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Presymptomatic Testing for Adult-onset Neurological Disorders: An Analysis of PracticeFairbrother, Laura 18 September 2012 (has links)
No description available.
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Preservation of self in people with dementia living in residential care: A socio-biographical approachSurr, Claire A. January 2006 (has links)
No / The maintenance of self in dementia is associated with socio-biographical factors. The theoretical literature suggests that interpersonal relationships, the social context, and the generation of stories are important in maintenance of self. Empirical research on self in dementia supports this but has been predominantly conducted with participants living in the community. Living in residential care brings additional threats to self. This paper presents a study examining the relevance of a socio-biographical theory of self to people with dementia living in residential care. Between 3 and 8 tape-recorded and transcribed unstructured interviews were conducted with 14 people with dementia who were living in 4 residential homes throughout England and Wales, over a 6-24-month period. They were analysed using an interpretive biographical methodology. The results provide evidence to support the relevance of a socio-biographical theory of self to this group. Relationships with family, other residents and care home staff were important for maintenance of self. Social roles related to work, being part of a family, caring for others and being cared for, were particularly significant for self in this group. The creation of a life story, stories of selected life events, and the telling of stories with possible metaphorical interpretations were also important for the maintenance of self. The results also suggest that psychological and embodied factors may be relevant to the self in dementia. The study suggests that staff working in residential homes should consider these elements if they are to provide care that supports maintenance of self for people with dementia. Implications for future research are discussed.
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"Espectroscopia de prótons na demência de Alzheimer e no comprometimento cognitivo" / Proton spectroscopy in Alzheimer's dementia and amnestic mild cognitive impairmentSouza, Andrea Silveira de 12 December 2005 (has links)
Estudamos os achados da espectroscopia de prótons no córtex parietal-cíngulo posterior e das escalas MEEM, BRDS e FAST em pacientes com doença de Alzheimer - DA, comprometimento cognitivo amnéstico - CCA e controles normais - CN. Apenas as razões NAA/Cr e MI/NAA diferenciaram (p < 0.002) os grupos DA e CN. Houve correlação significativa do NAA/Cr e do MI/NAA com o BRDS (pontuação total - PT; atividades cotidianas - AC) e FAST, e do MI/NAA com o MEEM. Houve acréscimo de 5% na especificidade (CN x DA; CN x CCA), e de 2.4% (CN x DA) e 3.4% (CN x CCA) na acurácia diagnóstica, ao adicionar as razões NAA/Cr e MI/NAA às escalas BRDS (PT e AC) e FAST, aumentando a detecção de indivíduos com CCA e DA / We studied the findings of proton spectroscopy of the posterior parietal-cingulate cortex, and of MMSE, BRDS and FAST scales in subjects with Alzheimer disease - AD, amnestic mild cognitive impairment - MCI-A and normal controls - NC. Only NAA/Cr and MI/NAA differentiated (p < 0.002) the AD and NC groups. Significant correlation was found between NAA/Cr and MI/NAA with BRDS (total score - TS; everyday activities - EA) and FAST scales, and between MI/NAA and MMSE. Specificity increased in 5% (NC x AD; NC x MCI-A) and diagnostic accuracy in 2.4% (NC x AD) and 3.4% (NC x MCI-A) when NAA/Cr and MI/NAA ratios were added up to BRDS (TS & EA) and FAST scales, increasing MCI-A and AD detectability
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"Espectroscopia de prótons na demência de Alzheimer e no comprometimento cognitivo" / Proton spectroscopy in Alzheimer's dementia and amnestic mild cognitive impairmentAndrea Silveira de Souza 12 December 2005 (has links)
