Introdução: segundo a literatura, sais de lítio podem produzir redução da função renal. A magnitude dessa informação é debatível, uma vez que não há estudo clínico randomizado e controlado entre usuários de lítio, em sua maioria pacientes com depressão ou transtorno bipolar. A possibilidade do uso do lítio para o tratamento da demência de Alzheimer prodrômica reforça a necessidade de maior investigação de efeitos adversos atribuídos ao lítio, especialmente com relação à função renal. Objetivos: avaliar a segurança da utilização do lítio em baixa dosagem com relação à função renal de pacientes idosos. Como objetivos secundários serão avaliadas: a segurança clínica através de exame e questionário específico, as funções tireoidiana, imunológica e o metabolismo glicêmico. Métodos: estudo randomizado e placebo controlado de 2 anos, seguido de fase aberta por mais 2 anos. Foram avaliados 59 idosos com comprometimento cognitivo leve com seguimento mínimo de dois anos (fase controlada). A função renal foi estimada através das fórmulas aMDRD e CKD- EPI, a partir de exames laboratoriais e dados clínicos coletados durante o estudo. As funções tireoidiana, imunológica e glicêmica foram avaliadas respectivamente através de TSH, T4 livre, leucócitos total, neutrófilos, linfócitos, glicemia e insulinemia de jejum, e HOMA-IR. A segurança clínica foi avaliada através de entrevista sistemática realizada a cada 3 meses, utilizando exame físico e a escala UKU para efeitos adversos. Resultados: não houve piora da função renal com o uso do lítio (litemia entre 0,25-0,5 mmol/l) tanto pela aMDRD (p=0,453) como pela CKD-EPI (p=0,181). Houve aumento significativo de neutrófilos (p=0,038) e do TSH (p=0,034). O grupo lítio apresentou incidência significativamente maior de diabetes mellitus (p=0,037) e arritmias (p=0,028), maior ganho de peso (p=0,015), mais sintomas na escala UKU (p=0,045), e maior interferência dos efeitos adversos do lítio em atividades diárias (p<0,001). Houve correlação entre a opinião de médico e do paciente nas interferências das atividades diárias atribuídas aos sintomas adversos (p<0,001). Conclusões: o uso de lítio em baixa dose não alterou a função renal, produziu alterações no sistema imunológico e tireoidiano sem impacto clínico, e foi seguro clinicamente. As razões do aumento de incidência de diabetes e arritmias merecem investigação posterior / Introduction: according to the literature, lithium salts may produce a reduction in kidney function. The magnitude of this information is debatable because there is no randomized and controlled clinical trial among lithium users, being mostly patients with depression or bipolar disorder. The possibility of using lithium for the treatment of prodromal Alzheimer\'s disease dementia increases the need for further investigation of adverse effects attributed to lithium, especially regarding to renal function. Objectives: To evaluate the safety of using low-dose lithium with respect to renal function in elderly patients. Secondary objectives were the evaluation of the clinical safety through specific questionnaire and clinical assessment, and to assess thyroid, immunological and glycemic function. Methods: a randomized and placebo controlled study for 2 years, followed by an open label follow-up of 2 years. We evaluated 59 elderly patients with mild cognitive impairment with accomplishment of at least two years of the controlled phase. Renal function was estimated by the aMDRD and CKD-EPI equation, and by laboratory and clinical data collected during the trial. The thyroid, immunological and glycemic functions were respectively evaluated by TSH, free T4, leukocyte count, neutrophil count, lymphocyte count, fasting plasma glucose and insulin, and the HOMA-IR. The clinical safety was evaluated through systematic examination performed every 3 months, with physical examination, clinical interview and UKU scale for adverse effects. Results: There was no decline of renal function with the use of lithium (litemia between 0.25-0.5 mmol/l) both in the aMDRD (p=0.453) and CKD-EPI (p=0.181) equations. A significant increase of neutrophils (p=0.038) and TSH (p=0.034) were observed. The lithium group showed significantly higher incidence of diabetes mellitus (p=0.037), arrhythmias (p=0.028), weight gain (p=0.015), more symptoms of UKU scale (p=0.045), and greater interference from the adverse effects of lithium during daily activities (p<0.001). There was an observed correlation between the opinion of the attending physician and the patient in respect to the interference in daily activities secondary to the adverse symptoms (p<0.001). Conclusions: The use of lithium in low doses did not result in renal function impairment, produced subtle changes in the immunological system and thyroid function, and was clinically safe for adverse effects. The reasons for the increased incidence of arrhythmias and diabetes mellitus deserve further investigation

