Navegando por Palavras-chave "alzheimer"

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    Avaliação da capacidade citoprotetora dos novos análogos da tacrina em linhagem estabelecida de astrócitos e células pc-12
    (Universidade Federal de São Paulo (UNIFESP), 2015-10-04) Bastos, Carolina Maria Alves [UNIFESP]; Jurkiewicz, Aron Jurkiewicz [UNIFESP]; Universidade Federal de São Paulo (UNIFESP)
    A tacrina é um potente e reversível inibidor da acetilcolinesterase utilizado para o tratamento da doença de Alzheimer (DA). Porém, como a terapia com a tacrina geralmente resulta em hepatotoxicidade, a pesquisa por novos fármacos derivados desta molécula tem sido encorajada. Como exemplo destes compostos estão as tacpirimidinas IHT 1009 e IHT12127, desenvolvidas a partir da molécula da tacrina. Desta forma, para testar a capacidade citoprotetora destes compostos (tacpirimidinas) frente ao peróxido de hidrogênio (H2O2), dois modelos de células de sistema nervoso central, sendo uma linhagem de astrócitos imortalizada (como modelo glial) e uma linhagem de células PC-12 (como modelo neuronal) foram utilizadas. A tacrina foi utilizada como controle positivo de citoproteção. Para a determinação da citotoxicidade e para a escolha das concentrações e tempos de exposição ao tratamento a serem utilizadas no decorrer deste trabalho, utilizamos o teste de redução do MTT a cristais de formazan. Foram efetuados testes nas duas linhagens celulares, através do período de incubação de 6h, 12h e 24h, com as concentrações de 1,25?M; 2,5?M e 5?M das tacpirimidinas; as concentrações de 2?M; 2,5?M; 3?M; 5?M; 10?M; 20?M e 30?M de tacrina e o H2O2 nas concentrações de 0,5?M; 1?M; 1,25?M; 1,5?M; 2,5?M; 5?M; 10?M; 20?M; 30?M e 40?M; nos períodos de incubação de 30minutos 1h, 3h e 6h. Como resultado, optamos por utilizar as concentrações que não apresentaram toxicidade de 2,5?M das IHT1009 e IHT12127, além da concentração similar de 2,5?M da tacrina para efetuarmos pré-tratamento por 24h das células antes de serem expostas ao agente agressor H2O2, pelo período de incubação de 1h na concentração de 30?M (por ser a concentração capaz de suprimir 50% das células em cultura). No estudo de ciclo celular com PI verificamos nos grupos que receberam apenas pré-tratamento por 24h com a tacrina e com as IHT 1009 e 12127 ausência de diferenças significativas em relação ao grupo controle sem tratamento quando avaliamos o número de células na fase G1/S/G2/M e na fração Sub-G1. Porém o grupo que recebeu o H2O2 por 1h apresentou um aumento significativo de células na porção Sub-G1 do histograma. A morte celular, avaliada por Anexina-FITC/PI demonstrou uma diminuição de morte por apoptose nos astrócitos pré-tratados com tacrina, IHT 1009 e IHT 12127 quando foram previamente desafiados com o H2O2. Quanto a apoptose tardia ou necrose secundaria, verificamos que as tacpirimidinas assim como a tacrina foram capazes de proteger as células gliais do insulto provocado pelo H2O2. Quanto a células PC-12, não obtivemos o mesmo resultado, pois não foi verificada nenhuma capacidade citoprotetora destes compostos na presença do H2O2. Uma diminuição na atividade de caspase-3 apenas nos astrócitos tratados com as IHT´s também foi observada. A atividade das espécies reativas de oxigênio (EROs) através da análise em citometria de fluxo utilizando-se a sonda DCF demonstrou um efeito antioxidante promissor nos grupos de astrócitos pré-tratados com a IHT 1009 e a IHT 12127 na presença do H2O2, com a diminuição da geração de EROs. Por fim avaliamos a capacidade de mobilizar cálcio intracelular da IHTs em comparação com a tacrina. Observamos que nos astrócitos, a IHT 1009 diminuiu a liberação de cálcio intracelular, tal qual a tacrina. Entretanto, na linhagem de células PC12, onde as tacpirimidinas não foram capazes de proteger estas células do insulto causado pelo peróxido, um aumento na liberação de cálcio citoplasmático foi verificado, sugerindo assim que estas respostas diferentes quanto a liberação de cálcio está contribuindo para as respostas distintas quanta a citoproteção observada neste trabalho apenas para os astrócito. Em suma, podemos observar que o estudo comparativo entre a ação das tacpirimidinas em duas linhagens é de grande importância para o entendimento dos mecanismos de defesa do sistema nervoso central frente a um agente agressor. Além disso, a utilização de mais de um tipo celular em um mesmo ensaio se mostrou interessante dentro da pesquisa envolvendo sistema nervoso central. Finalmente, estudos adicionais com os novos protótipos a fármacos (IHT1009 e IHT12127) são necessários para a obtenção de dados mais conclusivos sobre seu potencial citoprotetor mais direcionado para os astrócitos em relação às células neuronais PC-12.
