- / -

Made available in DSpace on 2015-07-22T20:49:20Z (GMT). No. of bitstreams: 0 Previous issue date: 2011-01-26 / Avaliar a freqüência de ocorrência e caracterizar a tipologia das disfluências em indivíduos com DP, correlacionando-as com a disartria e as alterações práxicas verbais e não-verbais. Métodos: foi realizado um estudo transversal com amostra composta por 60 adultos pareados por sexo, idade e escolaridade. O grupo I foi formado por 30 adultos com DP idiopática, freqüentadores do setor de Distúrbios do Movimento da Disciplina de Neurologia da Universidade Federal de São Paulo e o grupo II por 30 adultos sadios. Para a avaliação da fluência da fala foi solicitada a emissão de uma narrativa a partir de uma seqüência de figuras que formam “A estória do cachorro” e realizada a trascrição de 200 sílabas fluentes para verificação das disfluências e da velocidade de fala. Para a avaliação dos aspectos motores da fala foi utilizado o protocolo de disartria e para a avaliação da praxia de fala, foi utilizada a tarefa de agilidade oral do teste de Boston para o Diagnóstico da Afasia. O desempenho dos sujeitos com DP foi comparado ao do grupo controle. Resultados: não houve diferença entre os grupos estudados com relação ao sexo, idade e escolaridade. O GDP apresentou maior número de disfluências atípicas e totais na fala e pior desempenho práxico verbal e não-verbal comparado ao GC. Todos sujeitos do DP apresentaram disartria hipocinética. As disfluências típicas e as típicas da fala foram relacionadas mais fortemente ao quadro de disartria do que o quadro de praxia verbal e não-verbal. Conclusão: as disfluências atípicas estão presentes na fala de pacientes com DP, estando mais relacionadas à disartria. / Purpose: to characterize the frequency of occurrence and typology of disfluencies in individuals with PD verifying their relationship with the dysarthria and praxis verbal and nonverbal. Methods: This was a transversal observational study in which were analyzed 60 subjects, over 60 years, paired by their age and gender. The group was composed by 30 normal controls patients and 30 with PD. In order to evaluate the speech fluency, it was requested to the patients to narrate a story based on a picture description with seven pictures and was realized a transcript of 200 fluent syllables for verification of disfluencies and speech rate. So it was able to evaluate the speech praxis by the Boston Diagnosis of Aphasia, a dysarthria protocol. The patient’s performance was compared with the control group. Results: there was no difference between groups regarding gender, age and education. The PDG presented a greater number of total and atypical disfluencies in speech and worst praxis verbal and nonverbal compared to CG. All subjects with PD presented hypokinetic dysarthria. Typical and atypical disfluencies of speech were highly related to the dysarthria frame than to the praxis verbal and non-verbal ones. Conclusion: the atypical disfluencies are present in the speech of PD patients and they are more related to the dysarthria. / TEDE

Submitted by Fabio Sobreira Campos da Costa (fabio.sobreira@ufpe.br) on 2016-07-22T14:26:02Z No. of bitstreams: 2 license_rdf: 1232 bytes, checksum: 66e71c371cc565284e70f40736c94386 (MD5) Dissertação de Mestrado - Dharah Puck.pdf: 1776435 bytes, checksum: 27ab98da9413ed5fb8c5069b41cffabc (MD5) / Made available in DSpace on 2016-07-22T14:26:03Z (GMT). No. of bitstreams: 2 license_rdf: 1232 bytes, checksum: 66e71c371cc565284e70f40736c94386 (MD5) Dissertação de Mestrado - Dharah Puck.pdf: 1776435 bytes, checksum: 27ab98da9413ed5fb8c5069b41cffabc (MD5) Previous issue date: 2016-02-17 / Este estudo teve como objetivo compreender a percepção do cuidador familiar acerca do cuidar do idoso acometido pela doença de Parkinson (DP). Trata-se de um estudo descritivo, com abordagem qualitativa, o qual foi realizado no Programa de Extensão Pró-Parkinson da Universidade Federal de Pernambuco, junto aos cuidadores familiares dos idosos atendidos nesse serviço. Participaram 20 cuidadores que foram divididos em dois grupos (n=10) que cuidavam de parkinsonianos: no estágio HY1-HY2 (doença