O presente estudo consistiu-se na avaliação clínica e aplicação de testes cognitivos, além da realização de ressonância magnética (RM), de 3 tesla, do cérebro, processada com a técnica de \"Voxel-based Morphometry\" (VBM) e \"Skull Strip\", e 18F-FDG PET -CT processado com \"Statistical Parametric Mapping\" (SPM8) e correção de volume parcial (PVELab), em idosos sem déficits cognitivos (CDR=0), com comprometimento cognitivo leve amnéstico (CCL) (CDR=0,5) e com Doença de Alzheimer leve (DA leve)(CDR de 0,5 a 1). Os objetivos foram comparar os padrões de neuroimagem estrutural e metabólica entre os grupos, assim como correlacionar alterações estruturais volumétricas da RM e alterações metabólicas cerebrais do PET-CT, a um teste funcional, o \"Informant Questionnaire on Cognitive Decline in the Elderly\" (IQCODE), nessa mesma amostra. Cada um dos grupo 3 grupos, pareados por idade, contém 30 indivíduos, totalizando amostra de 90. Os resultados dos exames de Neuroimagens, divididos por comparações entre os grupos, e corrigidos pela escolaridade, foram considerados significativos todos os achados nos quais a significância corrigida for <= 0,05 (p-FWEcorr <= 0,05). No CCL x DA foi observado hipometabolismo Giro do Cíngulo à Direita. No grupo DA x CCL foram observados hipometabolismos no Giro do Cíngulo à Esquerda, no Precuneus Esquerdo, Precuneus Direito e na parte inferior do Lobo Parietal Esquerdo. Na DA x Controle, utilizando-se pesquisa de área a priori e filtros gaussiano de 8mm e 4mm, foi observada redução estatisticamente significante quanto ao volume de substância cinzenta na Amígdala Esquerda e na Amígdala Direita. No PET - CT, da DA, em relação ao grupo controle foram observadas áreas de hipometabolismos no Giro do Cíngulo à Esquerda, no Precuneus Direito e no Giro Temporal Medial Direito. Na correlação direta do IQCODE, na comparação DA x Controle, no PET - CT evidenciou-se hipometabolismo no Giro Fusiforme Direito. Em conclusão, os resultados das comparações entre os grupos foram semelhantes ao encontrado na literatura para fases iniciais (leves) da patologia e mostraram, ainda, uma tendência a um \"continuum\" do controle até a DA. Por outro lado à correlação do IQCODE no DA x Controle carece de comprovação por outros trabalhos e com outros constructos estatísticos / This study consisted in the clinical evaluation and application of cognitive tests, in addition to magnetic resonance imaging (MRI) of 3 Tesla, of brain, processed with the technique of \"Voxel-based Morphometry\" (VBM) and \"Skull Strip\", and 18F-FDG PET-CT processed by \"Statistical Parametric Mapping\" (SPM8) and partial volume correction (PVELab) in subjects without cognitive impairment (CDR = 0), with amnestic mild cognitive impairment (MCI)(CDR = 0.5) and with mild Alzheimer \'s disease (AD mild)(CDRs of 0.5 to 1). The objectives were to compare the patterns of structural and metabolic neuroimaging between groups, as well as correlate MRI\'s volumetric structural changes and PET-CT\'s metabolic brain with a functional test, the \"Informant Questionnaire on Cognitive Decline in the Elderly\" (IQCODE) in this same sample. Each one of three groups, matched by age, contains 30 subjects, totaling 90. The test results of neuroimaging, divided by comparisons between groups, and corrected by education, were considered significant the findings that corrected significance is <= 0.05 (p-FWEcorr <= 0.05). In CCL x DA was observed hypometabolism right cingulate gyrus. In DA x CCL hypometabolism were observed in the left cingulate gyrus, the left precuneus, right precuneus and left inferior parietal lobe. In DA x Control, using the \"a priori\" research area and gaussian filters 8mm and 4mm was observed statistically significant reduction on the volume of gray matter in the left and right amygdala. In PET - CT of DA relative to control group were observed areas of hypometabolisms in left cingulate, right precuneus and in the right medial temporal gyrus. In direct correlation of the IQCODE, compared DA x Control on PET - CT revealed a hypometabolism in the right fusiform gyrus. In conclusion, the results of the comparisons between groups were similar to those found in the literature for early (mild) pathology and showed a \"continuum\" of control to the DA. On the other hand the correlation of the IQCODE in DA x Control lacks confirmation by other studies and other statistical constructs

O presente estudo consistiu-se na avaliação clínica e aplicação de testes cognitivos, além da realização de ressonância magnética (RM), de 3 tesla, do cérebro, processada com a técnica de \"Voxel-based Morphometry\" (VBM) e \"Skull Strip\", e 18F-FDG PET -CT processado com \"Statistical Parametric Mapping\" (SPM8) e correção de volume parcial (PVELab), em idosos sem déficits cognitivos (CDR=0), com comprometimento cognitivo leve amnéstico (CCL) (CDR=0,5) e com Doença de Alzheimer leve (DA leve)(CDR de 0,5 a 1). Os objetivos foram comparar os padrões de neuroimagem estrutural e metabólica entre os grupos, assim como correlacionar alterações estruturais volumétricas da RM e alterações metabólicas cerebrais do PET-CT, a um teste funcional, o \"Informant Questionnaire on Cognitive Decline in the Elderly\" (IQCODE), nessa mesma amostra. Cada um dos grupo 3 grupos, pareados por idade, contém 30 indivíduos, totalizando amostra de 90. Os resultados dos exames de Neuroimagens, divididos por comparações entre os grupos, e corrigidos pela escolaridade, foram considerados significativos todos os achados nos quais a significância corrigida for <= 0,05 (p-FWEcorr <= 0,05). No CCL x DA foi observado hipometabolismo Giro do Cíngulo à Direita. No grupo DA x CCL foram observados hipometabolismos no Giro do Cíngulo à Esquerda, no Precuneus Esquerdo, Precuneus Direito e na parte inferior do Lobo Parietal Esquerdo. Na DA x Controle, utilizando-se pesquisa de área a