Estudamos os achados da espectroscopia de prótons no córtex parietal-cíngulo posterior e das escalas MEEM, BRDS e FAST em pacientes com doença de Alzheimer - DA, comprometimento cognitivo amnéstico - CCA e controles normais - CN. Apenas as razões NAA/Cr e MI/NAA diferenciaram (p < 0.002) os grupos DA e CN. Houve correlação significativa do NAA/Cr e do MI/NAA com o BRDS (pontuação total - PT; atividades cotidianas - AC) e FAST, e do MI/NAA com o MEEM. Houve acréscimo de 5% na especificidade (CN x DA; CN x CCA), e de 2.4% (CN x DA) e 3.4% (CN x CCA) na acurácia diagnóstica, ao adicionar as razões NAA/Cr e MI/NAA às escalas BRDS (PT e AC) e FAST, aumentando a detecção de indivíduos com CCA e DA / We studied the findings of proton spectroscopy of the posterior parietal-cingulate cortex, and of MMSE, BRDS and FAST scales in subjects with Alzheimer disease - AD, amnestic mild cognitive impairment - MCI-A and normal controls - NC. Only NAA/Cr and MI/NAA differentiated (p < 0.002) the AD and NC groups. Significant correlation was found between NAA/Cr and MI/NAA with BRDS (total score - TS; everyday activities - EA) and FAST scales, and between MI/NAA and MMSE. Specificity increased in 5% (NC x AD; NC x MCI-A) and diagnostic accuracy in 2.4% (NC x AD) and 3.4% (NC x MCI-A) when NAA/Cr and MI/NAA ratios were added up to BRDS (TS & EA) and FAST scales, increasing MCI-A and AD detectability
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Analysis of biomarkers for complex human diseasesAnsari, Morad January 2009 (has links)
The aims of this study were to analyse known and potential biomarkers of common and genetically complex human disorders and to identify genetic and environmental variation associated with plasma biomarker concentrations. Two groups of protein biomarkers were analysed. First, plasma complement factor H (CFH) was selected as a potential biomarker for age-related macular degeneration (AMD), since common variants in the CFH gene show strong association with this disorder. Secondly, two isoforms of amyloid-β (Aβ40 and Aβ42) were selected as biomarkers for Alzheimer disease (AD) since Aβ deposits are major constituents of the amyloid plaques characteristic of this disorder. Physiological and anthropometric measurements and samples of human and genomic DNA were collected from a population sample of 1,021 individuals from the Croatian island of Vis. Quantitative determination of plasma Aβ40 and Aβ42 concentrations was performed using enzyme-linked immunosorbent assays. Heritabilities and significant covariate effects were estimated for each trait in the Croatian data set. Genome-wide linkage and association analyses were conducted for the biomarker traits. A novel finding was the genome-wide significant association between a CFH and several polymorphisms close to and within the CFH gene. The strongest association was with an intronic SNP within CFH, which explained 28% of the total trait variance (P < 10-50). The association was also replicated in a Dutch sample set. A SNP haplotype was identified which accounted for a higher proportion of the phenotypic variance. Conditional haplotype analysis showed that the effect of this haplotype on plasma CFH concentration was independent of the CFH Y402H variant, and significantly stronger than a deletion of the adjacent CFHR3/CFHR1 which was already known to affect AMD susceptibility. Genetic analysis of 382 AMD cases and 201 controls was consistent with the CFH Y402H variant being the strongest AMD susceptibility locus. Variation in plasma CFH concentration was found to explain up to 1.8% of the variation in susceptibility to AMD with an odds 2.1 (95% C.I. 1.3-3.4, P = 0.003). SNPs that were strongly associated with a CFH concentration also influenced AMD susceptibility (P < 0.05) independently of the CFH Y402H polymorphism. Functional analysis of genomic regions associated with plasma CFH is needed to identify the causal variants. Associations were observed between plasma Aβ40 concentration and several novel candidate loci, spanning regions of approximately 0.2 Mb, on chromosomes 9 and X. Similarly, novel associations with plasma Aβ42 were found in several regions, each spanning 0.2-0.4 Mb, on chromosomes 2, 5, 9, 15 and 20. The proportion of the phenotypic variance in plasma Aβ42 explained by these putative associations ranged between 1.8 and 2.8%. However, none of the associated SNPs was significant after correction for multiple testing, therefore replication is required. Finally, attempts were made to identify and quantitate new protein biomarkers of disease in human plasma using mass spectrometry. Development and optimisation of techniques was initially undertaken to deplete high-abundance plasma proteins and improve signal:noise ratio. This allowed the assessment of downstream proteomic approaches including MALDI-TOF mass spectrometry (MS), capillary electrophoresis (CE) and ion exchange chromatography (IEC), each with the potential for large-scale quantitation of plasma proteins. Although the analysis of single protein analytes, using CE and IEC proved promising, the results highlighted the difficulty associated with MALDI-TOF and protein ionisation techniques in analysing complex mixtures such as plasma.
