La maladie de Parkinson (MP) est la deuxième maladie neurodégénérative la plus fréquente touchant 3 % de la population âgée de 65 ans et plus. La perte neuronale au niveau de la substantia nigra (SN) et induisant une réduction de la dopamine (DA) striatale ainsi que la présence d'agrégats formées principalement de la protéine α-Synuclein (α-Syn) caractérisent la MP. Bien que le diagnostic clinique soit basé sur la présence de déficits moteurs spécifiques, la MP est également associée à des dysfonctionnements de divers mécanismes cellulaires, notamment la dégradation de α-Syn, la fonctionnalité mitochondriale, le trafic axonal, la réponse neuroinflammatoire et l'augmentation du stress oxydatif. Jusqu'à présent, aucune thérapie n'est en mesure de ralentir et/ou de restaurer la dégénérescence neuronale. Les traitements actuellement utilisés se basent principalement sur le remplacement pharmacologique de la DA striatale et sont accompagné d'approches non-dopaminergiques, ciblant, par exemple, les récepteurs adrénergiques et sérotoninergiques pour mieux traiter les symptômes moteurs et non-moteurs. Des stratégies non-pharmacologiques, telles que la stimulation cérébrale profonde (SCP), ont permis une meilleure prise en charge des personnes qui ne répondent plus aux traitements pharmacologiques classiques. Des thérapies expérimentales en cours tentent, quant à elles, de restaurer la DA striatale par des approches génétiques et cellulaires, et plus récemment, des études cliniques évaluant de nouvelles stratégies basées sur l'agrégation de l'α-Syn et le transport cellulaire ont vu le jour. Deux défis majeurs demeurent toujours: 1) Identifier de nouveaux composés capables de ralentir, de sauver et/ou d'induire la régénérescence des neurones et 2) identifier des biomarqueurs caractéristiques de la phase prodromique de la maladie permettant des interventions précoces. Parmi les différents candidats potentiels présentant un tel effet, notre laboratoire a identifié une molécule, la cystamine, et son métabolite actif, la cystéamine. Tous deux ont déjà été testés chez l'homme pour d'autres indications, telle que pour la maladie de Huntington (MH). Les molécules cystamine/cystéamine agissent par de multiples voies jugées critiques à la pathogenèse de la MP. En particulier, la cystamine est capable de traverser la barrière hémato-encéphalique. De plus, les molécules cystamine/cystéamine peuvent favoriser la sécrétion de facteurs neurotrophiques, inhiber le stress oxydatif et réduire les réponses inflammatoires. Au cours des dernières décennies, notre laboratoire a cumulé plusieurs données suggérant que les molécules cystamine/cystéamine peuvent ralentir, et même inverser les processus neurodégénératifs induits dans de nombreux modèles de la MP. Afin d'approfondir nos connaissances sur les potentiels bénéfiques de l'utilisation de la cystéamine dans la MP, nous avons testé ce composé sous conditions in vivo. Nous avons utilisé des souris transgéniques Thy1-α-Syn présentant une pathogenèse progressive de type MP, accompagnés d'importants déficits moteurs et tout particulièrement, de la voie nigrostriée. L'utilisation de ce modèle nous a permis d'évaluer si un traitement à la cystéamine pouvait avoir un impact sur l'accumulation de l'α-Syn humaine et son implication dans la formation de corps de Lewy. Les résultats obtenus ont montré que le médicament peut améliorer les capacités motrices des souris traitées, présentant entre autres une action spécifique sur la voie nigrostriée. Cet effet peut être partiellement dû à la réduction des niveaux d'α-Syn de type « sauvage » et d'autres formes de la protéine (phosphorylée et filamentée) détectées par des analyses post-mortem chez les souris traitées. L'effet thérapeutique de la cystéamine a également été démontré in vitro en utilisant des neurones dopaminergiques (DAergiques) dérivés de cellules souches pluripotentes induites d'un patient atteint de la MP et porteur de la triplication du gène SNCA. Cette étude a montré l'activité bénéfique de la cystéamine dans la restauration des ramifications neuronales et dans l'augmentation de la viabilité cellulaire des neurones DAergiques exposés à la neurotoxine 6-hydroxy-DA. Les résultats présentés ici, ainsi que ceux de nos études antérieures, suggèrent des propriétés bénéfiques