priori e filtros gaussiano de 8mm e 4mm, foi observada redução estatisticamente significante quanto ao volume de substância cinzenta na Amígdala Esquerda e na Amígdala Direita. No PET - CT, da DA, em relação ao grupo controle foram observadas áreas de hipometabolismos no Giro do Cíngulo à Esquerda, no Precuneus Direito e no Giro Temporal Medial Direito. Na correlação direta do IQCODE, na comparação DA x Controle, no PET - CT evidenciou-se hipometabolismo no Giro Fusiforme Direito. Em conclusão, os resultados das comparações entre os grupos foram semelhantes ao encontrado na literatura para fases iniciais (leves) da patologia e mostraram, ainda, uma tendência a um \"continuum\" do controle até a DA. Por outro lado à correlação do IQCODE no DA x Controle carece de comprovação por outros trabalhos e com outros constructos estatísticos / This study consisted in the clinical evaluation and application of cognitive tests, in addition to magnetic resonance imaging (MRI) of 3 Tesla, of brain, processed with the technique of \"Voxel-based Morphometry\" (VBM) and \"Skull Strip\", and 18F-FDG PET-CT processed by \"Statistical Parametric Mapping\" (SPM8) and partial volume correction (PVELab) in subjects without cognitive impairment (CDR = 0), with amnestic mild cognitive impairment (MCI)(CDR = 0.5) and with mild Alzheimer \'s disease (AD mild)(CDRs of 0.5 to 1). The objectives were to compare the patterns of structural and metabolic neuroimaging between groups, as well as correlate MRI\'s volumetric structural changes and PET-CT\'s metabolic brain with a functional test, the \"Informant Questionnaire on Cognitive Decline in the Elderly\" (IQCODE) in this same sample. Each one of three groups, matched by age, contains 30 subjects, totaling 90. The test results of neuroimaging, divided by comparisons between groups, and corrected by education, were considered significant the findings that corrected significance is <= 0.05 (p-FWEcorr <= 0.05). In CCL x DA was observed hypometabolism right cingulate gyrus. In DA x CCL hypometabolism were observed in the left cingulate gyrus, the left precuneus, right precuneus and left inferior parietal lobe. In DA x Control, using the \"a priori\" research area and gaussian filters 8mm and 4mm was observed statistically significant reduction on the volume of gray matter in the left and right amygdala. In PET - CT of DA relative to control group were observed areas of hypometabolisms in left cingulate, right precuneus and in the right medial temporal gyrus. In direct correlation of the IQCODE, compared DA x Control on PET - CT revealed a hypometabolism in the right fusiform gyrus. In conclusion, the results of the comparisons between groups were similar to those found in the literature for early (mild) pathology and showed a \"continuum\" of control to the DA. On the other hand the correlation of the IQCODE in DA x Control lacks confirmation by other studies and other statistical constructs

Σκοπός είναι να ερευνηθεί αν οι μετρήσεις του Πάχος του Ενδοθηλίου των Κοινών Καρωτίδων (ΠΕΚΚΑ) σε ασθενείς με Αγγειακό Εγκεφαλικό Επεισόδιο (ΑΕΕ) σχετίζονται με την άμεση ή μακροπρόθεση έκβαση του ΑΕΕ, με την μελλοντική εμφάνιση νοητικής έκπτωσης ή κατάθλιψης και με την υποτροπή του ΑΕΕ. ΜΕΘΟΔΟΙ: 284 ασθενείς με πρώτο ισχαιμικό ΑΕΕ που υποβλήθηκαν σε υπερηχογραφική μέτρηση του ΠΕΚΚΑ στην οξεία φάση, παρακολουθήθηκαν για ένα χρόνο. Η άμεση έκβαση εκτιμήθηκε κατά την έξοδο, ενώ η μακροπρόθεσμη έκβαση, η νοητική και συναισθηματική κατάσταση εκτιμήθηκαν μετά από 12 μήνες. Επίσης καταγράφηκαν οι υποτροπές στη διάρκεια του πρώτου χρόνου. ΑΠΟΤΕΛΕΣΜΑΤΑ: το ΠΕΚΚΑ δε συσχετιζόταν με την άμεση ή μακροπρόθεσμη έκβαση του ΑΕΕ ούτε με την ύπαρξη κατάθλιψης ένα χρόνο αργότερα. Αντίθετα, αυξημένες τιμές ΠΕΚΚΑ σχετίζονταν σημαντικά και ανεξάρτητα τόσο με την ύπαρξη νοητικής έκπτωσης 12 μήνες αργότερα όσο και με τoν κίνδυνο υποτροπής του ΑΕΕ κατά τη διάρκεια του πρώτου χρόνου. ΣΥΜΠΕΡΑΣΜΑ: οι μετρήσεις του ΠΕΚΚΑ αμέσως μετά από ισχαιμικό ΑΕΕ μπορεί να χρησιμεύουν στην αναγνώριση ασθενών με αυξημένο κίνδυνο για μελλοντική νοητική έκπτωση ή υποτροπή του ΑΕΕ. / Thesis objective is to investigate whether the measurements of Common Carotid Artery Intima Media Thickness (CCA-imt) in patients with acute stroke are associated with the stroke outcome, either short term or long term, with the future development of post stroke cognitive impairment and post stroke depression and with stroke recurrences within the first year after the stroke. METHODS: 284 consequent patients with first ever ischaemic stroke that underwent carotid ultrasonographic measurement of CCA-imt in the acute phase, were followed-up for one year. The short-term outcome was assessed at discharge. The long-term outcome and the presence of cognitive impairment and depressive symptoms were assessed 12 months later. The number of recurrences within the first year was also recorded. RESULTS: CCA-imt values were not associated with the short- or long-term stroke outcome or the presence of depression one year after the ictus. On the contrary, increased CCA-imt values were significantly and independently associated with cognitive impairment and with the risk of recurrence during the first year. CONCLUSION: measurements of CCA-imt right in the acute phase after an ischaemic stroke can help with the identification of patients in higher risk for future cognitive impairment and stroke recurrence.

