p. 1-68 / Submitted by Antonio Geraldo Couto Barreto (ppgms@ufba.br) on 2013-10-04T11:15:07Z No. of bitstreams: 1 TESE NEUROPATIA PERIFERICA NA DPI-GRACAS.pdf: 925860 bytes, checksum: accf87e5eb47a69b54a193d8b77c2a6b (MD5) / Approved for entry into archive by Patricia Barroso(pbarroso@ufba.br) on 2013-10-08T17:02:06Z (GMT) No. of bitstreams: 1 TESE NEUROPATIA PERIFERICA NA DPI-GRACAS.pdf: 925860 bytes, checksum: accf87e5eb47a69b54a193d8b77c2a6b (MD5) / Made available in DSpace on 2013-10-08T17:02:06Z (GMT). No. of bitstreams: 1 TESE NEUROPATIA PERIFERICA NA DPI-GRACAS.pdf: 925860 bytes, checksum: accf87e5eb47a69b54a193d8b77c2a6b (MD5) Previous issue date: 2013 / Palavras-chaves: 1.; 2.; 3.; 4.; 5..1.; 2.; 3.levodopa; 4., 5.homocysteine. / Indivíduos com doença de Parkinson idiopática (DPI) podem apresentar neuropatia periférica, o que pode agravar o desempenho motor. A causa da neuropatia periférica nesses pacientes é controversa. Objetivos- Identificar a prevalência de polineuropatia periférica (PNP) e os fatores que contribuem para seu surgimento na DPI. Métodos- Corte transversal com grupo controle. Foram avaliados 66 indivíduos: 36 com doença de Parkinson e 30 controles quanto à presença de polineuropatia pelos Escores de Toronto (ET), de Sintomas (ESN) e de Comprometimento Neuropáticos (ECN), e pela Eletroneuromiografia (EMG). Investigou-se a possível associação entre níveis séricos aumentados de homocisteína (HCI), hipovitaminose B12 (VB12), e diminuição de ácido fólico no soro, uso da levodopa, a gravidade da doença de Parkinson e a PNP. Resultados- O grupo Parkinson foi composto por 16M/20F [idade 69,4±6,8 anos] e os controles por 12M/18F[idade 70,5±6,1 anos]. A maioria dos participantes apresentou escores clínicos sugestivos de neuropatia, ET [controles 3,8±2,6; DPI 5,3±1,8, p=0,012], ECN [controles 3,0±2,3; DPI 4,2±1,7, p=0,026], alterações neuropáticas no estudo condução nervosa sensitiva e motora dos nervos sural e fibular ocorreu em 3% dos controles e em 8% dos pacientes com DPI. Embora a HCI tenha sido mais alta nos DPI, a diferença não foi significante [DPI 16,01±6,88 mmol/L; controles 14,68±5,77 mmol/L, p=0,403]; níveis baixos de VB12 foram mais frequentes nos controles 30% vs 19,4%, p=0,961. Não houve associação entre as dosagens bioquímicas (coef.associação= 0,30), nem entre o uso de levodopa (Phi= 0,533) e a PNP, que esteve associada a DPI (RC=2,64). Conclusão- Na nossa amostra, os escores neuropáticos foram mais altos entre os portadores de DPI e não esteve associado ao uso da levodopa nem a hiperhomocisteinemia e/ou deficiência da vitamina B12. / Salvador

Parkinson’s disease (PD) is the second most common neurodegenerative disease affecting 2% of the population over 65 years old that lacks effective cure. The current available treatments for PD are largely symptomatic and palliative. Tianma Gouteng Yin (TGY) is a traditional Chinese medicine (TCM) formula belongs to the formulas that dispel wind. Nowadays, it has been a commonly prescribed formula to treat Parkinsonian-like symptoms such as tremor and paralysis in some of the patients. However, just as most of the TCM formula, the material basis and the underlying pharmacological effects of TGY are still lacking experimental evidence. In this study, a method using UHPLC/Q-TOF-MS and HPLC-ELSD has been developed and successfully applied to qualitatively and quantitatively determine the complex phytochemicals of TGY. Totally 28 phytochemicals were identified, of which 20 were simultaneously quantified. The material basis profile of TGY decoction was delineated for the first time. After full component analysis of TGY, the neuroprotective activity of TGY was verified both in vivo and in vitro. In Drosophila PD models, TGY mitigated rotenone induced toxicity and promoted α-synuclein clearance. In stereotaxic rotenone intoxication rats, TGY exerted neuroprotective effects in terms of preventing dopaminergic neurons loss and alleviating neuroinflammation. TGY alleviated rotenone induced apoptosis in SH-SY5Y cells. Furthermore, we discovered that Geniposide, an important component of TGY, is an autophagy inducer both in vivo and in vitro and is neuroprotective in transgenic Drosophila PD model. In general, our study proves that TGY is neuroprotective in PD models. In addition to the efficacy study, safety of TGY application in terms of TGY-drug interaction was also evaluated. In our study, herb-drug interactions between TGY and one of the most popular drugs used in PD treatment, Sinemet, were studied. The pharmacokinetics data showed that co-administration of TGY could suppress the absorption of Levodopa, the main component of Sinemet, for the first time. This information suggest that in clinical practice, TGY should avoid been administrated with Levodopa containing medicaments at the same time. In conclusion, the data of this study provides valuable information on the material basis, efficacy and safety of TGY. This information is useful reference for the clinical application of TGY in PD treatment. Keywords: Tianma Gouteng Yin, Parkinson’s disease, Drosophila, Rotenone, -synuclein, Geniposide, Autophagy, Sinemet, Herb-drug interaction

