925 resultados para Non-motor symptom


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Parkinson’s disease is a chronic progressive neurodegenerative disorder characterized by the selective loss of dopaminergic neurons in the SNpc resulting in severe motor impairments. Serotonergic system plays an important regulatory role in the pathophysiology of PD in rats, the evaluation of which provides valuable insight on the underlying mechanisms of motor, cognitive and memory deficits in PD. We observed a decrease in 5-HT content in the brain regions of 6-OHDA infused rat compared to control. The decreased 5-HT content resulted in a decrease of total 5-HT, 5-HT2A receptors and 5-HTT function and an increase of 5-HT2C receptor function. 5-HT receptor subtypes - 5-HT2A and 5-HT2C receptors have differential regulatory role on the modulation of DA neurotransmission in different brain regions during PD. Our observation of impaired serotonergic neurotransmission in SNpc, corpus striatum, cerebral cortex, hippocampus, cerebellum and brain stem demonstrate that although PD primarily results from neurodegeneration in the SNpc, the associated neurochemical changes in other areas of the brain significantly contributes to the different motor and non motor symptoms of PD. The antioxidant enzymes – SOD, CAT and GPx showed significant down regulation which indicates increased oxidative damage resulting in neurodegeneration. We also observed an increase in the level of lipid peroxidation. Reduced expression of anti-apoptotic Akt and enhanced expression of NF-B resulting from oxidative stress caused an activation of caspase-8 thus leading the cells to neurodegeneration by apoptosis. BMC administration in combination with 5-HT and GABA to PD rats showed reversal of the impaired serotonergic neurotransmission and oxidative stress mediated apoptosis. The transplanted BMC expressed NeuN confirming that 5-HT and GABA induced the differentiation and proliferation of BMC to neurons in the SNpc along with an increase in DA content and an enhanced expression of TH. Neurotrophic factors – BDNF and GDNF rendered neuroprotective effects accompanied by improvement in behavioural deficits indicating a significant reversal of altered dopaminergic and serotonergic neurotransmission in PD. The restorative and neuroprotective effects of BMC in combination with 5-HT and GABA are of immense therapeutic significance in the clinical management of PD.

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Visuospatial attentional bias was examined in Huntington's disease (HID) patients with mild disease, asymptomatic gene-positive patients and controls. No group differences were found on the grey scales task (which is a non-motor task of visuospatial attentional bias), although patients' trinucleotide (CAG) repeat length correlated with increasing leftward bias. On the line bisection task, symptomatic patients made significantly larger leftward bisection errors relative to controls, who showed the normal slight degree of leftward error (pseudo-neglect). The asymptomatic group showed a trend for greater leftward error than controls. A subset of participants went on to have structural MRI, which showed a correlation between increased leftward error on the line bisection task and reduced density in the angular gyrus area (BA39) bilaterally. This finding is consistent with recent literature suggesting a critical role for the angular gyrus in the lateralization of visuospatial attention.

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Background: Impairment in non-motor functions such as disturbances of some executive functions are also common events in Parkinson's disease patients. Objective: To verify the performance of Parkinson's disease patients in activities requiring visuoconstructive and visuospatial skills. Method: Thirty elderly patients with mild or moderate stages of Parkinson's disease were studied. The assessment of the clinical condition was based on the unified Parkinson's disease rating scale (56.28; SD=33.48), Hoehn and Yahr (2.2; SD=0.83), Schwab and England (78.93%), clock drawing test (7.36; SD=2.51), and mini-mental state examination (26.48; SD=10.11). Pearson's correlation and stepwise multiple regression were used for statistical analyses. Results: The patients presented deterioration in visuospatial and visuoconstructive skills. Conclusion: The clock drawing test proved to be a useful predictive tool for identifying early cognitive impairment in these individuals.