leve), e no estágio HY3-HY4 (doença moderada-grave). Utilizou-se um questionário semiestruturado com 15 questões subjetivas pertinentes aos problemas em estudo. Esse estudo, seguiu as determinações da Resolução de nº 466/2012 para pesquisas com seres humanos, aprovado pelo Comitê de Ética e Pesquisa da Universidade Federal de Pernambuco, sob o CAAE: 46834815.2.0000.5208. Os dados coletados foram submetidos à Análise de Conteúdo e Análise Léxica, na qual utilizou-se o software IRAMUTEQ. Após a análise conteúdo emergiram sete categorias temáticas relacionadas à percepção do cuidador familiar acerca do processo de cuidar do idoso com Parkinson: (1) Perfil sociodemográfico dos cuidadores familiares de idosos com Parkinson; (2) Perfil sociodemográfico e clínico dos idosos com Parkinson; (3) A construção do cuidar; (4) A informação como promotora da qualidade no cuidado; (5) As transformações em decorrência do cuidar; (6) Sentimentos e percepções do cuidador familiar; e (7) Finitude: como lidar com o processo morte/morrer na velhice. Com relação à Análise Léxica foi elaborado uma categoria principal: As significações e correlações do cuidar do idoso com Parkinson, que foi subdividida em três, sendo estas: (1) Plano fatorial das palavras mais significativas sobre o cuidar do idoso com Parkinson; (2) Árvore máxima de similitude; e (3) Nuvem representativa da Análise Lexical. Verificou-se que o vínculo familiar faz com que o cuidar seja mais intenso, o que pode acarretar em sobrecarga e um mister de sentimentos e percepções oriundos dessa atividade. Assim, é preciso pensar no bem-estar biopsicossocial do cuidador, valorizando seu papel e participação no processo de cuidar, contribuindo para que este busque e tenha acesso à informações de qualidade, com o intuito do constantemente aprimoramento da sua prática, tornando-a cada dia, mais segura e eficaz. / This study aimed to understand the perception of family caregivers about caring for the elderly affected by Parkinson's disease (PD). This is a descriptive study with a qualitative approach, which was held at the Pro-Parkinson Outreach Program of the Federal University of Pernambuco, near the family caregivers of the elderly seen in this service. Participated in 20 caregivers who were divided into two groups (n = 10) who took care of parkinsonian: in HY1-HY2 stage (mild disease), and HY3-HY4 stage (moderate-severe disease). We used a semi-structured questionnaire with 15 pertinent subjective questions to the problems under study. This study followed the provisions of Resolution nº 466/2012 of for human research, approved by the Research Ethics Committee of the Federal University of Pernambuco, under the CAAE: 46834815.2.0000.5208. The data collected were subjected to content analysis and Lexical analysis, which used the IRAMUTEQ software. After analyzing content emerged seven thematic categories related to the perception of caregivers about the process of caring for the elderly with Parkinson: (1) Socio-demographic profile of family caregivers of older adults with Parkinson; (2) socio-demographic and clinical profile of older people with Parkinson; (3) The construction of care; (4) Information as promoter of quality in care; (5) changes as a result of caring; (6) feelings and perceptions of family caregivers; and (7) Finitude: how to handle the process death / dying in old age. Regarding Lexical analysis has been prepared a main category: The significance and correlations of caring for the elderly with Parkinson's, which was subdivided into three, which are: (1) factorial plan of the most significant words, caring for the elderly with Parkinson; (2) Maximum Tree of similarity; and (3) representative Cloud Lexical Analysis. It was found that the family bond makes the care is more intense, which can lead to overload and mister feelings and perceptions resulting from this activity. So, we need to think about the well-being biopsychosocial caregiver, valuing their role and participation in the care process, contributing to this search and have access to quality information, always with the aim of improving their practice, making every day, safer and more effective.