Inledning: Äldre personer med kognitiv svikt, exempelvis i form av demenssjukdom, delirium eller depression, är en vanligt förekommande population inom svensk sjukhusvård. Dessa äldre kan ha särskilda behov till följd av en försämrad kognition, men litteraturen tyder på att akutsjukhusens miljö, organisation och vårdprocesser inte alltid stödjer tillgodoseendet av dessa behov. Syfte: Det övergripande syftet med avhandlingen var att belysa vården av äldre personer med kognitiv svikt i sjukhusmiljöer. Metoder: Avhandlingen består av fyra delstudie. I studie I tillämpades en tvärsnittsdesign för att utforska personalens attityder till äldre patienter med kognitiv svikt, personalens tillfredsställelse med vården och arbetet samt upplevelsen av personcentrerat vårdklimat (n=391). I studie II användes en Grounded theory design för att undersöka hinder för personcentrerad vård för äldre personer med kognitiv svikt på en akutmedicinsk vårdavdelning. I studie III tillämpades en tvärsnittsdesign för att utforska de psykometriska egenskaperna i den svenska versionen av ”The Person-centred care of Older People with cognitive impairment in Acute Care scale” (POPAC) i ett urval av sjukhuspersonal (n=293). I studie IV användes en fenomenologisk hermeneutisk design för att belysa innebörder av att vårda äldre patienter med kognitiv svikt på akuta sjukvårdavdelningar utifrån vårdpersonals (n=13) berättelser. Resultat: Studie I visade att deltagande personal skattade en neutral attityd till äldre patienter med kognitiv svikt i spektret mellan negativa och positiva attityder, samt att faktorer som att vara yngre, undersköterska och att uppleva vården av de äldre som betungande, hade samband med mer negativa attityder. Resultaten visade också att vårdpersonal upplevde att äldre patienters kognition sällan utvärderades under vårdtiden, samt att man sällan baserade vården på evidensbaserade riktlinjer för vård av äldre med kognitiv svikt. Studie II belyste att ett organisatoriskt fokus på medicinska behov, åtgärder och rutiner bidrog till att personal hamnade steget efter i relation till att synliggöra och möta dessa äldre personers multidimensionella behov, och att detta kunde medföra tecken på vårdlidande för de äldre, utanförskap för närstående och frustration för personal. Studie III stödde en fortsatt användning av POPAC-skalan för skattningar av upplevd förekomst av personcentrerade vårdprocesser för äldre patienter med kognitiv svikt, men att ytterligare studier rekommenderades framförallt av skalans olika dimensioner. Studie IV belyste att ju större avstånd som upplevs mellan vad vårdpersonalen kan göra (verklig vård) och vad de vill göra (ideal vård) för äldre patienter med kognitiv svikt i akuta vårdmiljöer, desto meningslösare upplevs vården, och desto större blir hotet mot personalens personlig-professionella integritet. Den tolkade helheten visar på att vårda äldre patienter med kognitiv svikt inom akutsjukvård betyder att försöka ge omvårdnad i miljöer som inte stödjer vårdpersonalens personlig-professionella integritet Slutsatser: En rimlig konklusion av dessa resultat är att det i sjukhusmiljöer där äldre patienter ofta vårdas kan finnas anledning att diskutera och ytterligare studera hur attityder, synsätt på och målsättningar för vården och dess innehåll, åtgärder och interventioner kan främja eller motverka en god omvårdnad för de äldre med kognitiv svikt. Det kan också finnas anledning att se över hur personalen kan stödjas i att ge person-centrerad vård till de äldre, exempelvis genom riktlinjer för vård av äldre personer med kognitiv svikt, standardiserade skattningar av kognition, samt implementering av vårdprocesser som stödjer en personcentrerad vård för dessa patienter. Det kan också finnas behov av att ytterligare kritiskt granska hur organisatoriska och miljömässiga faktorer på avdelningar stödjer eller motverkar en personcentrerad vård för äldre patienter med kognitiv svikt. Därtill kan det finnas behov av att skapa ytterligare förutsättningar för vårdpersonalen att bevara och utveckla sin personlig-professionella integritet genom att utveckla miljöer som ger möjligheter för dem att ge en god omvårdnad till dessa äldre. / Introduction: Older people with cognitive impairment such as dementia, delirium or depression, are commonly cared for in acute hospital wards. These older people may have specific needs associated with a cognitive impairment. However, literature indicates that the milieu, organisation and care processes in acute care not always support in meeting these needs. Aim: The overall aim of the thesis was to illuminate care of older people with cognitive impairment in hospital environments. Methods: The thesis consists of four studies. Study I used a cross-sectional design to explore staff attitudes toward older people with cognitive impairment, staff satisfaction with care and work and perceived person-centeredness of the ward (n=391). Study II used a Grounded theory design to explore barriers to person-centred care for older people with cognitive impairment at an acute medical ward. Study III used a cross-sectional design to explore the psychometric properties of the Swedish version person-centred care for older people with cognitive impairment scale (POPAC) in a sample of acute hospital staff (n=293). Study IV used a phenomenological hermeneutic design to explore the meanings of caring for older people with cognitive impairment in acute hospital wards as narrated by nursing staff (n=13). Results: Study I showed that participating staff estimated a neutral attitude to older people with cognitive impairment in the spectrum between negative and positive attitudes, and that factors such as being younger, a nurse assistant and experiencing the care of older people with cognitive impairment as burdensome, were associated with more negative attitudes. The results also showed that healthcare professionals felt that older patients' cognitive ability was rarely evaluated during hospitalisation, and that care were rarely based on evidence-based guidelines for care of older people with cognitive impairment. Study II illuminated that an organizational focus on medical needs, interventions and routines contributed to staff falling behind