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A doença de Parkinson (DP) é a segunda doença neurodegenerativa mais comum em idosos, caracterizada pela neurodegeneração de neurônios dopaminérgicos da substância negra (SN), com etiologia não claramente estabelecida, entretanto as causas podem estar associadas a exposição de toxinas ambientais e fatores genéticos. Os processos patológicos envolvidos na DP são disfunção mitocondrial, estresse oxidativo, inflamação e excitotoxicidade. A sintomatologia da DP são alterações motoras, cognitivas e autonômicas. Contudo, poucos estudos analisam os sintomas não-motores da DP, principalmente em modelos animais. Nesse contexto o objetivo deste trabalho foi avaliar sintomas não-motores da DP em modelo animal com lesão provocada pela neurotoxina 6-hidroxidopamina com duas doses diferentes, injetadas bilateralmente no estriado. Para alcançar nossos objetivos realizamos os testes de campo aberto, apomorfina, labirinto aquático de Morris e testes de discriminação olfativa, além de análises histológicas. Nossos resultados mostraram alterações motoras, déficits de memória e aprendizado, associadas a diminuição de células dopaminérgicas na SN, neurônios estriatais e neurônios da região hipocampal CA1. Dessa forma, esse modelo para os sintomas não-motores da DP pode ser utilizado para a compreensão dos mecanismos que envolvem a doença, assim como para avaliar medidas terapêuticas que possam retardar ou interromper a progressão da DP.

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The purpose of this study was to analyze the effect of different exercise programs on the psychological and cognitive functions in patients with Parkinson's disease (PD). Forty-five patients with PD participated in the study. The participants were randomized in three intervention programs: Group-1 (n=15, cognitive-activities), Group-2 (n=15, multimodal exercise) and Group-3 (n=15, exercises for posture and gait). The clinical, psychological and cognitive functions were assessed before and after 4 months of intervention. Univariate analysis did not reveal significant interactions between groups and time (p>0.05). However, univariate analysis for time revealed differences in stress level and memory. Participants showed less physical stress (p<0.01) and overall stress (p < 0.04) and higher performance in episodic declarative memory (p < 0.001) after exercise. These findings suggest that group work with motor or non-motor activities can improve cognitive and psychological functions of patients with PD.

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Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