Orientador: Gil Lucio Almeida / Dissertação (mestrado) - Universidade Estadual de Campinas, Instituto de Biologia / Made available in DSpace on 2018-08-05T03:20:59Z (GMT). No. of bitstreams: 1 Paulino_RodrigoGaiga_M.pdf: 1725272 bytes, checksum: bad6329e7b6f8807cc8798a0689dc64a (MD5) Previous issue date: 2005 / Resumo: Este estudo se propôs a analisar as características cinemáticas e eletromiográficas (EMG) dos movimentos voluntários uni-articulares unidirecionais e com reversão do cotovelo, em indivíduos jovens e idosos saudáveis, como também em indivíduos portadores da doença de Parkinson. Método: Os sujeitos permaneceram sentados em uma cadeira, com o antebraço direito sobre um ¿manipulandum¿ horizontal, de modo que o cotovelo direito se posicionava sobre o eixo de rotação do ¿manipulandum¿. O ombro ficou abduzido a 90°, ou seja, com o braço na horizontal. Nos movimentos unidirecionais, os sujeitos eram instruídos a mover em direção a um alvo e parar (somente flexão), já nos movimentos com reversão foi necessário realizar os movimentos em direção ao alvo e depois reverte-lo a uma nova posição (flexão e extensão). Os movimentos foram realizados em amplitudes variadas, tanto de ida, quanto de retorno do movimento. Registrou-se a atividade EMG do músculo bíceps braquial (BIC) e do tríceps cabeça lateral (TR). Os portadores da doença de Parkinson foram avaliados em dois momentos, no período em que a medicação estava em sua ação mínima (cerca de 12 horas após a ultima dose da medicação) e reavaliados 1-1,5h após a ingestão do medicamento anti-parkinsoniano. Resultados: Em indivíduos jovens e idosos saudáveis observou-se que na fase de desaceleração ao alvo ocorre a supressão da atividade do segundo burst agonista (BIC) em movimentos com reversão. Nesta mesma fase houve um aumento da magnitude da atividade EMG do antagonista (TR) com a distância de retorno. Após a reversão, a atividade EMG do TR, que nesta fase atua como agonista, continua a modular a magnitude EMG com o aumento da distância de retorno. Os portadores da doença de Parkinson moveram mais lentamente que os indivíduos idosos saudáveis, diminuindo a magnitude dos bursts EMG durante a aceleração nos movimentos de ida e nos de retorno. No momento da desaceleração os parkinsonianos apresentaram um aumento na co-ativação entre o agonista e o antagonista. Após a medicação, os parkinsonianos moveram mais rapidamente e mostraram um aumento na magnitude da atividade EMG na fase de aceleração dos movimentos. Discussão: Os resultados demonstraram que o envelhecimento não modifica a modulação dos padrões de ativação EMG. A supressão do segundo burst agonista (BIC) otimiza a função do antagonista (TR) que atua desacelerando o membro. Na fase subsequente o TR acelera o membro em direção à posição inicial. O aumento da magnitude da atividade EMG do TR com a distância de retorno sugere que o sistema nervoso central gera a atividade EMG capaz de não apenas desacelerar o membro ao alvo, mas também reverter sua direção e lançá-lo de volta à posição inicial. Os portadores da doença de Parkinson apresentaram múltiplos bursts de aceleração de pequena magnitude, que levam o parkinsoniano a mover lentamente. A co-ativação entre o agonista e o antagonista no momento da desaceleração do movimento aumentou a estabilidade para que o movimento fosse revertido com mais precisão. Por fim, o uso da medicação anti-parkinsoniana sugere a melhora do planejamento motor durante os movimentos com reversão, aumentando a magnitude da atividade EMG durante os momentos de aceleração do movimento / Abstract: This study analyses the kinematic and electromyographic (EMG) patterns of the singlejoint unidirectional movement and with elbow reversion in young individuals, healthy elderly and also individuals with Parkinson's disease. Method: The individuals remained seated in a chair with the right forearm on a horizontal ¿manipulandum¿, so that the right elbow was placed on the ¿manipulandum¿ rotation axis. The shoulder was abducted at a 90° angle, which means, with the arm in the horizontal position. In the unidirectional movements, the individuals have been instructed to move towards a given target and stop (flexion only), whereas in the movements with reversion was necessary to perform movements towards the target and after reverse them to a new position (flexion and extension). The movements were performed in several amplitudes either forward or backward movements. Biceps biceps muscle (BIC) and also lateral head triceps (TR) EMG activities have