de la cystéamine à l'égard de plusieurs marqueurs de la MP ainsi que des capacités à modifier le cours évolutif de la maladie. / Parkinson's disease (PD) is the second most common neurodegenerative disorder affecting 3% of the population aged 65 years of age and older. The disease hallmarks include neuronal loss at the level of the substantia nigra (SN) that leads to a decrease in striatal dopamine (DA) and the presence of inclusions mainly composed of the protein α-Synuclein (α-Syn). Although clinical diagnosis is based on the appearance of motor deficits, PD also presents with a number of non-motor symptoms that worsen the patient's quality of life. Neuropathologically, PD is characterized by the malfunction of various cellular mechanisms including α-Syn degradation, mitochondrial function, axonal trafficking, neuroinflammation and increased oxidative stress. To date, not a single compound/approach has shown the capacity to reverse or slow down neuronal degeneration. Therefore, PD therapy is still anchored to the pharmacological replacement of striatal DA levels and is often accompanied by non-dopaminergic approaches targeting, for example, the adrenergic and serotoninergic receptors, to better manage motor and non-motor symptomatology. Non-pharmacological strategies, such as deep brain stimulation (DBS), have allowed better symptomatic management, especially for individuals developing intractable motor contraindications due to DA replacement therapy. Promising experimental therapies have attempted to re-establish striatal DA through gene and cell-based strategies. More recently, new strategies targeting α-Syn aggregation and cellular transport have entered clinical trials. The most significant challenges in PD research include the: 1) identification of new disease-modifying agents able to slow down, rescue and/or induce regeneration of dying neurons and the 2) identification of biomarkers for the prodromal disease stages, which would allow early intervention. Among the various potential candidates displaying disease-modifying proprieties, our laboratory has identified cystamine, and its active metabolite cysteamine, already under trial in humans for other clinical indications, including another neurodegenerative disorder, Huntington's disease (HD). The molecule cystamine/cysteamine acts via multiple pathways that have been determined critical to the pathogenesis of PD. In particular, cystamine is capable of crossing the blood-brain barrier, and both agents (cystamine and cysteamine) can promote the secretion of neurotrophic factors, inhibit oxidative stress and reduce inflammatory responses. Over the last decade, our laboratory has accumulated compelling evidence that both cystamine and cysteamine can halt, and even reverse, ongoing neurodegenerative processes in various PD models. To expand our knowledge on the potential efficacy of cysteamine to treat PD, my thesis focused on testing the drug in vivo using the Thy1-α-Syn transgenic mouse model that displays a progressive PD-like pathogenesis and a number of behavioural motor deficits due to an age-related impairment of the nigro-striatal pathway. The use of this model has also allowed us to investigate whether treatment with cysteamine could impact the accumulation of human α-Syn and its related forms involved in Lewy body formation. The results obtained have shown how the drug can improve the motor skills of treated mice and specificity of action towards the nigro-striatal pathway. This effect may be partially due to the reduction of wild type (WT) α-Syn levels and other forms of the protein, e.g. phosphorylated and filamented that were detected in post-mortem analyses of the treated mice. The potential therapeutic effect of cysteamine on DA neurons has further been demonstrated in vitro using induced pluripotent stem cell- (iPSC) derived dopaminergic (DAergic) neurons from a PD patient carrying a triplication of the SNCA gene. This study showed the ability of the drug to restore neurite ramifications and increase cell viability of dying DAergic neurons exposed to the neurotoxin 6-hydroxy-DA. The findings herein, presented together with results from our previous investigations, suggest the potential efficacy of cysteamine towards multiple PD hallmarks as well as disease-modifying properties.