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Der Erfolg einer Schizophrenie-Behandlung ist zum größten Teil abhängig vom Ansprechen des Patienten auf seine antipsychotische Medikation. Welches Medikament und welche Dosis bei einem individuellen Patienten wirksam sind, kann derzeit erst nach mehrwöchiger Behandlung beurteilt werden. Ein Grund für variierendes Therapieansprechen sind variable Plasmakonzentrationen der Antipsychotika. Ziel dieser Arbeit war es, zu untersuchen, in wieweit der Therapieerfolg zu einem frühen Zeitpunkt der Behandlung durch objektive Symptomerfassung vorhersagbar ist und welche Faktoren die hohe Variabilität der Antipsychotikaspiegel im Blut beeinflussen. rnEine 18-monatige naturalistische klinische Studie an schizophrenen Patienten wurde durchgeführt, um folgende Fragen zu beantworten: Kann man das Therapieansprechen prädizieren und welche Instrumente sind dafür geeignet? Die Psychopathologie wurde anhand zweier Messskalen (Brief Psychiatric Rating Scale, BPRS und Clinical Global Impressions, CGI) wöchentlich ermittelt, um die Besserung der Krankheitssymptome im Verlauf von 8 Wochen zu bewerten. Therapiebegleitend wurden noch die Serum-Konzentrationen der Antipsychotika gemessen. Objektive Symptomerfassung durch BPRS oder CGI waren als Messinstrumente geeignet, Therapieansprechen vorherzusagen. Bezogen auf den Behandlungsbeginn war eine Verminderung der Symptome hoch prädiktiv für späteres Therapieversagen oder -ansprechen. Eine Verminderung um mehr als 36,5% auf der BPRS Skala in Woche 2 wurde als signifikanter Schwellenwert für Nichtansprechen ermittelt. Patienten, deren Symptombesserung unterhalb des Schwellenwertes lag, hatten eine 11,2-fach höhere Wahrscheinlichkeit, am Ende der Studie nicht auf ihre medikamentöse Therapie anzusprechen als die Patienten, die sich um mindestens 36,5% verbesserten. Andere Faktoren, wie Alter, Geschlecht, Dauer der Erkrankung oder Anzahl der stationären Aufenthalte hatten keinen Einfluss auf die Prädiktion des Therapieansprechens. Therapeutische Antipsychotika-Spiegel übten einen positiven Einfluss auf die Ansprechrate aus. Bei Patienten mit therapeutischen Spiegeln war das Ansprechen rascher und die Ansprechrate größer als unter denjenigen deren Spiegel außerhalb der therapeutisch üblichen Bereiche lag. rnEine wichtige Voraussetzung für den Einsatz von TDM ist das Vorhandensein einer präzisen, reproduzierbaren, zeit- und kostensparenden analytischen Methode zur quantitativen Bestimmung der untersuchten Substanzen. Die Entwicklung und Validierung einer solchen geeigneten Methode wurde für den Nachweis von Haloperidol vorgenommen. Eine HPLC-Methode mit Säulenschaltung erwies sich für TDM geeignet. rnBasierend auf den Ergebnissen der eigenen klinischen Studie zur Response Prädiktion wurde untersucht, welche Faktoren die Variabilität der Pharmakokinetik von Antipsychotika beeinflussen. Die Variabilität der Pharmakokinetik ist ein Grund für fehlendes oder unzureichendes Ansprechen. Es wurde zum einen der Einfluss der galenischen Formulierung auf die Freisetzung und zum anderen der Einfluss von entzündlichen Prozessen auf die Metabolisierung eines Antipsychotikums untersucht. Dazu wurden Patientendaten retrospektiv ausgewertet.rnDie Analyse von 247 Serumspiegeln von Patienten, die mit Paliperidon in OROS®Formulierung, einer neu eingeführten Retardform, behandelt wurden, zeigte, dass die intraindividuelle Variabilität der Talspiegel (Vk) von Paliperidon 35% betrug. Er war damit vergleichbar wie für nicht retardiertes Risperidon 32% (p=n.s.). Die Retardierung hatte demnach keinen Varianz mindernden Effekt auf die Talspiegel des Antipsychotikums. Der Wirkstoff-Konzentrations-Bereich lag bei 21-55 ng/ml und entsprach ebenfalls nahezu dem therapeutischen Bereich von Risperidon (20-60 ng/ml). rnEntzündliche Prozesse können die Metabolisierung von Medikamenten verändern. Dies wurde bisher für Medikamente nachgewiesen, die über CYP1A2 abgebaut werden. Durch die eigene Analyse von 84 Patienten-Serumspiegeln konnte festgestellt werden, dass die Metabolisierung von Quetiapin während eines entzündlichen Prozesses beeinträchtigt war, wahrscheinlich durch Hemmung von CYP3A4. Dies sprach dafür, dass auch Wirkstoffe, die über CYP3A4 abgebaut werden, während eines entzündlichen Prozesses im Körper in ihrer Pharmakokinetik beeinträchtigt sein können. Aus diesem Grund sollte während einer Infektion unter der Therapie mit Quetiapin besonders auf die Nebenwirkungen geachtet werden und der Serumspiegel sollte in dieser Zeit überwacht werden, um den Patienten vor eventuellen Nebenwirkungen oder sogar Intoxikationen zu schützen. rnDie Befunde dieser Arbeit zeigen, dass bei einer Behandlung schizophrener Patienten mit Antipsychotika die Messung der Psychopathologie zur Vorhersage des Therapieansprechens und die Messung der Blutspiegel zur Identifizierung von Faktoren, die die pharmakokinetische Variabilität bedingen, geeignet sind. Objektive Symptomerfassung und Therapeutisches Drug Monitoring sind demnach Instrumente, die für die Steuerung der antipsychotischen Pharmakotherapie genutzt werden sollten.rn

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Background: cognitive impairment is one of the non motor features widely descripted in parkinsonian syndrome, it has been related to the motor characteristics of the parkinsonian syndrome, associated with neuropsychiatric dysfunction and the characteristic sleep and autonomic features. It has been shown to be highly prevalent at all disease stages and to contribute significantly to disability. Objectives: aim of this study is to evaluate longitudinally the cognitive and behavioral characteristics of patients with a parkinsonian syndrome at onset; to describe the cognitive and behavioral characteristics of each parkinsonian syndrome; to define in PD patients at onset the presence of MCI or Parkinson disease dementia; to correlate the cognitive and behavioral characteristics with the features of the parkinsonian syndrome and with the associated sleep and autonomic features. Results: we recruited 55 patients, 22 did not present cognitive impairment both at T0 and at T1. 18 patients presented a progression of cognitive impairment. Progressive cognitively impaired patients were older and presented the worst motor phenotype. Progression of cognitive impairment was not associated to sleep and autonomic features. Conclusion: the evaluation of cognitive impairment could not be useful as a predictor of a correct diagnosis but each non motor domain will help to clarify and characterize the motor syndrome. The diagnosis of parkinsonian disorders lies in building a clinical profile in conjunction with other clinical characteristics such as mode of presentation, disease progression, response to medications, sleep and autonomic features.