been registered. The individuals with Parkinson's disease were evaluated in two moments, during the period when the medication was at its minimum action (about 12 hours after the last dose of the medication) and reevaluated after 1-1,5h after the ingestion of the antiparkinsonian medication. Results: It has been observed through the data obtained from young individuals and healthy elderly that a suppression of the activity of the second agonist burst (BIC) occurred during the target deceleration phase in reversion movements. In this same phase there was an increase of magnitude of the activity EMG of the antagonist (TR) with the return distance. After the reversion, the EMG activity of the TR, which in this phase acts as agonist, continues to modulate the magnitude with the increase of the return distance. The individuals with Parkinson's disease moved more slowly than the healthy elderly, decreasing the magnitude of the bursts EMG during the acceleration in forward and backward movements. In the moment of the deceleration the pakinsonians presented an increase in the co-activation between the agonist and the antagonist. After the medication was taken, the parkinsonians were able to move faster and showed an increase in the magnitude of the EMG activity during the acceleration phase of the movements. Discussion: The results have demonstrated that the aging process does not modify the modulations of the EMG activation patterns. The suppression of the second agonist burst (BIC) optimizes the antagonist (TR) function, which acts by decelerating the member. During the following phase, the TR accelerates the member towards the initial position. The increase of the magnitude of the EMG activity of the TR with the return distance suggests that the central nervous system generates the EMG activity which is capable of not only decelerating the limb to the target, but also of reversing its direction and cast it back to the initial position. The Parkinson disease subjects presented multiples bursts of short magnitude in acceleration phase, which make the parkinsonian move slowly. The co-activation between the agonist and the antagonist during the movement deceleration moment increased the stability so that the movement could be more precisely reverted. Finally, the anti-parkinsonian suggests the improvement of the motor planning during the movements with reversion, increasing the magnitude of the EMG activity during the moments of acceleration of the movement / Mestrado / Fisiologia / Mestre em Biologia Funcional e Molecular

Conselho Nacional de Desenvolvimento CientÃfico e TecnolÃgico / A doenÃa de Parkinson (DP) à uma desordem neurodegenerativa, caracterizada pela destruiÃÃo dos neurÃnios nigroestriatais dopaminÃrgicos. O tratamento atual para esta doenÃa està restrito ao alÃvio sintomÃtico, porque atà o presente momento nÃo existem agentes capazes de inibir a degeneraÃÃo neuronal. Existem evidÃncias experimentais de que antagonistas de receptores A2A da adenosina poderiam ser Ãteis no tratamento de DP. Com a finalidade de investigar essa possibilidade, o presente trabalho demonstrou os efeitos da cafeÃna e do CSC (8-(3-chlorostyryl caffeine) no comportamento rotacional e nas alteraÃÃes neuroquÃmicas em ratos lesionados com 6-OHDA, como modelo da doenÃa de Parkinson. Os animais (ratos Wistar machos, 250-280g) foram tratados com cafeÃna (10 e 20 mg/kg, i.p.) diariamente durante 14 dias, iniciando 1h apÃs a lesÃo ou 7 dias, iniciando seis dias apÃs a lesÃo com 6-OHDA ou com CSC (1 e 5 mg/kg, i.p.) diariamente durante 7 dias, iniciando 6 dias apÃs a lesÃo com 6-OHDA, sozinho ou associado com L-DOPA (CSC 1 mg/kg, i.p. + L-DOPA 50mg/kg + Benzerazida 12,5 mg/kg, i.p.). Os resultados mostraram que houve um aumento significativo do nÃmero de rotaÃÃes induzidas por apomorfina nos animais lesionados com 6-OHDA (50 vezes) quando comparados aos animais falso operados. O tratamento com cafeÃna, principalmente durante 14 dias e o tratamento com CSC produziram uma recuperaÃÃo motora parcial com reduÃÃo do nÃmero de rotaÃÃes. A 6-OHDA provocou morte neuronal evidenciada pela reduÃÃo dos nÃveis de monoaminas (75-85%) quando comparadas ao lado contralateral. Nos grupos tratados com cafeÃna ou CSC sozinho ou associado com L-DOPA a reduÃÃo dos nÃveis de DA, 5HT e seus metabÃlitos foi menor. As concentraÃÃes dos aminoÃcidos glutamato e GABA foram significativamente aumentadas (3,8 e 3 vezes, respectivamente) no estriado de ratos lesionados. O CSC reverteu essas alteraÃÃes significativamente