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    Clinical variables related to the diagnostic stability of demential syndromes
    (Cambridge Univ Press, 2017) de Moraes, Fabiano Moulin [UNIFESP]; Ferreira Bertolucci, Paulo Henrique [UNIFESP]
    Background: Assigning a diagnosis to a patient with dementia is important for the present treatment of the patient and caregivers, and scientific research. Nowadays, the dementia diagnostic criteria are based on clinical information regarding medical, history, physical examination, neuropsychological tests, and supplementary exams and, therefore, subject to variability through time. Methods: A retrospective observational study to evaluate variables related to clinical diagnostic stability in dementia syndromes in at least one year follow up. From a sample of 432 patients, from a single university center, data were collected regarding sociodemographic aspects, Clinical Dementia Rating, physical examination, neuropsychological tests, and supplementary exams including a depression triage scale. Results: From this sample, 113 (26.6%) patients have their diagnosis changed, most of them adding a vascular component to initial diagnosis or depression as comorbidity or main disease. Our findings show that many factors influence the diagnostic stability including the presence of symmetric Parkinsonism, initial diagnosis of vascular dementia, presence of diabetes and hypertension, the presence of long term memory deficit in the neuropsychological evaluation, and normal neuroimaging. We discuss our findings with previous findings in the literature. Conclusion: Every step of the clinical diagnosis including history, vascular comorbidities and depression, physical examination, neuropsychological battery, and neuroimaging were relevant to diagnosis accuracy.
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    The Contribution of Supplementary Tests in the Differential Diagnosis of Dementia
    (Sage Publications Inc, 2018) de Moraes, Fabiano Moulin [UNIFESP]; Bertolucci, Paulo Ferreira [UNIFESP]
    Introduction: Supplementary tests are part of the clinical approach to diagnose cognitive impairment. We aimed to determine the role of supplementary examinations, except for biomarkers, on diagnostic stability of dementia over time and to identify reversible dementias. Methods: We identified 432 patients with dementia who performed 2 clinical evaluations and the supplementary examinations recommended by the American Academy of Neurology in a follow-up period of 1 year. Results: In this sample, 110 (24.5%) patients changed their diagnosis at 1-year follow-up for the appearance of vascular cognitive impairment than the initial diagnosis, due to the neuroimaging. Concerning the reversible dementias, depression was the major differential diagnosis, detected in 13 (81%) of the 16 patients with cognitive improvement. Conclusion: Therefore, regarding the supplementary examinations only neuroimaging and the depression triage were relevant for clinical practice regarding the differential diagnosis of dementia.
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    As estratégias de agrupamentos na fluência verbal animais e frutas na doença de alzheimer leve
    (Universidade Federal de São Paulo (UNIFESP), 2014-07-30) Giacominelli, Carla [UNIFESP]; Bertolucci, Paulo Henrique Ferreira Bertolucci [UNIFESP]; Universidade Federal de São Paulo (UNIFESP)
    Objective: To investigate patterns of clusters in Semantic Verbal Fluency Task- animals (SVFT-a) and the Semantic Verbal Fluency Task Fruits (SVFT-f) on control group and compare them to subjects with Mild Alzheimer's disease (MAD). Methods: This was a cross-sectional study with two samples. The sample of SVFT-a, consisted of 400 healthy elderly and 180 elderly with MAD. The sample of SVFT-f, consisted of 180 normal elderly and 80 subjects with MAD. Both subjects were: age ? 60 and ? 85 years schooling, 1-4; 5-8 and> 9. The controls were non-demented and without psychiatric complaints. The evaluation protocol, constituted MMSE within normal limits for the controls (Brucki), SVFT-a (Brucki et al, 1997), SVFT-f, the Clock Drawing Test (Shulman et al, 1986; and The Lawton Instrumental Acti vities of Daily Living (IADL). The MAD group had CDR-1 and MMSE> 20. Results: Both SVFT discriminated well the MAD and CG (AUC> 0.08 and p> 0.001). The one that failed to discriminate them was TFVSF-number of clusters. Concerning age, the analysis revealed differences in the accuracy of the SVFT. The SVFT-a accuracy increased with age and on SVFT-f, moderately decreased, and which was quite predictive in 60-69 years (AUC = 0.08, p <0.0001). The most common strategy of SVFT in CG was based on semantic aspects (95%), followed by phonemic (18%). MAD made semantic clusters (5%) and phonemic clusters (38%). The clustering strategy in SVFT-f, was not based on semantic aspects, but on articulation point (p> 0.001) of Brazilian Portuguese. Also, the bilabial ([p],[b]and[m]) articulation point (98% - CG, 2%-DAL) was associated with a higher total score on SVFT-f (p <0.0001) and the velar point ( [k] and [g] ) with lowers scores on SVFT-f (2%-CG and 98% DAL). Conclusions: Although the quantitative score proved to be more sensitive in MAD group, qualitative scoring revealed differences in structuring subsets of groups in SVFT, suggesting a hierarchy within the Declarative Memory and also a differentiation of accuracy for age. The SVFT and their qualitative scores, tell us about the process of data acquisition and linguistic aspects of deterioration in AD.