The understanding and treatment of brain disorders as well as the development of intelligent machines is hampered by the lack of knowledge of how the brain fundamentally functions. Over the past century, we have learned much about how individual neurons and neural networks behave, however new tools are critically needed to interrogate how neural networks give rise to complex brain processes and disease conditions. Recent innovations in molecular techniques, such as optogenetics, have enabled neuroscientists unprecedented precision to excite, inhibit and record defined neurons. The impressive sensitivity of currently available optogenetic sensors and actuators has now enabled the possibility of analyzing a large number of individual neurons in the brains of behaving animals. To promote the use of these optogenetic tools, this thesis integrates cutting edge optogenetic molecular sensors which is ultrasensitive for imaging neuronal activity with custom wide field optical microscope to analyze a large number of individual neurons in living brains. Wide-field microscopy provides a large field of view and better spatial resolution approaching the Abbe diffraction limit of fluorescent microscope. To demonstrate the advantages of this optical platform, we imaged a deep brain structure, the Hippocampus, and tracked hundreds of neurons over time while mouse was performing a memory task to investigate how those individual neurons related to behavior. In addition, we tested our optical platform in investigating transient neural network changes upon mechanical perturbation related to blast injuries. In this experiment, all blasted mice show a consistent change in neural network. A small portion of neurons showed a sustained calcium increase for an extended period of time, whereas the majority lost their activities. Finally, using optogenetic silencer to control selective motor cortex neurons, we examined their contributions to the network pathology of basal ganglia related to Parkinson’s disease. We found that inhibition of motor cortex does not alter exaggerated beta oscillations in the striatum that are associated with parkinsonianism. Together, these results demonstrate the potential of developing integrated optogenetic system to advance our understanding of the principles underlying neural network computation, which would have broad applications from advancing artificial intelligence to disease diagnosis and treatment.

The selective deployment of attention over time optimises our perception and action at the moments when relevant events are expected to happen. Such "temporal orienting" to moments when something is going to happen is especially useful when this information can be combined with predictions about where and what events are likely to occur. A large body of research has already established how temporal predictions dynamically influence our perception and action, but questions remain regarding the neural bases of these attentional mechanisms. In this thesis I present three magnetoencephalography (MEG) studies that I conducted to investigate anticipatory neural dynamics associated with spatial-temporal orienting of attention for perception and action. I also investigate and discuss how such anticipatory dynamics change with ageing and neurodegeneration in Parkinson's disease (PD), and how these anticipatory neural dynamics behave in situations where a complex, hidden spatial-temporal structure is present. In Chapter 1, I introduce the topic of this thesis by reviewing the literature on temporal orienting of attention and by introducing my specific research questions. In Chapter 2, I present an MEG study on anticipatory neural dynamics of joint spatial-temporal orienting of attention in the visual domain, in younger and older adults. This study shows that neural dynamics with spatial, temporal and spatial-temporal orienting are all differentially affected by ageing. In Chapter 3, I describe an MEG experiment that investigates anticipatory neural dynamics during spatial-temporal motor preparation and compares PD participants to healthy control participants. This study reveals that both behavioural and neural dynamics with temporal orienting are affected in PD. In Chapter 4, I describe an experiment that explores how an implicit spatial-temporal structure is utilised to predict and prepare for upcoming actions. This study shows that motor cortical excitability is dynamically modulated in anticipation of the location and timing of events, even when such expectations are hidden in complex visual-motor sequences that remain largely implicit. In Chapter 5, the General discussion, I place these results in their wider context and discuss limitations and future directions.