e foi observada uma potencializaÃÃo desses efeitos na associaÃÃo com L-DOPA. Os experimentos in vitro demonstraram que a cafeÃna e o CSC apresentaram um forte efeito neuroprotetor nas cÃlulas mesencefÃlicas de rato expostas a 6-OHDA. O tratamento com CSC ou cafeÃna aumentou significativamente o nÃmero de cÃlulas viÃveis apÃs a exposiÃÃo das cÃlulas a 6-OHDA, como foi demonstrado pelo teste do MTT. A exposiÃÃo das cÃlulas mesencefÃlicas a 6-OHDA aumentou os conteÃdos de nitrito e a peroxidaÃÃo lipÃdica, que retornaram a concentraÃÃes normais apÃs tratamento com CSC ou cafeÃna. AlÃm disso, a 6-OHDA reduziu o nÃmero de cÃlulas normais e aumentou o nÃmero de cÃlulas apoptÃticas e o tratamento com CSC ou cafeÃna reverteu esses efeitos da 6-OHDA, promovendo aumento do nÃmero de cÃlulas viÃveis e reduÃÃo do nÃmero de cÃlulas apoptÃticas. Houve uma reduÃÃo do nÃmero de microglias ativadas apÃs a exposiÃÃo das cÃlulas a cafeÃna e a 6-OHDA, o mesmo nÃo ocorreu apÃs a exposiÃÃo das cÃlulas ao CSC e a 6-OHDA. O tratamento com cafeÃna reduziu o aumento do nÃmero de astrÃcitos reativos induzidos pela 6-OHDA, enquanto o CSC nÃo apresentou esse efeito. Esses resultados mostraram que ambos, a cafeÃna e o CSC apresentaram aÃÃes neuroprotetoras em cÃlulas mesencefÃlicas de rato expostas a 6-OHDA. O presente trabalho mostrou que a cafeÃna e o CSC reverteram Ãs alteraÃÃes comportamentais e neuroquÃmicas da 6-OHDA, apresentando efeitos possivelmente benÃficos no tratamento da DP. / Parkinson disease (PD) is a neurodegenerative disorder characterized by loss of dopaminergic neurons in the substantia nigra pars compacta. Antagonists of the A2A subtype of adenosine receptor have emerged as a target for nondopaminergic antiparkinsonian agents. The present work showed the effects of caffeine and 8-(-3-chlorostyryl)-caffeine (CSC), A2A receptors antagonists, on behavior and biochemical alterations in 6-OHDA-lesioned rats, as a model of PD. Animals (male Wistar rats, 260-280 g) were injected daily with caffeine (10 and 20 mg/kg,i.p., 1h after 6-OHDA lesion for 14 days or six days after 6-OHDA lesion for 7 days), or CSC (1 and 5 mg/kg, i.p., 1h after 6-OHDA lesion for 7 days) alone or associated with L-DOPA (CSC 1 mg/kg, i.p. + L-DOPA 50mg/kg + Benzerazida 12,5 mg/kg, i.p., six days after 6-OHDA lesion for 7 days). Fourteen days after 6-OHDA, the animalsâ behavior was assessed by monitoring body rotations induced by apomorphine (3 mg/kg, i.p.). The results showed that the drastic increase in body rotation, induced by the 6-OHDA lesion, after the apomorphine challenge, was significantly (50 times) and dose-dependently reversed by CSC or caffeine. The decreased striatal levels of DA and metabolites, in the 6-OHDA-lesioned rats (75-85%), were blocked after caffeine or CSC alone or in association with L-DOPA treatment as well as the concentrations of NE, 5-HT and 5-HIAA. These effects were potentiated in 6-OHDA-lesioned animals treated with the association of CSC and L-DOPA. Concentrations of the amino acids glutamate and GABA were significantly increased (3.8 and 3 times, respectively) in the 6-OHDA-lesioned rat striatum. Similarly, CSC also reversed these alterations significantly. We also demonstrated protective effects against 6-OHDA-induced cytotoxicity in rat mesencephalic cells. Caffeine or CSC significantly increased the number of viable cells after their exposure to 6-OHDA, as measured by the MTT assay. While nitrite levels and lipid peroxidation in the cells were drastically increased by 6-OHDA, its concentration was brought toward normality after caffeine or CSC. 6-OHDA decreased the number of normal cells while increasing the number of apoptotic cells. Caffeine or CSC, significantly recovered the number of viable cells, and decreased the number of apoptotic cells, as compared to the group treated with 6-OHDA alone. Interestingly, while a significant lower number of activated microglia was seen after cells exposure to caffeine plus 6-OHDA, this was not the case after cells exposure to CSC plus 6-OHDA. While caffeine lowered the percentage of reactive astrocytes increased by 6-OHDA, CSC showed not effect. These results showed a strong neuroptrotection afforded by caffeine or CSC on rat mesencephalic cells exposed to 6-OHDA. In conclusion, we showed that CSC or caffeine reversed behavior and biochemical alterations, observed in the 6-OHDA-lesioned rats, pointing out to the potential benefit of A2A receptors antagonists as non-dopaminergic therapeutic targets for the treatment of PD.