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Etude de l'intéraction de la thioflavine T et de complexes de ru(ii) avec le peptide amyloïde bêta dans le cadre de la maladie d'alzheimer / Interaction study of thioflavin T and ru(ii) complexes with the amyloid beta peptide linked with the Alzheimer diseaseEury, Hélène 16 December 2013 (has links)
La maladie d'Alzheimer est caractérisée par la présence de dégénérescences neurofibrillaires et l'accumulation de plaques amyloïdes dans le cerveau. Ces plaques contiennent principalement un peptide nommé amyloïde-β (Aβ) sous forme agrégée. Le processus d'agrégation des peptides Aβ en plaques amyloïdes représente une étape clé dans l'apparition de la pathologie, la coordination du cuivre, et également du zinc, favorisant la formation d'espèces agrégées impliquées dans la neurotoxicité. Notre objectif consiste à concevoir des complexes bifonctionnels avec d'une part un analogue de la Thioflavine T (ThT) et d'autre part un complexe de Ru(II), ce travail de thèse s'articule donc selon ces deux axes. I- Nous nous sommes d'abord intéressés à l'interaction entre le peptide Aβ et la Thioflavine T (ThT), fluorophore classiquement utilisé pour étudier l'agrégation du peptide Aβ. Cette interaction a été étudiée principalement par spectroscopie RMN. Les résultats obtenus ont permis d'identifier le site d'interaction de la ThT au peptide Aβ. Par la suite, les effets de la ThT et du Zn(II) sur l'agrégation du peptide Aβ ont été évalués en combinant la RMN et la spectroscopie de fluorescence. A partir des données obtenues, nous avons montré que la ThT et le Zn(II) ne sont pas inertes sur la cinétique d'agrégation du peptide Aβ. Les résultats ont également révélé des différences importantes concernant les informations apportées par la fluorescence et la RMN. II- La coordination du cuivre et du zinc implique principalement les noyaux imidazoles des résidus histidines. Afin d'empêcher la coordination de ces ions métalliques aux peptides Aβ, une stratégie thérapeutique innovante consiste en l'utilisation de complexes platinoïdes comportant des sites labiles et capables de se lier aux résidus histidines du Aβ. En raison de la toxicité des complexes de Pt(II), nous avons envisagé la synthèse de complexes de Ru(II), principalement basés sur le motif fac-Ru(CO)32+. Différents complexes avec des ligands de type glycinate, hydroxyquinolinate et éthylenediamine ont été synthétisés. L'étude de leur interaction avec le peptide Aβ a été réalisée par différentes techniques spectroscopiques (RMN, RPE, fluorescence, spectrométrie de masse). Les résultats obtenus ont montré, en particulier, que les complexes sont capables d'inhiber l'agrégation du peptide Aβ induite par le zinc. / The Alzheimer's disease is characterized by the presence of neurofibrillary tangles and amyloid plaques in the brain. These plaques are formed by aggregated amyloid-β (Aβ) peptide. The Aβ aggregation represents a key event in the appearance of the pathology, copper and zinc coordination favoring the formation of aggregated species involved in the neurotoxicity. Our objective consists in designing bifonctional complexes with, on one hand, a Thioflavine T (ThT) analog and, on the other hand, a Ru(II) complex : this thesis is thus centered around these two axes. I- In this context, we first investigated the interaction between Aβ and ThT, which is a classical dye commonly used to study the aggregation process. This interaction was mainly studied by NMR spectroscopy. Our first results allowed us to identify the interaction site of the ThT with the Aβ peptide. Then, the ThT and Zn(II) effects on the aggregation process were assessed by NMR and fluorescence spectroscopy. From the obtained data, we showed that ThT and Zn (II) are involved in the aggregation kinetic. The results also revealed important differences concerning the information brought by fluorescence and NMR. II- Copper and zinc coordination mainly implies imidazole ring of the histidine residues. In order to prevent the coordination of these metallic ions to Aβ, an innovative therapeutic strategy consists of the use of platinoid complexes containing labile sites which are able to bind the Aβ histidine residues. Because of Pt(II) complexes toxicity, we envisaged the synthesis of Ru(II) complexes, mainly based on fac-Ru(CO)32+ motive. Different complexes with glycinate, hydroxyquinolinate or ethylenediamine ligand were synthesized. The study of their interaction with the Aβ peptide was realized by various spectroscopy techniques (RMN, RPE, fluorescence, mass spectrometry and demonstrated that the complexes are able to prevent the Aβ aggregation induced by zinc.
