Orientador: Flávia Roberta Faganello Navega / Banca: Rodrigo Vitorio / Banca: Karina Gramani Say / Resumo: Introdução: Vibração de Corpo Todo (VCT) é uma das ferramentas que a cada dia tem sido mais utilizada na reabilitação de diferentes populações. Alguns estudos atribuem uma melhora no desempenho muscular devido à aplicação da vibração resultando em benefícios para aspectos motores relacionados com a mobilidade funcional. Pessoas com Doença de Parkinson apresentam alguns sinais clínicos, dentre eles a rigidez muscular. Essa característica pode comprometer a marcha desses indivíduos. Objetivo: Analisar a influência do treinamento agudo com VCT durante a marcha habitual e com desvio de obstáculo em indivíduos sem acometimentos neurológicos e indivíduos com Doença de Parkinson. Métodos: Participaram do estudo pessoas com o diagnóstico médico de Doença de Parkinson e indivíduos da comunidade sem doenças neurológicas, os quais foram divididos em quatro grupos: grupo Parkinson (GP, n=9), grupo Parkinson placebo (GPP, n=9), grupo controle (GC, n=9) e grupo controle placebo (GCP, n=9). A coleta de dados foi realizada em um único dia. Os dados pessoais, medidas antropométricas, MEEM, os parâmetros espaço-temporais e co-contração muscular (tibial anterior/gastrocnêmio medial e tibial anterior/gastrocnêmio lateral) durante a marcha foram coletados antes do protocolo com a plataforma vibratória. Após os 30 minutos de treinamento com vibração (f= 30 Hz), foi realizada, novamente, a avaliação da marcha. As variáveis espaço-temporais consideradas para análise foram o comprimento, largura, dur... (Resumo completo, clicar acesso eletrônico abaixo) / Abstract: Introduction: Whole Body Vibration (VCT) is one of the tools that has been increasingly used every day for the rehabilitation and treatment of different populations. Some studies attribute an improvement at muscular performance due to the application of vibrations, through the easiness of the reflection, resulting in benefits for the motors related to functional mobility. People with Parkinson's disease show some clinical signs like muscle rigidity. This feature may impair their gait. Objective: Analyze the acute effect of WBV in individuals without neurological impairments and people with Parkinson's Disease during usual gait and obstacle circumvention. Methods: People diagnosed with Parkinson's disease and individuals of community without neurological impairments participated in the study. They were divided into four groups: Parkinson's group (GP, n=9), Parkinson's placebo group (GPP, n=9), control group (GC, n=9) and control placebo group (GCP, n=9). Data collection was done in a single day. Personal data, anthropometric measures, MEEM, spatiotemporal gait parameters and muscle co-contraction (tibialis anterior/gastrocnemius medialis and tibialis anterior/gastrocnemius lateralis) analysis during gait were collected before the protocol with a vibrating platform. After the 30 minutes of vibration training (f= 30 Hz), evaluation of gait were performed again. The spatiotemporal variables considered for analysis were the length, width, duration and speed of the step and percent... (Complete abstract click electronic access below) / Mestre