A avaliação neuropsicológica de portadores de doença de Parkinson (DP) tem sido de fundamental importância para definição de resultados em procedimentos clínicos, cirúrgicos experimentais ou para diagnóstico de demência nestes doentes. No entanto, ainda não existe consenso quanto aos testes neuropsicológicos necessários e padrões de comprometimento esperados. Este estudo objetivou comparar a produtividade das funções neuropsicológicas entre portadores da Doença de Parkinson, em diferentes estágios da doença, em relação aos indivíduos normais. Foram analisados 60 sujeitos (32 homens e 28 mulheres), emparelhados em relação à idade (média de 65,6 +-9,2) e instrução (média de 5,9 =- 4,0), distribuídos entre normais (n=20) e portadores de DP ambulatoriais, nos estágios leve a moderado (n=20) ou moderado a grave (n=20), de acordo com a escala Hoehn & Yahr. A bateria utilizou 24 testes neuropsicológicos abrangendo as funções de raciocínio, percepção visuoespacial, visuoconstrução, linguagem, memória, atenção e função executiva. Os resultados apontaram diferenças significantes (p < 0,01) entre vários testes e em todas as funções, exceto linguagem. Alguns instrumentos se mostraram mais adequados e outros se mostraram pouco indicados para avaliar estes doentes. Diferenças entre os estágios da doença só se evidenciaram nos testes que exigiam destreza motora. Este trabalho estabelece a adequação dos instrumentos e propõe uma bateria específica para avaliação destes doentes. A investigação de estados situacionais (nível cultural, sintoma afetivo e/ou limitações funcionais), manifestos na avaliação, permitiu estabelecer parâmetros para discriminar o modo como estas variáveis interferem na produção dos doentes de Parkinson. E conclui-se apresentando um método inovador de classificação para subsidiar com objetividade o diagnóstico neuropsicológico diferencial na DP. / The neuropsychological assessment of patients with Parkinson disease (PD) has been very important to define the results in clinical, experimental surgeries procedures or in the diagnostic of dementia of these patients. However, there is no consensus about the necessary neuropsychological tests and about the expected commitment patterns. This study aimed to compare the productivity of the neuropsychological functions among patients with Parkinson Disease, in different stages of the disease, in relation to normal people. Sixty subjects were assessed (32 men and 28 women), pared in relation to the age (average of 65.6 +- 9.2) and age of study (average of 5.9 +- 4.0), distributed among normal (n=20) and outpatients with PD, in the mild to moderate stages (n=20) or moderate to severe (n=20), according to Hoehn & Yahr Scale. The battery used 24 neuropsychological tests comprising the thinking, visuospatial perception, visuoconstruction, language, memory, attention and executive function. The results showed significant differences (p < 0.01) among many tests and in all the functions, except language. Some instruments were more suitable and others proved to be less indicated to assess these patients. Differences in the stages of the disease were highlighted in the tests that required motor ability. This work establishes the adequacy of the instruments and proposes a specific battery to assess these patients. The investigation of the situational state (cultural level, affective symptom and/or functional limitations), that appeared in the assessment, allowed to establish parameters to find out the way that these variables interfered in the Parkinson patients’ production. The work concludes presenting an innovative classification method to objectively subside the neuropsychological differential diagnosis for PD.