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Etude du métabolisme des pyramides du néocortex dans un modèle murin de la maladie d'Alzheimer - voies de signalisations impliquées dans la modulation de l'excitabilité des pyramides du néocortex par la noradrénaline / Study of neocortical pyramidal cells' metabolism in a mouse model of Alzheimer's disease - Signaling pathways involved in the modulation of neocortical pyramidal cells' excitability by noradrenalinePiquet, Juliette 05 July 2017 (has links)
Mes travaux de thèse se sont portés sur les cellules pyramidales du néocortex de rongeur, en condition normale et pathologique. L'altération précoce du métabolisme du glucose est une caractéristique fonctionnelle invariante de la maladie d'Alzheimer (MA) qui pourrait être à l'origine des dysfonctionnements synaptiques et de la neurodégénerescence tardive associés à la maladie. Pour mieux comprendre la pathogenèse de la MA, j'ai cherché à clarifier les mécanismes responsables de l'hypométabolisme précoce du glucose observé dans la maladie. Mes travaux ont mis à jour des altérations des flux métaboliques du glucose chez un modèle murin de la MA à un stade asymptomatique juvénile. Les données d'imagerie cellulaire révèlent une augmentation du flux glycolytique associée à une diminution de l'activité de la voie des Pentoses Phosphates dans les cellules pyramidales néocorticales des souris 3xTg-AD sans altération du transport du glucose. Le système noradrénergique exerce une profonde influence sur les processus cognitifs. Une partie de ma thèse a été consacrée à éclaircir les effets de la NA sur la modulation de l'excitabilité des cellules pyramidales dans le cortex somatosensoriel de souris. Mes résultats montrent que les agonistes α1 et β noradrénergiques inhibent les courants responsables de l'hyperpolarisation lente qui suit les potentiels d'actions et suggèrent un effet coopératif des récepteurs α1 et β noradrénergiques. L'implication des récepteurs α1 dans la genèse d'une dépolarisation lente post PA reste à déterminer. Ces deux phénomènes convergeraient vers une dépolarisation accrue de la membrane du neurone, facilitant une nouvelle décharge de PA. / During my thesis, I focused on the neocortical pyramidal cells in normal and pathological condition. The early alteration of glucose metabolism is an invariant feature of Alzheimer's disease ( AD) which might lead to the late synaptic dysfunctions and neuronal loss related to the pathology. To better understand the AD pathogenesis, I sought to clarify the mechanisms responsible for the early glucose hypometabolism observed in the pathology. This work has highlighted alterations in glucose fluxes at a juvenile presymptomatic stage in a mouse model of AD. The cellular imaging data revealed an increase of the glycolytic pathway associated with a reduction in the PPP in pyramidal neurons of 3xTg-AD mice without any alteration of glucose transport. The noradrenergic system has a significant influence on cognitive processes. A part of my thesis has been devoted to highlight the effect of noradrenaline on pyramidal cells' excitability in the mouse somatosensory cortex. My results show that α1 and β noradrenergic agonists inhibit the currents responsible for sAHP and suggest a cooperative effect of α1 and β noradrenergic receptors. The RA-α1 involvement in the genesis of a slow After Depolarization has yet to be determined. Those two phenomena will lead to an increased depolarization of neuronal membrane, facilitating a novel action potential discharge.