in relation to meeting these older patients' multidimensional needs, and that this could lead to signs of suffering for older patients, feelings of being excluded for relatives, and a frustration for staff. Study III supported a continued use of the POPAC scale for ratings of perceived prevalence of person-centred care processes for older people with cognitive impairment, but further studies was recommended to explore scale dimensionality. Study IV illuminated that the greater a gap that is experienced between what nurses can do (real) and what they want to do (ideal) in caring for older patients with cognitive impairment in acute care settings, the more meaningless care is experienced and the greater a threat is experienced to the nurses personal-professional integrity. The comprehensive understanding indicated that caring for older people with cognitive impairment in acute care settings means to provide nursing care in an environment that does not support the nurses’ possibilities to protect and develop their personal-professional integrity. Conclusions: A reasonable conclusion from these studies is that there may be reasons to further discuss and study how attitudes, perspectives, and goals for care, together with the content, procedures and interventions that can support or obstruct good nursing care for older people with cognitive impairment in hospital settings. There may also be reasons to explore how staff can be supported to provide person-centred care to these older patients, for example through guidelines for care of older people with cognitive impairment, standardised assessments of cognitive ability, and implementation of care processes that supports person-centred care. In addition, to further critically examine how organisational and environmental factors in hospital wards can support or obstruct person-centred care for older patients seems needed. There may also be a need to further develop conditions that can support nursing staff to maintain and develop their personal-professional integrity, by developing environments that provides further possibilities to provide good care for these older patients. / <p>Centrum för personcentrerad vård vid Göteborgs universitet </p>

Orientador: Gabriela Castellano / Tese (doutorado) - Universidade Estadual de Campinas, Instituto de Fisica Gleb Wataghin / Made available in DSpace on 2018-08-15T22:34:24Z (GMT). No. of bitstreams: 1 Oliveira_MarciaSilvade_D.pdf: 17533323 bytes, checksum: 32a83eb4815b68f061baa91a4b0ab2e4 (MD5) Previous issue date: 2010 / Resumo: Análise de textura em imagens digitais é um termo que se refere a um grupo de técnicas de processamento de imagens que objetivam a extração de descritores da imagem ou de regiões de interesse (ROIs) de forma a simplificar a caracterização das mesmas. A textura pode ser entendida como características intrínsecas da imagem (por exemplo: brilho, cor e distribuição de formas) que remetem à ideia de regularidade, rugosidade, suavidade, entre outras, por isso o nome 'textura'. Um tipo particular de análise de textura, bastante utilizado em imagens médicas, se baseia em medidas estatítsticas relativas à distribuição de níveis de cinza da imagem (matriz de coocorrência). Os descritores de textura, baseados na matriz de coocorrência, são conhecidos como descritores de Haralick. Este trabalho consistiu na aplicação de vídeo deste tipo de análise em imagens de Tomografia Computadorizada (TC) de vítimas de Acidente Vascular Cerebral Isquêmico e em imagens de Ressonância Magnetica (RM) de portadores de Epilepsia Mioclônica Juvenil, Doença de Machado-Joseph, Déficit Cognitivo Leve e Doença de Alzheimer, visando o desenvolvimento de uma ferramenta computacional que auxilie o neurologista na identificação de areas atingidas por estas doenças e que não sejam distinguíveis em uma análise visual. Neste trabalho foram selecionadas regiões de interesse (ROIs) e calculados os parâmetros de textura para cada grupo de imagens. Após o cálculo dos descritores de textura foi realizada uma análise estatística para verificar se havia diferenciação entre os vários tipos de tecidos. Os resultados obtidos mostraram que a análise de textura pode, de fato, ser utilizada para a extração de características discriminantes, tanto nas imagens de TC quanto nas imagens de RM para as cinco patologias analisadas / Abstract: Texture analysis in digital images is a term that refers to a group of image processing techniques that aim to extract descriptors of the image or regions of interest (ROIs) in order to simplify their characterization. Texture may be understood as intrinsic characteristics of the image (such as brightness, color and distribution of forms) that refer to the idea of regularity, roughness and smoothness, hence the name 'texture'. A particular type of texture analysis, widely used in medical imaging, is based on statistical measurements related to the image gray level distribution (coocurrence matrix). The texture descriptors based on the coocurrence matrix are known as Haralick descriptors. This work consisted on applying this type of analysis to computed tomography (CT) images of victims of Ischemic Stroke and magnetic resonance images (MRI) of patients with Juvenile Myoclonic Epilepsy, Machado-Joseph disease, mild cognitive impairment and Alzheimer's disease, in order to develop a computational tool to assist neurologists in the identification of areas affected by these diseases and which are not perceived in a visual analysis. In this work we selected regions of interest (ROIs) and calculated the texture parameters for each group of images. After the calculation of the texture descriptors, a statistical analysis was performed to determine whether there was differentiation between the various types of tissues. The results showed that texture analysis can indeed be used for the extraction of discriminant features in both the CT an the MR images for the five studied pathologies / Doutorado / Física / Doutora em Ciências