Considerada universal, a doença de Parkinson (DP) ocupa a segunda posição entre as doenças neurodegenerativas mais comuns em idosos. A depressão é a comorbidade psiquiátrica mais comumente associada à esta doença e tem sido apontada repetidamente como a principal determinante da piora da qualidade de vida (QV) nestes pacientes como também um dos fatores que levam à pior adesão aos medicamentos propostos. Neste contexto o objetivo do presente estudo foi avaliar a prevalência de depressão em pacientes com DP em seguimento em um ambulatório especializado como também verificar o impacto da depressão na QV destes pacientes e na adesão ao tratamento com levodopa. O estudo foi realizado no ambulatório de distúrbios do movimento do Hospital das Clínicas da Faculdade de Medicina de Ribeirão Preto - USP. Foram selecionados 112 pacientes consecutivos com diagnóstico de DP em uso de levodopa, que foram entrevistados por meio da aplicação das seguintes escalas: Escala geriátrica de depressão com 15 itens (GDS-15), Parkinson\'s disease questionnaire-39 item version (PDQ-39), teste Morisky e Green e o Instrumento para Avaliar Atitudes Frente à Tomada de Remédios (IAAFTR). Foi encontrada a prevalência de depressão de 25% (n=28) entre os pacientes e uma forte correlação entre a GDS-15 e todas as dimensões do PDQ-39, evidenciando o real impacto que a depressão causa na QV dos pacientes com DP. Dos 112 pacientes, 53% (n=59) não apresentaram adesão ao seu tratamento, sendo que 52% reportaram que são descuidados quanto ao horário de tomarem sua medicação. Não foi encontrada correlação entre a presença de sintomas depressivos e a adesão do paciente à sua terapia antiparkinsoniana. O estudo demonstrou que a depressão está associada à piora da QV em pacientes com DP, afetando todas suas dimensões, especialmente a dimensão mobilidade. Toda a equipe de saúde que cuida destes pacientes devem ser encorajados e preparados para ajudar na investigação de sintomas depressivos na DP, por ser o seu tratamento a base crucial para a melhora da QV destes pacientes. / Considered as universal, Parkinson\'s disease (PD) ranks second among the most common neurodegenerative diseases in the elderly. Depression is the most common psychiatric comorbidity associated with this disease and has been identified repeatedly as the main determinant of the worsening of quality of life (QoL) in these patients but also one of the factors that lead to poor adherence to medication proposed. In this context, the objective of this study was to evaluate the prevalence of depression in PD patients followed up in a specialized clinic and also to verify the impact of depression on the QoL of these patients and adherence to treatment with levodopa. The study was conducted in movement disorders clinic of the Hospital das Clinicas, Faculty of Medicine of Ribeirão Preto - USP. We selected 112 consecutive patients diagnosed with PD in use of levodopa, who were interviewed by the application of the following scales: Geriatric Depression Scale with 15 items (GDS-15), Parkinson\'s disease questionnaire-39 item version (PDQ-39), Morisky and Green test and Instrument to Measure Attitudes Toward Taking Medications (IAAFTR). A prevalence of depression of 25% (n = 28) and a strong correlation was found between the GDS-15 and all dimensions of the PDQ-39, showing the real impact that depression causes the QoL of patients with PD. Of the 112 patients, 53% (n = 59) showed no adherence to their treatment, and 52% reported that they are careless as to the time to take your medication. No correlation was found between presence of depressive symptoms and patient adherence to their therapy. The study showed that depression is associated with decreased quality of life in patients with PD, affecting all its dimensions, especially the mobility dimension. Health team that takes care of these patients should be encouraged and prepared to assist in the investigation of depressive symptoms in PD, its treatment to be the crucial basis for the improvement of QoL of these patients

Considerada universal, a doença de Parkinson (DP) ocupa a segunda posição entre as doenças neurodegenerativas mais comuns em idosos. A depressão é a comorbidade psiquiátrica mais comumente associada à esta doença e tem sido apontada repetidamente como a principal determinante da piora da qualidade de vida (QV) nestes pacientes como também um dos fatores que levam à pior adesão aos medicamentos propostos. Neste contexto o objetivo do presente estudo foi avaliar a prevalência de depressão em pacientes com DP em seguimento em um ambulatório especializado como também verificar o impacto da depressão na QV destes pacientes e na adesão ao tratamento com levodopa. O estudo foi realizado no ambulatório de distúrbios do movimento do Hospital das Clínicas da Faculdade de Medicina de Ribeirão Preto - USP. Foram selecionados 112 pacientes consecutivos com diagnóstico de DP em uso de levodopa, que foram entrevistados por meio da aplicação das seguintes escalas: Escala geriátrica de depressão com 15 itens (GDS-15), Parkinson\'s disease questionnaire-39 item version (PDQ-39), teste Morisky e Green e o Instrumento para Avaliar Atitudes Frente à Tomada de Remédios (IAAFTR). Foi encontrada a prevalência de depressão de 25% (n=28) entre os pacientes e uma forte correlação entre a GDS-15 e todas as dimensões do PDQ-39, evidenciando o real impacto que a depressão causa na QV dos pacientes com DP. Dos 112 pacientes, 53% (n=59) não apresentaram adesão ao seu tratamento, sendo que 52% reportaram que são descuidados quanto ao horário de tomarem sua medicação. Não foi encontrada correlação entre a presença de sintomas depressivos e a adesão do paciente à sua terapia antiparkinsoniana. O estudo demonstrou que a depressão está associada à piora da QV em pacientes com DP, afetando todas suas dimensões, especialmente a dimensão mobilidade. Toda a equipe de saúde que cuida destes pacientes devem ser encorajados e preparados para ajudar na investigação de sintomas depressivos na DP, por ser o seu tratamento a base crucial para a melhora da QV destes pacientes. / Considered as universal, Parkinson\'s disease (PD) ranks second among the most common neurodegenerative diseases in the elderly. Depression is the most common psychiatric comorbidity associated with this disease and has been identified repeatedly as the main determinant of the worsening of quality of life (QoL) in these patients but also one of the factors that lead to poor adherence to medication proposed. In this context, the objective of this study was to evaluate the prevalence of depression in PD patients followed up in a specialized clinic and also to verify the impact of depression on the QoL of these patients and adherence to treatment with levodopa. The study was conducted in movement disorders clinic of the Hospital das Clinicas, Faculty of Medicine of Ribeirão Preto - USP. We selected 112 consecutive patients diagnosed with PD in use of levodopa, who were interviewed by the application of the following scales: Geriatric Depression Scale with 15 items (GDS-15), Parkinson\'s disease questionnaire-39 item version (PDQ-39), Morisky and Green test and Instrument to Measure Attitudes Toward Taking Medications (IAAFTR). A prevalence of depression of 25% (n = 28) and a strong correlation was found between the GDS-15 and all dimensions of the PDQ-39, showing the real impact that depression causes the QoL of patients with PD. Of the 112 patients, 53% (n = 59) showed no adherence to their treatment, and 52% reported that they are careless as to the time to take your medication. No correlation was found between presence of depressive symptoms and patient adherence to their therapy. The study showed that depression is associated with decreased quality of life in patients with PD, affecting all its dimensions, especially the mobility dimension. Health team that takes care of these patients should be encouraged and prepared to assist in the investigation of depressive symptoms in PD, its treatment to be the crucial basis for the improvement of QoL of these patients