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DJ-1 is mutated in autosomal recessive, early onset Parkinson's disease but the exact localization of the DJ-1 gene product in the mammalian brain is largely unknown. We aimed to evaluate the DJ-1 mRNA expression pattern in the mouse brain. Serial coronal sections of brains of five male and five female adult mice were investigated by using in situ hybridization with a DJ-1 specific 35S-labeled oligonucleotide probe. Hybridized sections were analyzed after exposure to autoradiography films and after coating with a photographic emulsion. DJ-1 was heterogeneously expressed throughout the mouse central nervous system. A high expression of DJ-1 mRNA was detected in neuronal and non-neuronal populations of several structures of the motor system such as the substantia nigra, the red nucleus, the caudate putamen, the globus pallidus, and the deep nuclei of the cerebellum. Furthermore, DJ-1 mRNA was also highly expressed in non-motor structures including the hippocampus, the olfactory bulb, the reticular nucleus of the thalamus, and the piriform cortex. The high expression of DJ-1 mRNA in brain regions involved in motor control is compatible with the occurrence of parkinsonian symptoms after DJ-1 mutations. However, expression in other regions indicates that a dysfunction of DJ-1 may contribute to additional clinical features in patients with a DJ-1 mutation.

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As a more complete picture of the clinical phenotype of Parkinson's disease emerges, non-motor symptoms have become increasingly studied. Prominent among these non-motor phenomena are mood disturbance, cognitive decline and dementia, sleep disorders, hyposmia and autonomic failure. In addition, visual symptoms are common, ranging from complaints of dry eyes and reading difficulties, through to perceptual disturbances (feelings of presence and passage) and complex visual hallucinations. Such visual symptoms are a considerable cause of morbidity in Parkinson's disease and, with respect to visual hallucinations, are an important predictor of cognitive decline as well as institutional care and mortality. Evidence exists of visual dysfunction at several levels of the visual pathway in Parkinson's disease. This includes psychophysical, electrophysiological and morphological evidence of disruption of retinal structure and function, in addition to disorders of ‘higher’ (cortical) visual processing. In this review, we will draw together work from animal and human studies in an attempt to provide an insight into how Parkinson's disease affects the retina and how these changes might contribute to the visual symptoms experienced by patients.

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The importance of the cerebellum for non‐motor functions is becoming more and more evident. The influence on cognitive functions from acquired cerebellar lesions during childhood, however, is not well known. We present follow‐up data from 24 patients, who were operated upon during childhood for benign cerebellar tumours. The benign histology of these tumours required neither radiotherapy nor chemotherapy. Post‐operatively, these children were of normal intelligence with a mean IQ of 99.1, performance intelligence quotient (PIQ) of 101.3 and verbal intelligence quotient (VIQ) of 96.8. However, 57% of patients showed abnormalities in subtesting. In addition, more extensive neuropsychological testing revealed significant problems for attention, memory, processing speed and interference. Visuo‐constructive problems were marked for copying the Rey figure, but less pronounced for recall of the figure. Verbal fluency was more affected than design fluency. Behavioural deficits could be detected in 33% of patients. Attention deficit problems were marked in 12.5%, whereas others demonstrated psychiatric symptoms such as mutism, addiction problems, anorexia, uncontrolled temper tantrums and phobia. Age at tumour operation and size of tumour had no influence on outcome. Vermis involvement was related to an increase in neuropsychological and psychiatric problems. The observation that patients with left‐sided cerebellar tumours were more affected than patients with right‐sided tumours is probably also influenced by a more pronounced vermian involvement in the former group. In summary, this study confirms the importance of the cerebellum for cognitive development and points to the necessity of careful follow‐up for these children to provide them with the necessary help to achieve full integration into professional life.