Alterações fonoarticulatórias caracterizam a disartria hipocinética e podem ocorrer ao longo da evolução da doença de Parkinson (DP). No entanto, não existem estudos que evidenciem a influência da idade nessas alterações. Objetivo: Comparar e correlacionar selecionadas características fonoarticulatórias em pacientes com DP de início na meia idade e tardio. Método: Participaram 50 pacientes que constituíram dois grupos. O Grupo I foi composto por 30 (60%) pacientes com idade de início da DP entre 40 e 55 anos e o Grupo II, por 20 (40%) pacientes com início da doença após os 65 anos, ambos com a duração da doença variando de 2 a 18 anos. Todos foram submetidos à avaliação neurológica a partir da Parte III da Escala Unificada para a Doença de Parkinson (UPDRS) e Escala Modificada de Hoehn & Yahr e, fonoaudiológica, realizada por meio de análise perceptivo-auditiva (velocidade, inteligibilidade e tipo articulatório da fala e qualidade da voz) e acústica computadorizada (freqüência fundamental e intensidade da voz). Resultados: Não houve diferença estatisticamente significativa entre os dois grupos no que diz respeito ao estágio da doença, aos escores da escala UPDRS e às análises fonoaudiológicas. As análises de correlação não mostraram diferença estatisticamente significativa entre a qualidade, a freqüência fundamental e a intensidade da voz, bem como a velocidade da fala e o estágio da doença. Contudo, houve diferença estatística significativa entre a articulação e a inteligibilidade da fala e o estágio da doença. Os escores da escala UPDRS não revelaram diferença estatisticamente significativa quando comparados com a qualidade, a freqüência fundamental e a intensidade da voz e a velocidade da fala. Diferença estatisticamente significativa foi encontrada na correlação entre a articulação e os acometimentos axiais e também entre a velocidade da fala e os escores dos acometimentos axiais, da rigidez e da bradicinesia. Conclusões: A idade de início da DP não se relacionou com as características fonoarticulatórias analisadas. A função articulatória (articulação e inteligibilidade da fala) estava prejudicada sobremaneira nos estágios mais avançados da DP e foi associada ao maior tempo de duração da doença e aos escores mais elevados de manifestações axiais, de rigidez e de bradicinesia. A função fonatória (freqüência fundamental, qualidade e intensidade da voz) apresentou-se com características semelhantes em todos os estágios da DP e não se associou com a duração da doença e tampouco com os escores motores analisados. / Parkinson\'s disease (PD) patients may develop speech and voice abnormalities during the course of their illness, typically hypokinetic dysarthria. There are no studies to date describing the influence of age on these abnormalities. Objective: To describe and to correlate selected speech and voice characteristics in PD patients with middle-age and late-onset disease and compare each group\'s findings. Methods: Fifty PD patients were enrolled in this study and subsequently divided into two groups. Group I included 30 (60%) patients with PD onset between 40 and 55 years old and Group II consisted of 20 (40%) patients with disease onset after the age of 65. In both groups disease duration ranged from 2 to 18 years. All patients were submitted to neurological evaluation based on the motor Unified Parkinson\'s Disease Rating Scale (UPDRS - part III) and the Modified Hoehn and Yahr Staging Scale plus speech and voice evaluation, performed through perceptual analysis (speech velocity and intelligibility, articulatory speech type and voice quality) and computerized acoustic (fundamental frequency and voice intensity). Results: There was no statistically significant difference between the groups concerning disease stage, UPDRS scores and speech and voice analysis. Disease stage was not associated to quality, fundamental frequency and intensity of voice. There was also no difference between speech velocity and disease stage. On the other hand, there was statistically significant difference between articulation and speech intelligibility and disease stage. UPDRS scores did not reveal a statistically significant difference when compared to quality, fundamental frequency and voice intensity and speech velocity, but there was a difference in the correlation between articulation and axial symptoms and also between speech velocity and scores for axial symptoms, rigidity and bradykinesia. Conclusion: The age of onset of PD was not associated with speech and voice characteristics analysed. Articulatory function (speech articulation and intelligibility) was remarkably affected in advanced PD and was associated with not only with longer disease duration, but also with more axial symptoms, rigidity and bradykinesia. Phonatory function (fundamental frequency, quality and intensity of voice) disclosed similar characteristics in all PD stages and was not associated with disease duration or with motor scores analysed.