Introdução: segundo a literatura, sais de lítio podem produzir redução da função renal. A magnitude dessa informação é debatível, uma vez que não há estudo clínico randomizado e controlado entre usuários de lítio, em sua maioria pacientes com depressão ou transtorno bipolar. A possibilidade do uso do lítio para o tratamento da demência de Alzheimer prodrômica reforça a necessidade de maior investigação de efeitos adversos atribuídos ao lítio, especialmente com relação à função renal. Objetivos: avaliar a segurança da utilização do lítio em baixa dosagem com relação à função renal de pacientes idosos. Como objetivos secundários serão avaliadas: a segurança clínica através de exame e questionário específico, as funções tireoidiana, imunológica e o metabolismo glicêmico. Métodos: estudo randomizado e placebo controlado de 2 anos, seguido de fase aberta por mais 2 anos. Foram avaliados 59 idosos com comprometimento cognitivo leve com seguimento mínimo de dois anos (fase controlada). A função renal foi estimada através das fórmulas aMDRD e CKD- EPI, a partir de exames laboratoriais e dados clínicos coletados durante o estudo. As funções tireoidiana, imunológica e glicêmica foram avaliadas respectivamente através de TSH, T4 livre, leucócitos total, neutrófilos, linfócitos, glicemia e insulinemia de jejum, e HOMA-IR. A segurança clínica foi avaliada através de entrevista sistemática realizada a cada 3 meses, utilizando exame físico e a escala UKU para efeitos adversos. Resultados: não houve piora da função renal com o uso do lítio (litemia entre 0,25-0,5 mmol/l) tanto pela aMDRD (p=0,453) como pela CKD-EPI (p=0,181). Houve aumento significativo de neutrófilos (p=0,038) e do TSH (p=0,034). O grupo lítio apresentou incidência significativamente maior de diabetes mellitus (p=0,037) e arritmias (p=0,028), maior ganho de peso (p=0,015), mais sintomas na escala UKU (p=0,045), e maior interferência dos efeitos adversos do lítio em atividades diárias (p<0,001). Houve correlação entre a opinião de médico e do paciente nas interferências das atividades diárias atribuídas aos sintomas adversos (p<0,001). Conclusões: o uso de lítio em baixa dose não alterou a função renal, produziu alterações no sistema imunológico e tireoidiano sem impacto clínico, e foi seguro clinicamente. As razões do aumento de incidência de diabetes e arritmias merecem investigação posterior / Introduction: according to the literature, lithium salts may produce a reduction in kidney function. The magnitude of this information is debatable because there is no randomized and controlled clinical trial among lithium users, being mostly patients with depression or bipolar disorder. The possibility of using lithium for the treatment of prodromal Alzheimer\'s disease dementia increases the need for further investigation of adverse effects attributed to lithium, especially regarding to renal function. Objectives: To evaluate the safety of using low-dose lithium with respect to renal function in elderly patients. Secondary objectives were the evaluation of the clinical safety through specific questionnaire and clinical assessment, and to assess thyroid, immunological and glycemic function. Methods: a randomized and placebo controlled study for 2 years, followed by an open label follow-up of 2 years. We evaluated 59 elderly patients with mild cognitive impairment with accomplishment of at least two years of the controlled phase. Renal function was estimated by the aMDRD and CKD-EPI equation, and by laboratory and clinical data collected during the trial. The thyroid, immunological and glycemic functions were respectively evaluated by TSH, free T4, leukocyte count, neutrophil count, lymphocyte count, fasting plasma glucose and insulin, and the HOMA-IR. The clinical safety was evaluated through systematic examination performed every 3 months, with physical examination, clinical interview and UKU scale for adverse effects. Results: There was no decline of renal function with the use of lithium (litemia between 0.25-0.5 mmol/l) both in the aMDRD (p=0.453) and CKD-EPI (p=0.181) equations. A significant increase of neutrophils (p=0.038) and TSH (p=0.034) were observed. The lithium group showed significantly higher incidence of diabetes mellitus (p=0.037), arrhythmias (p=0.028), weight gain (p=0.015), more symptoms of UKU scale (p=0.045), and greater interference from the adverse effects of lithium during daily activities (p<0.001). There was an observed correlation between the opinion of the attending physician and the patient in respect to the interference in daily activities secondary to the adverse symptoms (p<0.001). Conclusions: The use of lithium in low doses did not result in renal function impairment, produced subtle changes in the immunological system and thyroid function, and was clinically safe for adverse effects. The reasons for the increased incidence of arrhythmias and diabetes mellitus deserve further investigation

La maladie d’Alzheimer (MA) est à l’origine de la majorité des cas de démence chez les personnes âgées. Son diagnostic précoce est essentiel pour mieux comprendre les mécanismes cérébraux sous-tendant la manifestation phénotypique de la maladie et développer des interventions conséquentes. Le fait d’étudier des individus à risque de développer la MA, par exemple ceux présentant un déclin cognitif subjectif (DCS) ou un trouble cognitif léger (TCL), offre l’opportunité d’examiner les processus neuropathophysiologiques qui précèdent le stade démentiel. Cela permettrait, entre autres, d’identifier des biomarqueurs avant-coureurs de la maladie. Cette thèse avait pour but d’investiguer la présence d’hyperactivation cérébrale chez des individus à risque de développer la MA, et d’examiner les réseaux cérébraux fonctionnels associés à l’hyperactivation. L’hyperactivation se définit par la présence de niveaux supérieurs d’activation cérébrale chez des personnes faisant partie de groupes à risque pour la MA (p.ex. DCS ou TCL), comparativement à des participants contrôles cognitivement sains. L’hyperactivation est le plus souvent mesurée par l’imagerie par résonance magnétique fonctionnelle (IRMf) en condition de réalisation de tâche. Dans cette thèse, le lecteur ou la lectrice sera d’abord exposée aux études ayant utilisé l’IRMf pour examiner les patrons d’activation cérébrale et de connectivité fonctionnelle chez les individus ayant reçu un diagnostic clinique de MA, de TCL ou présentant un DCS. Les modèles théoriques