La maladie de Parkinson (MP) est une maladie neurologique progressive caractérisée par des dysfonctionnements moteurs se manifestant par des tremblements, de la bradykinésie, de la rigidité musculaire ainsi que de l’instabilité posturale. Ces manifestations physiques sont causées par la dégénérescence des neurones dopaminergiques (DAergiques) de la voie nigrostriatale. Ces dysfonctions motrices sont généralement précédées, jusqu’à 10 ans avant leur apparition, par d’autres symptômes, dont des altérations gastro-intestinales. La dégénérescence des neurones DAergiques dans le plexus myentérique serait à l’origine des dysfonctions gastro-intestinales. Plusieurs problématiques associées à la MP peuvent entraver la découverte de nouvelles cibles thérapeutiques. D’abord, les causes menant à l’initiation de la pathologie et la neurodégénérescence demeurent largement inconnues, et ce, malgré la mise en évidence de certains mécanismes impliqués dans la pathogenèse de la maladie, dont l’inflammation. Un second obstacle constitue le manque de biomarqueurs permettant le diagnostic précoce de la maladie au cours de son développement, puisque la pathologie se manifeste lorsque la dégénérescence atteint 60 à 70% des neurones DAergiques. Conséquemment, les traitements disponibles actuellement concernent uniquement les options thérapeutiques symptomatiques tandis qu’aucun traitement n’est disponible afin de modifier le cours évolutif du processus dégénératif amorcé plusieurs années avant le diagnostic. Ce projet doctoral s’inscrit donc dans une thématique globale ciblant plusieurs aspects de la problématique soulevée ci-dessus, en s’attardant principalement à mieux comprendre la contribution du système immunitaire innée dans la dégénérescence des neurones au niveau du plexus myentérique dans un modèle de souris parkinsoniennes. En premier lieu, nous avons caractérisé la réponse immunitaire engendrée par la neurotoxine 1-méthyl-4-phényl-1,2,3,6- tétrahydropyridine (MPTP) dans le plexus myentérique de souris sauvages et partiellement déficientes en immunité innée (MyD88 -/-) La découverte de l’infiltration de monocytes proinflammatoires dans le plexus myentérique nous a menés à étudier le rôle de ce type cellulaire dans l’altération des neurones DAergiques au niveau du plexus myentérique et du système nerveux central de souris traitées au MPTP. Les résultats obtenus nous ont permis de tester une nouvelle cible thérapeutique permettant de moduler la réponse inflammatoire afin de limiter les dommages neuronaux induits par la neurotoxine. / Parkinson’s disease (PD) is a progressive neurological disorder characterized by motor dysfunctions, which include tremor, muscle rigidity, postural instability and bradykinesia. The slow and progressive degeneration of dopaminergic (DAergic) neurons of the nigrostriatal pathway constitutes a key element at the origin of clinical motor manifestations. Non-motor symptoms are also observed and could preceed their motor counterparts by several years. The former include gastrointestinal problems such as delayed gastric emptying, constipation and defecatory dysfunctions. The degeneration of DAergic neurons in the myenteric plexus is at the origin of gastrointestinal impariments. Major issues encountered in PD research currently impede the development of appropriate medication. First, the factors behind PD initiation that lead to neurodegeneration remain largely unknown, despite the discovery of several mechanisms involved in its pathogenesis, notably inflammation, which has been given considerable attention in recent years. A second hurdle is the lack of biomarkers to diagnose the disease earlier in its development. Indeed, most motor symptoms are manifested when approximately 60 to 70 % of DAergics neurons are degenerated. As a result of these caveats, PD patients currently only have access to symptomatic treatment options, since no therapy is available to modify degenerative processes primed several years before diagnosis. My doctoral research project is built into a global thematic approach targeting several aspects of the issues raised above, but more specifically to investigate the role of the innate immune response and the contribution of macrophages to neuronal degeneration in the myenteric plexus in a murine model of PD. First we characterized the innate immune response occurring in the enteric nervous system secondary to 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) lesioning of wild-type and immune deficient (MyD88 -/-) mice. Our findings about proinflammatory monocytes infiltration in the myenteric plexus lead us to investigate on the role of the innate immune response relatively with neurodegeneration occurring in the central nervous system and myenteric plexus in response to MPTP. Our promising results provide us with the chance to test a new therapeutic target that modulates the innate immune response and limits MPTP-induced neuronal damages.