Apathy or lack of motivation is increasingly recognized to be a major factor affecting quality of life and prognosis in many neurological conditions. It is particularly prevalent in Parkinson's disease, impacting on every disease stage, including de novo cases, and has been reported to affect up to 70% of cases. Despite the pervasiveness of apathy, challenges remain in its detection, clinical assessment and treatment. Several lines of evidence have implicated fronto-striatal reward related neural pathways in the genesis of apathy but the precise processes remain to be fully explained. This thesis examines the potential mechanisms of apathy using Parkinson's disease as a model to study the condition. Novel oculomotor tasks that used eye movement and pupillary responses were developed to help assess if insensitivity to incentives could be an underlying component of apathy. This was examined in healthy young and elderly participants as well as in patients with Parkinson's disease. Patients were tested both ON and OFF their normal dopaminergic medication so that the effect of dopamine could be assessed and the association with apathy determined. This was also performed in a pharmacological study in young participants with the use of Haloperidol, a dopaminergic D2-selective antagonist. Insensitivity to rewards modulated by dopamine was regarded to be a contributory mechanism of apathy in Parkinson's disease and also applicable to general mechanisms of motivation in healthy populations.

Les ganglions de la base (GB) sont des structures cérébrales profondes participant à la sélection de comportements adaptés, avec ses composantes motrices, cognitives et émotionnelles. L’étude par IRMf BOLD de ces structures présente un grand intérêt pour explorer leur rôle et leur dysfonctionnement dans certaines pathologies, comme la maladie de Parkinson (MP). Cette technique permet, par l’étude du signal BOLD, de mettre en évidence des activations cérébrales suite à une activation neuronale. Or l’IRMf BOLD a été optimisée pour l’étude des activations corticales, et la mise en évidence d’activations dans les GB est difficile, surtout au niveau individuel. Ceci est en parti lié au fait que le signal BOLD est plus faible dans ces structures par rapport au cortex. Plusieurs raisons peuvent expliquer ce faible signal BOLD. Ainsi la charge en fer de ses structures, modifiant le paramètre de relaxation T 2 *, peut en être une des causes. En effet, la sensibilité de mesure du signal BOLD est optimale lorsque le temps d’écho (TE) de la séquence d’acquisition égale le T 2 * de la structure cérébrale d’intérêt. Notre premier travail a consisté à étudier l’hétérogénéité du T 2 * dans différentes structures cérébrales en tenant compte des effets de la MP, pathologie connue pour entrainer des accumulations de fer dans certaines régions. Nous avons par ailleurs étudié l’évolution du T 2 * de manière longitudinale, et ce paramètre est apparu comme un biomarqueur intéressant de l’évolutivité de la MP. Le deuxième travail a été consacré à étudier les activations des GB en tenant compte de l’hétérogénéité du T 2 *. Nous avons étudié les activations cérébrales suite à la réalisation d’une tâche motrice, en explorant entre autres l’effet TE. Nous avons montré que le choix du TE a finalement peu d’impact sur la capacité de détection des activations au niveau des GB. Nous proposons une stratégie pour l’étude individuelle de l’activité cérébrale au niveau des GB en utilisant le pourcentage de changement du signal BOLD dans des régions cérébrales d’intérêt préalablement définies sur l’analyse de groupe. / The basal ganglia (BG) are deep brain structures involved in the selection of appropriate behavior, with motor, cognitive and emotional components. The BOLD fMRI study of these structures is of great interest to explore their role and dysfunction in certain diseases, such as Parkinson's disease (PD). By studying the BOLD signal, this technique allows to identify brain activation following neuronal activation. However BOLD fMRI has been optimized for the study of cortical activations and detection of activations in the BG is difficult, mainly at the individual level. This is partly due to the fact that the BOLD signal is lower in these structures in relation to the cortex. Several reasons may explain the BOLD signal attenuation. Thereby, iron load in its structures, which changes the relaxation parameter T 2 *, may be a cause. Indeed, the BOLD signal is optimal when the echo time (TE) of the MRI acquisition sequence equal T 2 * of the considered brain structure. Our first work was to study the heterogeneity of T 2 * in different brain structures, taking into account the effects of PD. Indeed, PD is known to induce iron accumulation some regions. We also studied the evolution of T 2 * longitudinally, and this parameter has emerged as an interesting biomarker to track PD progression. The second work was to study the activation of BG taking into account T 2 * heterogeneity. We studied brain activation during a motor task, exploring in particular the effect of TE. We showed that the choice of TE has a low impact on BG activation detection sensitivity. We propose a strategy for individual quantification of neuronal activity in the BG, using the BOLD percentage signal change in pre-defined regions of interest, obtained from the group analysis.