découlant de ces études seront ensuite présentés. Afin de mieux comprendre le phénomène d’hyperactivation et sa relation avec les patrons de connectivité fonctionnelle, les divers enjeux scientifiques qui demeurent à être abordés seront ensuite décrits (Chapitre 1). Trois articles exposant les études empiriques formant le corps de la thèse seront ensuite présentés. La première étude avait pour but de documenter la présence, la localisation et l’évolution longitudinale de l’hyperactivation iv associée à une tâche de mémoire épisodique chez des individus qui rencontrent les critères de TCL et qui ont ultérieurement progressé vers une démence (Chapitre 2). La deuxième étude visait à déterminer la trajectoire de l’activation cérébrale associée à une tâche de mémoire associative en fonction du degré de sévérité de la maladie chez un groupe d’individus à risque de développer la MA. Elle avait également pour but de déterminer la présence d’hyperactivation chez des personnes rencontrant les critères de DCS plus (ou DCS+), qui sont des individus présentant une plainte de mémoire ainsi que des marqueurs génétiques et/ou de neurodégénérescence pour la MA (Chapitre 3). La troisième étude avait pour but d’examiner les réseaux cérébraux fonctionnels associés aux régions montrant de l’hyperactivation chez des individus à risque de développer la MA. Elle avait également pour objectif d’évaluer comment l’hyperactivation et ces réseaux cérébraux fonctionnels sont reliés aux performances en mémoire (Chapitre 4). Les résultats découlant de l’étude 1 ont permis de mettre en évidence la présence d’hyperactivation chez des individus présentant un TCL et ayant ultérieurement progressé vers le stade de démence. Les trouvailles de l’étude 2 indiquent qu’une fonction quadratique décrit la relation entre des indices de sévérité de la maladie et l’activation pariétale supérieure gauche chez un groupe d’individus à risque de développer la MA (DCS+ et TCL). Par ailleurs, des niveaux supérieurs d’activation, c’est-à-dire de l’hyperactivation, étaient retrouvés dans les hippocampes + et plusieurs régions temporo-pariétales dans le groupe d’individus DCS . Une hypoactivation pariétale supérieure gauche était plutôt retrouvée chez les individus TCL. Enfin, les résultats de l’étude 3 indiquent que l’hyperactivation de régions prédéterminées est associée à la dysfonction de réseaux cérébraux fonctionnels impliqués dans les processus de mémoire associative dans le DCS+ et le TCL. De plus, ces interactions hyperactivation-réseaux étaient associées à une symptomatologie cognitive croissante. Les implications de cette thèse et ses limites sont abordées dans la discussion (Chapitre 5). / Alzheimer's disease (AD) is the most common cause of dementia in older adults. Its early diagnosis is essential to better understand the brain mechanisms underlying the phenotypical manifestation of the disease and develop consequent interventions. The study of individuals at risk of AD, for example those presenting with subjective cognitive decline (SCD) or mild cognitive impairment (MCI), offers the opportunity to examine the neuropathophysiological processes preceding the dementia stage. This would allow, among other things, to identify early biomarkers of the disease. The general aim of this thesis was to determine the presence of cerebral hyperactivation and to assess functional brain networks associated with hyperactivation. Hyperactivation is defined by the presence of higher levels of brain activation in individuals at risk of AD (i.e. SCD, MCI) in comparison to cognitively healthy controls. Hyperactivation is most often measured with functional magnetic resonance imaging (fMRI) while participants perform a cognitive task. In this thesis, the reader will first be exposed to the studies which used fMRI to examine patterns of brain activation and connectivity in individuals with a clinical diagnosis of AD, MCI or presenting with SCD. Theoretical models resulting from these studies will then be presented. The scientific issues remaining to be addressed to better understand the phenomenon of hyperactivation and its relation to functional brain networks will then be described (Chapter 1). Three empirical studies forming the core of this thesis will be presented. The first study aimed to assess the presence, localization and longitudinal evolution of hyperactivation associated with an episodic memory task in individuals meeting criteria for MCI and having subsequently progressed towards dementia (Chapter 2). The second study aimed to determine the trajectory of brain activation associated with an associative memory task as a function of disease severity in a group of individuals at risk of AD. It also aimed to determine if hyperactivation is present in viii participants meeting criteria for SCD plus (or SCD+), who are individuals presenting with memory complaint in addition to genetic and/or neurodegeneresence markers of AD (Chapter 3). The third and last study aimed to examine patterns of functional connectivity related to regions of hyperactivation, and to assess how hyperactivation and its associated functional networks relate to memory performance in individuals at risk of AD (Chapter 4). Results from the first study highlighted the presence of hyperactivation in individuals with MCI who subsequently progressed to the dementia stage. Findings from the second study revealed a quadratic function describing the relationship between proxies of disease severity (neurodegeneration, memory performance) and left superior parietal activation in a group of individuals at risk of AD (SCD+ and MCI). Moreover, higher levels of activation, i.e. hyperactivation, were found in hippocampal and temporo-parietal regions in the SCD+ group. Hypoactivation was rather found in the left superior parietal area in the MCI group. Finally, results from the third study revealed that hyperactivation of predetermined regions was associated with dysfunction of functional brain networks underlying associative memory in SCD+ and MCI. Moreover, these hyperactivation-network interactions were associated with increasing symptomatology. The implications of this thesis and its limits are addressed in the discussion section (Chapter 5).