Abstract Parkinson’s disease (PD) is a chronic and progressive neurodegenerative disease which is characterized by resting tremor, rigidity, bradykinesia and postural instability. Advanced PD is often complicated by falls, immobilisation and progressive deterioration of overall physical capability that may jointly contribute to a reduced quality of life and even to increased mortality. The purpose of this study was to identify risk factors for falls and mortality in PD, to assess the clinical correlates of balance and mobility, and to evaluate the association between orthostatic hypotension (OH), balance and mobility. From a total population of approximately 205 000 inhabitants, 125 patients with idiopathic PD were included in the study. Baseline medical data including occurrence of recent falls were collected, and patients were clinically tested for balance, mobility and orthostatic blood pressure reactions. Falls were thereafter prospectively recorded for two years using fall diaries and follow-up calls. Mortality was documented by reviewing the hospital charts four years after the baseline examination. In the cross-sectional part of the study, one-third of the patients reported recent falling. Disease duration and severity, recent falling and use of a walking aid were predictors of increased postural sway in PD. Advanced age and severity of the disease were related to impaired balance and mobility in PD patients. Severity of the disease and increased postural sway were independent risk factors for recent falling in PD, whereas measures of mobility were less important in this manner. Fifty-three percent of the patients had OH in the orthostatic test. Patients with OH had significantly increased postural sway in standing compared to patients without OH. On the contrary, OH was not associated with mobility and walking speed. In the present data, OH was not associated with the risk of falling in PD. Sixty-three percent of the study patients experienced falls and almost half of the subjects fell recurrently during the two-year follow-up. History of falling and disease severity indicated increased risk of recurrent falls in PD, while patients with slow walking speed had an increased risk of mortality. The results show that balance impairment and falls are common features in PD. Slow walking speed may be associated with increased mortality in PD.

In neurologic disorders, there are progressive losses in regional brain structural integrity, circuitry, and neuronal process that threaten individuals' ability to express functional capacity at several levels of severity. The classification of (a) patients on the basis of diagnosis, risk prognosis, and intervention outcome forms the basis of clinical staging and (b) laboratory animals on the basis of animal model of brain disorder, extent of insult and dysfunctional expression, provides the components for the clinical staging and preclinical staging, respectively, of the disease state with certain associated epidemiological, biological, and genetic characteristics. The investigation of epigenetics and biomarkers is intrinsic to any analysis of the progressive nature of the neurogenerative disorders, in the present account disorders relating to Alzheimer's disease, Parkinson's disease, depression, and diabetes.

Indiana University-Purdue University Indianapolis (IUPUI) / Parkinson disease (PD) is the second most common neurodegenerative disease. It is characterized by loss of dopaminergic cells in the substantia nigra, which causes loss of dopaminergic synapses onto striatal medium spiny neurons (MSNs). Dendritic spines that are localized to these striatal MSNs receive synaptic inputs from both the nigral dopamine neurons and cortical glutamate neurons. Signaling downstream of excitatory, glutamatergic drive is modulated by dopamine. This tripartite connection: glutamate, dopamine, and MSN dendritic spine, is important for normal motor function. Glutamate released from presynaptic terminals binds to and activates two classes of inotropic glutamate receptors that are localized to dendritic spines on striatal MSNs: the α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR) and the N-methyl-D-aspartate receptor (NMDAR). Once these receptors are activated, they allow for Ca2+ influx, which in turn activates Ca2+-dependent processes that underlie neural plasticity, including long-term potentiation (LTP) and long-term depression (LTD). Proper machinery in the pre- and post-synaptic neurons is required for normal signal transduction. Moreover, this signal transduction requires proper organization of synaptic proteins, which is achieved by specific protein-protein interactions. These protein-protein interactions are dynamic and can be modulated under various conditions, including pathological changes in the phosphorylation status of a specific protein. Catalytically active proteins called phosphatases and kinases specifically regulate the phosphorylation status of synaptic proteins. Pathologically, in PD there is increased autophosphorylation and activation of Ca2+/calmodulin-dependent protein kinase II (CaMKII). This increased phosphorylation may be due to changes in the activity of the serine/threonine protein phosphatase 1 (PP1), a highly conserved protein serine/threonine phosphatase that has a diverse set of functions in eukaryotes. Serine/threonine phosphatase substrate specificity is obtained via interactions with targeting and regulatory proteins. One such protein, spinophilin, is a scaffolding protein that targets PP1 to various synaptic substrates to regulate their phosphorylation. Interestingly, the association of PP1 with spinophilin is enhanced in a rat model of PD. The NMDAR is another protein that has altered phosphorylation in animal models of PD. We have found that there is a decrease in the NMDAR-spinophilin interaction in an animal model of PD. Here, we have found that spinophilin and the NMDAR interact in brain tissue and when overexpressed in a mammalian cell system. Moreover, we have identified novel mechanisms that regulate this interaction and have identified putative consequences of altering this association. These studies give us novel insight into mechanisms and consequences underlying pathological changes observed in an animal model of PD. Understanding these changes will inform novel therapeutic targets that may be useful in modulating striatal function.