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    Relação do uso de suplemento alimentar com a capacidade funcional de idosos e de pacientes com doença de alzheimer
    (Universidade Federal de São Paulo (UNIFESP), 2015-10-30) Kamikado, Glaucia Akiko [UNIFESP]; Bertolucci, Paulo Henrique Ferreira Bertolucci [UNIFESP]; Universidade Federal de São Paulo (UNIFESP)
    Objectives: To evaluate if the nutrition supplementation improves strength, muscle endurance, independence and quality of life of patients with Alzheimer's disease compared to healthy elderly with and without supplementation. Methods: A randomized, prospective 6-month study which enrolled 60 subjects individuals of both genders, divided into 3 groups : Healthy Elderly Control Group (HECG), healthy elderly Group Supplement (HEGS) and Alzheimer's disease Supplement Group (ADG) with clinical dementia rating 1 and 2 (CDR). The subjects attended were from the Behavioral Neurology Clinic of UNIFESP and neighborhood. All were evaluated for nutritional anamnesis, evaluation of anthropometric data, time up go, right and left dynamometry, scale of Functional Independence Measure and quality of life. The MMSE and CDR were the parameters of cognitive screening and staging of the disease. Completed the study 54: 20 healthy elderly control group, 17 healthy elderly supplement group and 17 belonging to the AD supplement group. The subjects supplemented received two daily doses of oral proteic caloric supplementation, during six months of the study. Six patients were excluded the sample because they could not attend to all queries. Results: Anthropometric data in both supplemented groups (healthy elderly and Alzheimer's disease) showed statistically significant results in body mass index compared to control group. When analyzed parameters related to muscle mass, no group had improvement. The increase in body mass index, was due to the increase in adipose tissue. The time up go showed that the three groups began the study with time for performing the route greater than expected and that the use of proteic caloric supplement improved the march of the supplemented groups. Were not observed in all groups improves in upper limbs strength. The functional scale of independence and life quality, showed a statistically significant improvement for Alzheimer's Disease supplement group. Conclusion: Although the sample size was small, the use of a nutritional supplement is indicated for both elderly and patients with Alzheimer´s disease as a means of nutritional intervention, since it significantly improves the nutritional status, functional independence and quality of life.
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    Relações entre controle executivo e memória episódica verbal no comprometimento cognitivo leve e na demência tipo Alzheimer
    (Programa de Pós-graduação em Psicologia, Universidade Federal do Rio Grande do Norte, 2005-04-01) Hamdan, Amer Cavalheiro; Bueno, Orlando Francisco Amodeo [UNIFESP]; Universidade Federal do Paraná; Universidade Federal de São Paulo (UNIFESP)
    This study compared and related the performance of older people with Mild Cognitive Impairment and Alzheimer-type dementia in tests of executive control and of verbal episodic memory. In the evaluation of the verbal episodic memory we used the Task of Immediate Word Recall and the Task of Delayed Word Recall. In the evaluation of executive control we used the following tests: Random Number Generation, Trail Making Test, Semantic and Phonological Verbal Fluency, Wisconsin Card Sorting Test, Reading Span Test, and Brow-Peterson Test. Thirteen elders of the control group were compared by age and education with nine elders with Mild Cognitive Impairment and eight elders with Alzheimer-type dementia. Differences and significant statistical associations were found in relation to the tests of executive control with the groups investigated. Despite the presence of significant associations between the verbal episodic memory and the executive control, deficits of the executive control were not evidenced in groups with Mild Cognitive Impairment.