[pt] O envelhecimento em todo o mundo é um dos maiores desafios da saúde. Nesse contexto, condições clínicas como demências e Comprometimento Cognitivo Leve (CCL) também aumentam suas prevalências. A causa de demência mais frequente e estudada é demência de Alzheimer (DA). Tradicionalmente, DA é caracterizada pelo déficit precoce na memória episódica. Entretanto, estudos atuais mostram que a DA apresenta heterogeneidade neuropsicológica e alguns pacientes apresentam déficits cognitivos precoces não-amnésticos. Essas apresentações são chamadas por alguns autores de DA atípica. Dessa forma, a primeira parte dessa tese dedicou-se a estudar a heterogeneidade neuropsicológica na DA através de dois estudos: uma revisão sistemática sobre heterogeneidade neuropsicológica na DA (publicado) e um estudo de casos sobre perfis típico e atípico na DA (publicado). A revisão sistemática tornou-se necessária já que foi a primeira revisão sistemática publicada sobre o tema. Os achados dos dois estudos mostraram que aspectos atípicos na DA precisam ser mais explorados, já que DA não é uma condição homogênea. Compreender esses perfis cognitivos na DA irá interferir nos métodos diagnósticos e intervenções terapêuticas, seja farmacológica ou comportamental. A segunda parte dessa tese explora esses aspectos atípicos em três amostras: envelhecimento normal, CCL e AD. Assim, um estudo transversal foi realizado para comparar medidas de velocidade de processamento (VP), controle inibitório e automonitoramento nas três amostras. Os resultados desse estudo mostram que medidas de VP podem ser indicadores precoces do declínio cognitivo envelhecimento. Ao comparar CCL com o grupo de envelhecimento saudável, os dados mostram diferença nas medidas de VP e erros cometidos nos testes de VP. Entretanto, as duas amostras não apresentaram diferenças nas medidas de funções executivas (FEs) e nas medidas de funcionalidade. CCL versus AD mostraram diferenças nas medidas de VP, funções executivas e funcionalidade. Dessa forma, esse estudo traz resultados relevantes para o diagnóstico precoce de CCL e novas diretrizes para o cenário clínico e pesquisa. Além disso, na segunda parte desta tese foi realizado um artigo sobre acurácia diagnóstica das medidas de VP nos casos de CCL e AD. A literatura mostra falta de estudos sobre diferenças nas medidas de VP no envelhecimento e parâmetros diagnósticos dos instrumentos de VP. Esse estudo mostrou que medidas de VP apresentam habilidades discriminativas, para DA e CCL. Esses dados são necessários, já que apresentamos um cenário de escassez de instrumentos com elevados parâmetros diagnósticos para medidas de VP no envelhecimento. Esse cenário torna-se ainda mais drástico, quando falamos de Brasil. / [en] Aging is a major healthcare challenge worldwide. With aging, the prevalence of conditions such as dementia and Mild Cognitive Impairment increase. The most frequent and studied cause of dementia is Alzheimer s dementia (AD). Traditionally, AD is characterized by early deficit in episodic memory. However, current studies show that AD presents heterogeneity in clinical manifestations, especially cognitive manifestations. Thus, some patients present a non-amnestic cognitive profile. These profiles are called by some authors as atypical AD. The first part of this thesis was aimed at studying the neuropsychological heterogeneity in AD by means of 2 studies: a systematic review on neuropsychological heterogeneity in AD (published) and cases of study with typical and atypical AD patients (published). The systematic review was necessary, as it was the first published review about the topic. The findings of the two studies show that atypical aspects in AD need to be further explored, since AD is not a homogeneous condition. Understanding these cognitive profiles in AD will interfere in diagnostic methods and therapeutic interventions, either pharmacological or behavioral ones. The second part of this thesis explores atypical aspects in three samples: normal aging, MCI and AD. Thus, a cross-sectional study was conducted to compare measures of processing speed (PS), inhibitory control, working memory and cognitive flexibility in the three samples. The results of this study showed that PS measures may be early indicators of cognition decline in aging. MCI versus normal aging showed differences in PS measures and errors in tests of PS. However, these samples did not show differences in executive function measures (EFs) and functional measures. Nevertheless, MCI versus AD show differences in PS measures, executive functions and functionality. Thus, this study showed relevant results for the diagnosis process of MCI and new guidelines for clinical settings and research. In addition, in the second part of this thesis an article was written on diagnostic accuracy of the PS measures used in cases of MCI and AD. The literature shows a lack of studies on differences in PS measures in aging and diagnostic parameters of PS instruments. This study showed that PS measures present discriminative abilities in AD and MCI. These data are important, as there is a lack of diagnostic tools for PS in aging, especially in the Brazilian scenario.

Yes / To determine whether jugular venous reflux (JVR) is associated with cerebral white matter changes (WMCs) in individuals with Alzheimer's disease (AD), we studied 12 AD patients 24 mild cognitive impairment (MCI) patients, and 17 elderly age- and gender-matched controls. Duplex ultrasonography and 1.5T MRI scanning was applied to quantify cerebral WMCs [T2 white matter (WM) lesion and dirty-appearing-white-matter (DAWM)]. Subjects with severe JVR had more frequently hypertension (p = 0.044), more severe WMC, including increased total (p = 0.047) and periventricular DAWM volumes (p = 0.008), and a trend for increased cerebrospinal fluid volumes (p = 0.067) compared with the other groups. A significantly decreased (65.8%) periventricular DAWM volume (p = 0.01) in the JVR-positive AD individuals compared with their JVR-negative counterparts was detected. There was a trend for increased periventricular and subcortical T2 WMC lesion volumes in the JVR-positive AD individuals compared with their JVR-negative counterparts (p = 0.073). This phenomenon was not observed in either the control or MCI groups. In multiple regression analysis, the increased periventricular WMC lesion volume and decreased DAWM volume resulted in 85.7% sensitivity and 80% specificity for distinguishing between JVR-positive and JVR-negative AD patients. These JVR-WMC association patterns were not seen in the control and MCI groups. Therefore, this pilot study suggests that there may be an association between JVR and WMCs in AD patients, implying that cerebral venous outflow impairment might play a role in the dynamics of WMCs formation in AD patients, particularly in the periventricular regions. Further longitudinal studies are needed to confirm and validate our findings.