The aim of this work is to evaluate the fuzzy system for different types of patients for levodopa infusion in Parkinson Disease based on simulation experiments using the pharmacokinetic-pharmacodynamic model. Fuzzy system is to control patient’s condition by adjusting the value of flow rate, and it must be effective on three types of patients, there are three different types of patients, including sensitive, typical and tolerant patient; the sensitive patients are very sensitive to drug dosage, but the tolerant patients are resistant to drug dose, so it is important for controller to deal with dose increment and decrement to adapt different types of patients, such as sensitive and tolerant patients. Using the fuzzy system, three different types of patients can get useful control for simulating medication treatment, and controller will get good effect for patients, when the initial flow rate of infusion is in the small range of the approximate optimal value for the current patient’ type.

In this thesis, the learning of probabilistic relationships between stimulus-action pairs is investigated under the probability learning paradigm. The effect of reward is investigated in the first three experiments. Additionally, the effect of context and uncertainty is investigated in the second and third experiments, respectively. The fourth experiment is the replication of the second experiment with a group of Parkinson patients where the effect of dopamine medication on probability learning is studied. In Experiment 1, we replicate the classical probability learning task by comparing monetary and non-monetary reward feedback. Probability learning behavior is observed in both monetary and non-monetary rewarding feedback conditions. However, no significant difference between the monetary and non-monetary feedback conditions is observed. In Experiment 2, a variation of the probability learning task which includes irrelevant contextual information is applied. Probability learning behavior is observed, and a significant effect is found between monetary and non-monetary feedback conditions. In Experiment 3 / a probability learning task similar to that in Experiment 2 is applied, however, in this experiment, stimulus included relevant contextual information. As expected, due to the utilization of the relevant contextual information from the start of the experiment, no significant effect is found for probability learning behavior. The effect of uncertainty observed in this experiment is a replication of the reports in literature. Experiment 4 is identical to Experiment 2 / except that the subject population is a group of dopamine medicated Parkinson patients and a group of age matched controls. This experiment is introduced to test the suggestions in the literature regarding the enhancement effect of dopamine medication in probability learning based on positive feedback conditions. In Experiment 4, probability learning behavior is observed in both groups, but the difference in learning performance between Parkinson patients and controls was not significant, probably due to the low number of subject recruited in the experiment. In addition to these investigations, learning mechanisms are also examined in Experiments 1 and 4. Our results indicate that subjects initially search for patterns which lead to probability learning. At the end of Experiments 1 and 4, upon learning the winning frequencies, subjects change their behavior and demonstrate maximization behavior, which makes them prefer continuously one option over the other.

Diss. (sammanfattning) Göteborg : Göteborgs universitet, 2009. / Härtill 5 uppsatser.

Diss. (sammanfattning) Stockholm : Karolinska institutet, 2009. / Härtill 4 uppsatser.