Pathological studies on Parkinson's disease (PD) patients suggest that PD pathology progresses from the enteric nervous system (ENS) and the olfactory bulb into the central nervous system. We have previously shown that environmental toxins acting locally on the ENS mimic this PD-like pathology progression pattern in mice. Here, we show for the first time that the resection of the autonomic nerves stops this progression. Moreover, our results show that an environmental toxin (i.e. rotenone) promotes the release of alpha-synuclein by enteric neurons and that released enteric alpha-synuclein is up-taken by presynaptic sympathetic neurites and retrogradely transported to the soma, where it accumulates. These results strongly suggest that pesticides can initiate the progression of PD pathology and that this progression is based on the transneuronal and retrograde axonal transport of alpha-synuclein. If confirmed in patients, this study would have crucial implications in the strategies used to prevent and treat PD.

Objetivo: Identificar el perfil clínico de la Enfermedad de Parkinson en pacientes atendidos en consulta externa del servicio de neurología del Hospital Nacional Alberto Sabogal Sologuren durante el periodo Enero-Diciembre del año 2013. Materiales y métodos: Se realizó un estudio descriptivo, retrospectivo de corte transversal en el Hospital Nacional Alberto Sabogal Sologuren, donde se revisaron las Historias clínicas de los pacientes con Enfermedad de Parkinson atendidos en los consultorios del Servicio de Neurología durante el año 2013. Los datos fueron recolectados en una ficha electrónica de Microsoft Office Excel versión 2010, para su posterior transferencia y procesamiento SPSS versión 19.0. Resultados: Después de la revisión de las historias clínicas, 134 pacientes cumplieron con los criterios de inclusión, evidenciándose en ellos un predominio masculino (1.68/1), con una frecuencia de 84 varones (62.7%), con una edad promedio de 72,37. El síntoma predominante fue rigidez en 93 pacientes (69,4%), seguido de temblor de reposo en 86 pacientes (64,2%) y bradicinesia en 57 pacientes (42,5%). La afectación inicial de los síntomas fue a predominio de miembro superior derecho con un 69,4% de pacientes. Dentro de los síntomas no motores se observó que la afectación principal fue la del sueño en 68 pacientes (62,4%), seguida de depresión en 26 pacientes (23,9%). Dentro de los síntomas autonómicos tenemos que 55 pacientes (55,6%) presentaron alteraciones gastrointestinales y de estos pacientes 36 (26,9%) presentaron constipación, 15 (11,2%) pacientes presentaron disfagia y 4 (3%) pacientes ambas patologías. Conclusiones: Se presentan las características clínicas de pacientes con enfermedad de Parkinson, revelando el estudio un predominio del sexo masculino similar a otros estudios, con edad promedio dentro del rango reportado en la mayoría de literaturas. La mayoría presentó afección en miembro superior derecho. Si bien los síntomas cardinales fueron rigidez, bradicinesia y temblor, se observó que un alto porcentaje presento también síntomas que engloban diversos factores neurobiológicos como alteraciones del sueño y depresión, asimismo alteraciones autonómicas como la constipación.

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.

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.

Orientador: Lilian Teresa Bucken Gobbi / Banca: Carolina Rodrigues Alves Silveira / Banca: Renato de Moraes / Banca: Carla da Silva Batista / Banca: Luciane Aparecida Pascucci Sande de Souza / Resumo: Introdução: A presente tese de Doutorado é composta por dois estudos. O objetivo do Estudo #1 foi investigar a associação entre domínios do andar (com e sem tarefa dupla) e domínios cognitivos e neuropsiquiátricos de pacientes com DP (DP). O objetivo do Estudo #2 foi investigar os efeitos de uma intervenção de atividades rítmicas e dança no andar, funções cognitivas e aspectos neuropsiquiátricos de pacientes com DP e a manutenção de benefícios após um período de follow up (5 meses). Materiais e método: O Estudo #1 contou com a participação de 87 pacientes com DP. Após avaliação clínica e anamnese, os pacientes foram avaliados quanto ao andar (com e sem tarefa dupla), funções cognitivas e aspectos neuropsiquiátricos. A partir das avaliações, dois modelos foram elaborados: i) modelo do andar formado por 16 características espaço-temporais do andar, distribuídos em cinco domínios (pace, variabilidade, ritmo, assimetria e controle postural); ii) modelo de aspectos cognitivos e neuropsiquiátricos formado por 10 testes, distribuídos em sete domínios (cognição global, memória, função executiva, atenção, memória de trabalho, habilidade visuoespacial, neuropsiquiátrico ). O Estudo #2 contou com a participação de 86 pacientes com DP que foram distribuídos randomicamente em dois grupos: grupo de atividades rítmicas (DPd) e dança e grupo convívio (DPc). As atividades do grupo DPd foram realizadas com base em diferentes estilos, com progressão tanto em mudanças do ambiente como em complex... (Resumo completo, clicar acesso eletrônico abaixo) / Abstract: Introduction: This PhD thesis consists of two studies. The aim of the Study #1 was to investigate the association between gait domains (with and without dual task) and cognitive and neuropsychiatric domains of patients with Parkinson's disease (PD). The aim of the St udy #2 was to investigate the effects of a rhythm activities and dance intervention on gait, cognitive function and neuropsychiatric aspects of patients with PD, as well as the retention of benefits after a follow up period (5 months). Methods: Study #1 in volved the participation of 87 patients with PD. A fter clinical assessment, gait (with and without dual task), cognition and neuropsychiatric aspects were assessed. Gait, cognition and neuropsychiatric aspects were summarized in two models: i) a gait model with 16 spatial - temporal gait characteristics, described by five domains (pace, variability, rhythm, asymmetry and postural control); ii) a cognitive and neuropsychiatric model with 10 assessments organized in seven domains (global cognition, memory, exec utive function, attention, working memory, visuospatial ability and neuropsychiatric). Study #2 involved 86 patients with PD which were allocated in two groups: rhythm activities and dance intervention group (PDd) and socializing group (PDs). Activities of the PDd group were structured based on different styles of dance, with progression in the environment and movement complexity. Activities of t he PDs group were organized in three phases: i) talks and d... (Complete abstract click electronic access below) / Doutor

Diss. (sammanfattning) Stockholm : Karolinska institutet, 2009.

Thèse (M.Sc.) -- Université Laval, 1996. / Bibliogr.: f. 43-53. Publ. aussi en version électronique.

Thèse (M.Sc.)--Université Laval, 2001. / Bibliogr.: f. [92]-105. Publ. aussi en version électronique.