Introdução: A Doença de Parkinson (DP) é uma desordem neurodegenerativa, progressiva, patologicamente caracterizada pela perda neuronal de dopamina na via nigro-estriatal e pela presença de inclusões intraneuronais de corpos de Lewy. De etiologia desconhecida é consensualmente aceita como uma doença multifatorial com determinantes genéticos, ambientais e relacionados ao envelhecimento. Constitui-se na segunda doença neurodegenerativa mais comum em idosos. Caracteriza-se clinicamente pela tríade tremor, rigidez e bradicinesia. Juntam-se a esses sinais clássicos as alterações posturais, que levam a DP a ser considerada fator de risco independente para quedas. Apesar disso, a avaliação da estabilidade postural na DP ainda permanece imprecisa e com tratamento difícil. Objetivos e métodos: O principal foco desta dissertação é a compreensão dos mecanismos envolvidos nas alterações do equilíbrio na DP. Neste sentido realizamos uma avaliação da atividade elétrica muscular através da Eletromiografia (EMG) de superfície durante a realização do Pull Test (PT), em português teste de retropulsão. Padrões de latência e amplitude de ativação dos músculos tibial anterior, gastrocnêmio e bíceps femoral foram comparados durante a realização do PT entre pacientes com DP e indivíduos hígidos. Os padrões neurofisiológicos dos pacientes com DP foram comparados com escores no PT, tendência a quedas e administração de levodopa (períodos on e off). Resultados e conclusões: Foram encontradas diferenças significantes na atividade muscular entre DP e controles durante PT. Pacientes com DP apresentaram uma menor latência de ativação muscular. Além disso, após uma repetição em sequência de 10 PT, indivíduos controles apresentaram aumento progressivo das latências, sugerindo habituação. Já os pacientes com DP mantiveram uma latência de ativação constante, ou seja não apresentaram habituação. Não foram observadas diferenças relevantes de atividade muscular entre os DPs com PT positivo e negativo, entre caidores e não caidores e após a ingestão de Levodopa o que sugere a interferência de outros fatores relacionados à estabilidade postural, que levam a quedas na DP, em virtude da natureza heterogênea desses eventos. / Background: Parkinson's disease (PD) is a neurodegenerative disorder, progressive, pathologically characterized by neuronal loss of dopamine in the nigrostriatal pathway and the presence of intraneuronal inclusions of Lewy bodies. Of unknown etiology is widely accepted as a multifactorial disease with genetical, environmental and aging determinants. It constitutes the second most common neurodegenerative disease in the elderly. It is clinically characterized by a triad of tremor, rigidity and bradykinesia. Besides these classic signs we can add postural changes, leading PD to be considered an independent risk factor to falls. Despite this, the assessment of postural stability in PD remains unclear and difficult to treat. Objective and Methods: The main focus of this dissertation is understanding the mechanisms involved in balance disorders in PD. We undertook an assessment of muscle electrical activity through surface electromyography (EMG) while performing a Pull Test (PT). Patterns of latency and amplitude of muscle activation of the tibialis anterior, gastrocnemius and biceps femoris muscles were compared during the course of PT between PD patients and healthy individuals. Neurophysiological patterns of PD patients were compared with scores on the PT, the tendency to fall and administration of levodopa (on and off periods). Results and Conclusion: Significant differences were found in muscle activity between PD and controls during PT. PD patients had a lower latency of muscle activation. Furthermore, after a repetition in sequence of 10 PT, control subjects showed a progressive increase in latency, suggesting habituation. Patients with PD a latency of activation remained constant or showed no habituation. However, there were no significant differences in muscle activity between the PDs with positive and negative PT, between fallers and non fallers and after administration of L-dopa suggesting the influence of other factors related to postural stability, leading to falls in PD, due to the heterogeneous nature of these events.