Στην παρούσα εργασία μελετήθηκαν 15 ασθενείς με νόσο Parkinson (8 γυναίκες, 7 άνδρες, μέσος όρος ηλικίας τα 62χρόνια, μέση διάρκεια της νόσου από τη διάγνωση τα 11 χρόνια), σε διάφορα στάδια της νόσου (τέσσερις ασθενείς σταδίου 2, δύο ασθενείς σταδίου 2.5, 2 ασθενείς σταδίου 3, πέντε ασθενείς σταδίου 4, ένας σταδίου 4.5 και ένας ασθενής σταδίου 5 κατά Hoehn & Yahr ). Και στους 15 ασθενείς πραγματοποιήθηκε διπλός απεικονιστικός έλεγχος με τομογραφία εκπομπής μονήρους φωτονίου (SPECT). Στην πρώτη SPECT απεικόνιση μελετούμε τον βαθμό της ακεραιότητας της μελανοραβδωτής οδού, με τη χρήση ειδικού ραδιοφαρμάκου που προσδένεται εκλεκτικά στον μεταφορέα της ντοπαμίνης (DA Transporter – DAT). Στη δεύτερη SPECT απεικόνιση μελετούμε την αιματική εγκεφαλική ροή των ασθενών σε συνθήκες ηρεμίας, η οποία αντικατοπτρίζει και το βαθμό μεταβολικής ενεργότητας της κάθε περιοχής του εγκεφάλου. Για την αντικειμενική εκτίμηση της μελέτης αιμάτωσης πραγματοποιήθηκε στατιστική παραμετρική σύγκριση με βάση δεδομένων φυσιολογικών ατόμων της ίδιας ηλικίας. Σκοπός μας ήταν να δούμε ποιες περιοχές του εγκεφάλου υποαιματώνονται και συνεπώς επηρεάζονται, στη νόσο του Parkinson. Πράγματι είδαμε ότι η διαταραχή που προκαλείται στο κύκλωμα των βασικών γαγγλίων από την έλλειψη της ντοπαμίνης (DA), προκαλεί διαταραχές στη φλοιοραβδωτή οδό κάτι που αντικατοπτρίζεται στην υποαμάτωση κυρίως του μετωπιαίου λοβού και ειδικότερα της προκινητικής και συμπληρωματικής περιοχής και των συνειρμικών περιοχών του μετωπιαίου λοβού. Επίσης στα πιο προχωρημένα στάδια της νόσου, παρατηρήθηκε στατιστικά σημαντική υποαιμάτωση και σε περιοχές του βρεγματικού και κροταφικού λοβού. Τα ευρήματα αυτά είναι πολύ σημαντικά και μας βοηθούν να κατανοήσουμε καλύτερα τα κινητικά και μη-κινητικά συμπτώματα (διαταραχές της νόησης) στη συγκεκριμένη νόσο. / In the present study we examined 15 Parkinson disease patients (8 females, 7 males, mean age = 62years, mean duration of the disease from diagnosis = 11years) in various stages (according to Hoehn & Yahr staging system) of the disease (stage2: 4 pts, stage2.5: 2 pts, stage3: 2pts, stage 4: 5pts, stage 4.5:1pt, stage 5: 1 pt). Each patient underwent two different SPECT studies. First was performed a SPECT study with the radiopharmaceutical DaTSCAN, that is specifically bind to the Dopamine Transporter (DAT), a protein on the presynaptic dopaminergic nerve terminal. In that way we can image and also quantify the degeneration of the nigrostriatal pathway, that is afflicted in PD. Secondly we performed a brain perfusion SPECT study with the radiopharmaceutical ECD, in order to find out if there were regions of hypoperfusion in the cerebral cortex of the patients. We used an objective and dependable statistical program that enables the comparison of each perfusion study with an age-matched data base o normal perfusions. We found in all 15 patients statistically significant differences in areas of Frontal lobes and especially in the PRE-SMA (pre-motor and supplementary motor cortex) and association areas of frontal cortex. In progressive stages of the disease there were also other areas of the cerebral cortex hypoperfused (parietal and temporal lobes). These findings seem to be very useful for better understanding motor and non-motor (cognitive and affective) symptoms in PD.

No description available.

The molecular mechanisms underlying the association between mutations in GBA1 and risk of developing the ‘synucleinopathy’ disorders Parkinson’s disease (PD) and dementia with Lewy bodies (DLB) remain elusive. To better understand the precise molecular cascade that connects GBA1 mutations with α-synuclein dysregulation, a modified lipid extraction and HPTLC protocol was optimized to detect changes in levels of neutral sphingolipids (SLs) from neural cells and tissue expressing wild-type (WT) GBA1, mutant GBA1, or both. We demonstrate that mutant GBA1 does not confer a dominant-negative effect on WT GBA1-mediated activity; however, bona fide loss-of-enzymatic function mutation events led to the accumulation of lipid substrates in neural cells and tissue, and enhance α- synuclein/ubiquitin reactivity in brain tissue of mutant gba1 mice. Our HPLC-MS/MS data are consistent with other studies demonstrating that heterozygous GBA1 mutations do not lead to lipid accumulation, but may alter α-synuclein degradation through a yet-to-be defined novel gain-of-toxic function event.