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The "Ardouin Scale of Behavior in Parkinson's Disease" is a new instrument specifically designed for assessing mood and behavior with a view to quantifying changes related to Parkinson's disease, to dopaminergic medication, and to non-motor fluctuations. This study was aimed at analyzing the psychometric attributes of this scale in patients with Parkinson's disease without dementia. In addition to this scale, the following measures were applied: the Unified Parkinson's Disease Rating Scale, the Montgomery and Asberg Depression Rating Scale, the Lille Apathy Rating Scale, the Bech and Rafaelsen Mania Scale, the Positive and Negative Syndrome Scale, the MacElroy Criteria, the Patrick Carnes criteria, the Hospital Anxiety and Depression Scale, and the Mini-International Neuropsychiatric Interview. Patients (n = 260) were recruited at 13 centers across four countries (France, Spain, United Kingdom, and United States). Cronbach's alpha coefficient for domains ranged from 0.69 to 0.78. Regarding test-retest reliability, the kappa coefficient for items was higher than 0.4. For inter-rater reliability, the kappa values were 0.29 to 0.81. Furthermore, most of the items from the Ardouin Scale of Behavior in Parkinson's Disease correlated with the corresponding items of the other scales, depressed mood with the Montgomery and Asberg Depression Rating Scale (ρ = 0.82); anxiety with the Hospital Anxiety and Depression Scale-anxiety (ρ = 0.56); apathy with the Lille Apathy Rating Scale (ρ = 0.60). The Ardouin Scale of Behavior in Parkinson's disease is an acceptable, reproducible, valid, and precise assessment for evaluating changes in behavior in patients with Parkinson's disease without dementia. © 2015 International Parkinson and Movement Disorder Society.

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n recent years, the development of advanced driver assistance systems (ADAS) – mainly based on lidar and cameras – has considerably improved the safety of driving in urban environments. These systems provide warning signals for the driver in the case that any unexpected traffic circumstance is detected. The next step is to develop systems capable not only of warning the driver but also of taking over control of the car to avoid a potential collision. In the present communication, a system capable of autonomously avoiding collisions in traffic jam situations is presented. First, a perception system was developed for urban situations—in which not only vehicles have to be considered, but also pedestrians and other non-motor-vehicles (NMV). It comprises a differential global positioning system (DGPS) and wireless communication for vehicle detection, and an ultrasound sensor for NMV detection. Then, the vehicle's actuators – brake and throttle pedals – were modified to permit autonomous control. Finally, a fuzzy logic controller was implemented capable of analyzing the information provided by the perception system and of sending control commands to the vehicle's actuators so as to avoid accidents. The feasibility of the integrated system was tested by mounting it in a commercial vehicle, with the results being encouraging.