Base teórica: Os principais sintomas motores da doença de Parkinson, rigidez, bradicinesia e tremor com a progressão da doença, frequentemente são acompanhados por alteração da deglutição que compromete consideravelmente a alimentação dos indivíduos com a doença. A alteração de deglutição está presente na fase oral, faríngea e esofágica e traz consequências para o individuo com doença de Parkinson, como desnutrição, risco de aspiração pulmonar e pneumonia. Apesar da doença de Parkinson (DP) ser primariamente considerada um distúrbio do movimento, algumas características não-motoras são típicas da doença, como alterações cognitivas, distúrbios do sono e distúrbios sensoriais. Objetivo: Estudar a correlação entre as alterações cognitivas e as alterações de deglutição dos indivíduos com DP. Métodos: Trata-se de estudo do tipo transversal e descritivo. O estudo conta com dois grupos: grupo controle, formado por indivíduos saudáveis, (n=47) e grupo de estudo formado por indivíduos com DP (n=47). Para avaliação cognitiva, foi utilizada uma bateria de testes cognitivos, onde foram avaliadas funções como atenção, memória, planejamento, funções executivas, entre outras. Para avaliação de deglutição, foi utilizada avaliação clínica, com base em protocolo, sendo possível avaliar estruturas e a função da deglutição, a fim de classificar o grau de alteração. Resultados: Dos pacientes com DP, 56 % eram do sexo masculino com média de idade de 62,0 (±11,0), escolaridade de 7,0 (±4,0), tempo de diagnóstico de 10,0 (±5,0), Hoehn e Yahr 2 (55%) e Hoehn e Yahr 3 (45%). Para o grupo controle, 56% do sexo masculino com média de idade de 64,0 (±7,0) e escolaridade de 9,0 (±4,0). Na avaliação miofuncional da deglutição entre grupo de estudo e grupo controle, foram observadas diferenças significativas como: face assimétrica p=(0,00), bochechas assimétricas p=(0,00), hipotonia do lado esquerdo p=(0,00), alteração do mentual (p=0,00), hipotonia de língua p=(0,00), tosse p=0,03), engasgos (p=0,00), projeção de língua (p=0,00), projeção de cabeça p=(0,00), resíduos alimentares (p=0,00), contração o periorbicular (p=0,00), deglutição normal (p=0,00), disfagia leve (p=0,04), disfagia leve a moderada (p=0,02). Na comparação do desempenho cognitivo entre os grupos, observou-se significância estatística nos testes de fluência verbal categórico (p=0,00), Rey Verbal A (p=0,00), Rey verbal I (p=0,00), Rey Verbal R (p=0,00). Para a associação entre cognição e deglutição em indivíduos com doença de Parkinson, observou-se o resultado significativo entre Rey Verbal I e deglutição normal (p= 0,02). Conclusão: Os pacientes com DP possuem maiores alterações cognitivas e de deglutição comparados ao grupo controle e o estudo apontou a influência da memória imediata de curto prazo na deglutição, tendo participação importante no processo de deglutição. Também foi possível observar a correlação da idade, H&Y e tempo de evolução da doença na deglutição. / Background: The primary motor symptoms of Parkinson's disease rigidity, bradykinesia and tremor with the progression of the disease are often accompanied by swallowing disorders which greatly compromises the power of individuals with the disease. Swallowing change is present in the oral, pharyngeal and esophageal and has consequences for the individual with Parkinson's disease, such as malnutrition, pulmonary aspiration and pneumonia. Although Parkinson's disease (PD) is primarily regarded as a disorder of movement, some non-motor characteristics are typical of the disease, and cognitive changes, sleep disorders and sensory disturbances. Objective: To study the correlation between cognitive impairment and swallowing disorders among individuals with PD. Objective: To study the correlation between cognitive impairment and swallowing disorders among individuals with PD. Methods: This is a study of cross-sectional and descriptive. The study has two groups: control group, consisting of healthy subjects (n= 47) and study group of individuals diagnosed with Parkinson's disease (n= 47). For cognitive evaluation, we used a battery of cognitive tests, which were evaluated functions such as attention, memory, planning, executive functions, among others. For evaluation of swallowing, clinical evaluation was used, based on protocol so it can evaluate structures and the function of swallowing in order to