações epistêmicas e marcadores de relações espaço-temporais, fazendo ainda comparações temporais do uso do provérbio, utilizando indicadores de relações lógico-semânticas (condicionalidade, finalidade, causalidade), articuladores argumentativos (evidenciados nas ações reflexivas e metaenunciativas). As interpretações consideradas irrelevantes ocorreram com menor frequência. Quanto às estratégias linguístico-discursivas empregadas pelos sujeitos, verificou-se uma maior ocorrência entre os sujeitos com DA de autorrepetição, de reflexão em voz alta, de hesitação, de pausas não preenchidas, de repetição hesitante, de reformulação, de indagação, de falsos inícios de turno e de retomadas. Todos esses fenômenos, típicos do processamento online da língua falada, indicam movimentos do papel organizador e estruturador da linguagem. Esta pesquisa torna-se relevante para qualificar o processo linguístico-cognitivo implicado na significação, notadamente na construção de sentidos indiretos e da referenciação no contexto neurolinguístico. Isso é particularmente importante para melhor compreendermos a natureza sócio-cognitiva da linguagem no contexto das neurodegenerescências / Abstract: The aim of this research was to study the signification processes in the interpretation of proverbs by subjects with probable mild Alzheimer's disease (AD). 10 subjects 60 years or older of both genders with AD participated of the qualitative research. They were selected in the Clinic of Geriatric Psychiatry, of Faculty of Medicine - HC - UNICAMP. These subjects were diagnosed with probable AD from the doctor's clinical examination and neuropsychological examination. Data from a control group of 10 non-Alzheimer subjects of sociolinguistic profile similar to that of people with AD were also considered. The corpus of this research was composed of data obtained from the application of the Protocol for the Proverbs Study written by CAZELATO (2003) which consisted of 10 proverbs considered more metaphorical and 10 considered less metaphorical. The methodological procedure consisted in first presenting the Protocol proverbs in verbal and writing forms to each subject, asking him "what means such proverb". Secondly, the subject was asked to "prepare or imagine a situation in which the use of such proverb would fit". The data from both groups were video-recorded and transcribed based on the linguistic-interactional transcript notation. The data analysis considered the comparison of both groups in relation to the cognitive-linguistic work required in proverbs enunciative manipulation. We can indicate important issues concerning to language and cognitive functioning of both groups of subjects studied. We could also note that both populations made more to the centrally relevant and marginally relevant interpretations concerning the more and less metaphorical proverbs in both study procedures. However, the AD population produced more literal interpretations. In regard to that, this population has not made irrelevant interpretations in terms of lexicon and semantics, even though such interpretations have not been relevant from the pragmatic point of view. It was possible to verify that both groups contextualized the proverbs, imagining a situation of use. There were meaningful differences in enunciative-discursive course performed by non-Alzheimer's and Alzheimer's subjects. The non-Alzheimer's subjects evoked more exemplifying everyday situations of use of proverbs and remembered more linguistic and textual expedients to make the interpretation, such as epistemic modalities and markers of space-time relations. They also made temporal comparisons in the use of the proverb using indicators of logical-semantic relations (conditionality, purpose, causality), argumentative articulators (evident in the reflexive and meta-enunciative actions). Interpretations considered irrelevant occurred less frequently. As for the linguistic-discursive strategies applied by the subjects, it was noticed among individuals with AD a most frequent occurrence of auto-repetition, of thinking aloud, of hesitation, of unfilled pauses, of hesitant repetition, of reformulation, of quest, of false beginning of shifts and of retaking. All these phenomena, typical of the online processing of spoken language, indicate movements of the leading and structuring role of the language. This research becomes relevant to qualify the cognitive-linguistic process involved in the significance, especially in the construction of indirect meanings and of referenciation in the neurolinguistic context. This is particularly important to better understand the socio-cognitive nature of language, specifically in the context of neurodegeneration / Doutorado / Linguistica / Doutor em Linguística

Kyoto University (京都大学) / 0048 / 新制・課程博士 / 博士(農学) / 甲第18328号 / 農博第2053号 / 新制||農||1022(附属図書館) / 学位論文||H26||N4835(農学部図書室) / 31186 / 京都大学大学院農学研究科食品生物科学専攻 / (主査)教授 入江 一浩, 教授 河田 照雄, 教授 保川 清 / 学位規則第4条第1項該当