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A fadiga é um sintoma inespecífico, encontrado com freqüência na população. Ela é definida como sensação de cansaço físico profundo, perda de energia ou mesmo sensação de exaustão, e é importante a sua diferenciação com depressão ou fraqueza. Os transtornos depressivos e ansiosos constituem os transtornos psiquiátricos mais freqüentes no idoso, e quase sempre dão lugar a conseqüências graves neste grupo etário. Este estudo visa avaliar a influência da ansiedade e depressão sobre o desencadeamento de fadiga e evolução de problemas de saúde e de comportamentos peculiares ao processo de envelhecimento. Trata-se de um estudo, do tipo caso-controle investigando ansiedade, depressão e fadiga. Foram avaliados 61 indivíduos com 60 anos de idade ou mais. Um grupo controle constituído por 60 indivíduos jovens (idade até 35 anos), foram selecionados entre estudantes do Centro Universitário de Santo André que responderam um Questionário de Características Gerais, um Inventário de Ansiedade traço-estado, um Inventário de Depressão de Beck e uma Escala de Severidade de Fadiga. O grupo de idosos apresentou um escore significativamente maior em relação ao grupo controle na escala de severidade de fadiga. O grupo de idosos apresentou escore médio de 36,87 ± 14,61 enquanto o grupo controle apresentou escore médio de 31,47 ± 12,74 (t = 2,167; df = 119; p = 0,032). No entanto, o grupo de idosos apresentou escores significativamente maiores na escala de Beck (10,54 ± 8,63) em relação aos controles (6,83 ± 7,95); t = 2,455; df = 119; p = 0,016). Analisando-se apenas o grupo de indivíduos idosos, observou-se uma correlação significativa entre os escore da escala de severidade de fadiga e a escala de depressão de Beck (correlação de Pearson = 0,332; p = 0,009). Ainda trabalhando apenas com o grupo de indivíduos idosos, observou-se um escore significativamente maior da escala de severidade de fadiga naqueles indivíduos que praticavam atividade física regular, sendo, escore médio de 31,55 ± 13,36; (t = 2,203; df = 58; p = 0,032). A partir da análise dos resultados deste estudo pôde-se concluir que o grupo de indivíduos idosos apresentam estatisticamente significante escore maior, quando comparado com o grupo controle, apresentando mais sintomas de fadiga e depressão. Estes sintomas de fadiga ocorreram em conjunto com sintomas depressivos sugerindo uma possível correlação entre estes. Quando se observou apenas os idosos, esta correlação foi confirmada. Analisado-se ainda somente o grupo de indivíduos idosos observa-se que o grupo de idosos que praticam atividade física regularmente apresentam menos sintomas fadiga que o grupo que não pratica atividade física.(AU)

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A fadiga é um sintoma inespecífico, encontrado com freqüência na população. Ela é definida como sensação de cansaço físico profundo, perda de energia ou mesmo sensação de exaustão, e é importante a sua diferenciação com depressão ou fraqueza. Os transtornos depressivos e ansiosos constituem os transtornos psiquiátricos mais freqüentes no idoso, e quase sempre dão lugar a conseqüências graves neste grupo etário. Este estudo visa avaliar a influência da ansiedade e depressão sobre o desencadeamento de fadiga e evolução de problemas de saúde e de comportamentos peculiares ao processo de envelhecimento. Trata-se de um estudo, do tipo caso-controle investigando ansiedade, depressão e fadiga. Foram avaliados 61 indivíduos com 60 anos de idade ou mais. Um grupo controle constituído por 60 indivíduos jovens (idade até 35 anos), foram selecionados entre estudantes do Centro Universitário de Santo André que responderam um Questionário de Características Gerais, um Inventário de Ansiedade traço-estado, um Inventário de Depressão de Beck e uma Escala de Severidade de Fadiga. O grupo de idosos apresentou um escore significativamente maior em relação ao grupo controle na escala de severidade de fadiga. O grupo de idosos apresentou escore médio de 36,87 ± 14,61 enquanto o grupo controle apresentou escore médio de 31,47 ± 12,74 (t = 2,167; df = 119; p = 0,032). No entanto, o grupo de idosos apresentou escores significativamente maiores na escala de Beck (10,54 ± 8,63) em relação aos controles (6,83 ± 7,95); t = 2,455; df = 119; p = 0,016). Analisando-se apenas o grupo de indivíduos idosos, observou-se uma correlação significativa entre os escore da escala de severidade de fadiga e a escala de depressão de Beck (correlação de Pearson = 0,332; p = 0,009). Ainda trabalhando apenas com o grupo de indivíduos idosos, observou-se um escore significativamente maior da escala de severidade de fadiga naqueles indivíduos que praticavam atividade física regular, sendo, escore médio de 31,55 ± 13,36; (t = 2,203; df = 58; p = 0,032). A partir da análise dos resultados deste estudo pôde-se concluir que o grupo de indivíduos idosos apresentam estatisticamente significante escore maior, quando comparado com o grupo controle, apresentando mais sintomas de fadiga e depressão. Estes sintomas de fadiga ocorreram em conjunto com sintomas depressivos sugerindo uma possível correlação entre estes. Quando se observou apenas os idosos, esta correlação foi confirmada. Analisado-se ainda somente o grupo de indivíduos idosos observa-se que o grupo de idosos que praticam atividade física regularmente apresentam menos sintomas fadiga que o grupo que não pratica atividade física.(AU)