classify the degree of change. Results: Of PD patients, 56% were male with a mean age of 62.0 (±11.0), educational level of 7.0 (±4.0), diagnosis time of 10.0 (±5.0), Hoehn and Yahr 2 (55%) and Hoehn and Yahr 3 (45%). For the control group, 56% were male with a mean age of 64.0 (±7.0) and schooling of 9.0 (±4.0). In myofunctional evaluation of swallowing between study and control groups was observed significant differences as asymmetric face (p=0.00), asymmetrical cheeks (p=0.00), hypotonia the left (p=0.00), alteration of the mental (p=0.00), speaking hypotonia (p=0.00), cough (p=0.03), choking (p=0.00), tongue projection (p=0.00), head projection (p=0.00), food waste (p=0.00), the contraction periorbicular (p=0.00), normal swallowing (p=0.00), light dysphagia (p=0.04), mild to moderate dysphagia (p=0.02). In comparing cognitive performance between the groups there was statistical significance in categorical verbal fluency tests (p=0.00), Rey Verbal A (p=0.00), verbal Rey I (p=0.00), Rey verbal R (p=0.00). For the association between cognition and swallowing in people with Parkinson's disease was observed between the mean result Rey Verbal I and normal swallowing (p =0.02). The study also showed the influence of gender, age, disease stage and time of diagnosis in cognitive performance and swallowing. Conclusion: PD patients have higher cognitive and swallowing changes compared to the control group and the study pointed out the influence of short-term immediate memory in swallowing, with important participation in the swallowing process. It was also possible to observe the correlation of age, H & Y and duration of the disease in swallowing.

Title: The influence of the dance movement therapy on psychomotor symptoms of Parkinson's disease patients Objectives: The aim of this thesis is to evaluate the effects of dance movement therapy on postural instability and other motor and non-motor symptomatology of patients with Parkinson's disease. Changes are evaluated by using MDS-UPDRS and Computerized Dynamic Posturography (NeuroCom Smart EquiTest System). Another goal is to provide comprehensive information about dance movement therapy and other dance therapies promoted abroad and to highlight a possibility of their use as a non-pharmacological treatment of Parkinson's disease symptoms. Methods: This pilot study involved eight late onset Parkinson's disease patients at an average age of 68,87±6,69 years. Changes in their postural stability and motor and non-motor symptoms of Parkinson's disease were evaluated after the completion of two months of intensive dance movement therapy. Observed parameters were evaluated by using MDS- UPDRS and the Computerized Dynamic Posturography Smart EquiTest System created by the NeuroCom company, before and after the therapeutic programme. For effective assessment of the therapy, statistical methods (the Student's paired t-test and the Wilcoxon rank sum test) were used along with the rate of clinical...

Este trabalho teve como objetivo investigar as funções executivas (FE) e alterações do humor em pacientes com doença de Parkinson (DP). O primeiro estudo procurou apresentar uma revisão sistemática da literatura sobre o tema. No artigo seguinte, em um estudo empírico, comparou-se o desempenho das FE e alterações do humor em um grupo de pacientes com DP (N= 40) e um grupo controle (N= 30). O grupo clínico apresentou desempenho significativamente inferior em diversas medidas de avaliação cognitiva, especialmente no instrumento Behavioural Assessment of the Dysexecutive Syndrome (BADS), mas não para as variáveis ansiedade e depressão (p< 0,05). Os resultados demonstram que as alterações das FE e depressão são transtornos frequentes, mesmo em fases iniciais da DP. / This work aimed to investigate the executive functions (EF) and mood changes in patients with Parkinson's disease (PD). The first study sought to present a systematic review of the literature on the subject. In the second, in an empirical study, we compared the performance in EF and mood in a group of PD patients (N = 40) and a control group (N = 30). The clinical group had a significantly poorer performance on several measures of cognitive assessment, especially the BADS, but not for the variables anxiety and depression (p <0.05). The results show that changes in EF are frequent disorders, even in early stages of PD.