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Aplicação de redes neurais artificiais paraconsistentes como método de auxílio no diagnóstico da doença de Alzheimer / Application of artificial neural networks paraconsistents as a method of aid in the diagnosis of Alzheimer diseaseLopes, Helder Frederico da Silva 02 July 2009 (has links)
A análise visual do eletroencefalograma (EEG) tem se mostrado útil na ajuda diagnóstica da doença de Alzheimer (DA), sendo indicado em alguns protocolos clínicos quando o diagnóstico permanece em aberto após a avaliação inicial. Porém, tal análise está sujeita naturalmente à imprecisão inerente de equipamentos, movimentos do paciente, registros elétricos e variação da interpretação da análise visual do médico. A teoria das Redes Neurais Artificiais (RNA) tem-se mostrado muito apropriado para tratar problemas como predição e reconhecimento de padrões de sinais em outras áreas do conhecimento. Neste trabalho utilizou-se uma nova classe de RNA, a Rede Neural Artificial Paraconsistente (RNAP), caracterizada pela manipulação de informações incertas, inconsistentes e paracompletas, destinada a reconhecer padrões predeterminados de EEG e de avaliar sua aplicabilidade como método auxiliar para o diagnóstico da DA. Trinta e três pacientes com DA provável e trinta e quatro pacientes controles foram submetidos ao registro de exames de EEG durante a vigília em repouso. Considerou-se como padrão normal de um paciente, a atividade de base entre 8,0 Hz e 12,0 Hz (com uma frequência média de 10 Hz), permitindo uma variação de 0.5 Hz. A RNAP foi capaz de reconhecer ondas de diferentes bandas de frequência (teta, delta, alfa e beta) aplicadas ao uso clínico do EEG, levando a uma concordância com o diagnóstico clínico de 82% de sensibilidade e 61% de especificidade. Com estes resultados, acredita-se que a RNAP possa vir a ser uma ferramenta promissora para manipular análise de EEG, tendo em mente as seguintes considerações: o interesse crescente de especialistas em análise visual de EEG e a capacidade da RNAP tratar diretamente dados imprecisos, inconsistentes e paracompletos, fornecendo uma interessante análise quantitativa e qualitativa / The visual analysis of EEG has shown useful in helping the diagnosis of Alzheimer disease (AD) when the diagnosis remains uncertain, being used in some clinical protocols. However, such analysis is subject to the inherent equipment imprecision, patient movement, electrical records, and physician interpretation of the visual analysis variation. The Artificial Neural Network (ANN) could be a helpful tool, appropriate to address problems such as prediction and pattern recognition. In this work, it has use a new class of ANN, the Paraconsistent Artificial Neural Network (PANN), which is capable of handling uncertain, inconsistent, and paracomplet information, for recognizing predetermined patterns of EEG and to assess its value as a possible auxiliary method for AD diagnosis. Thirty three patients with Alzheimer\'s disease and thirty four controls patients of EEG records were obtained during relaxed wakefulness. It was considered as normal patient pattern, the background EEG activity between 8.0 Hz and 12.0 Hz (with an average frequency of 10 Hz), allowing a range of 0.5 Hz. The PANN was able to recognize waves that belonging to their respective bands of clinical use (theta, delta, alpha, and beta), leading to an agreement with the clinical diagnosis at 82% of sensitivity and at 61% of specificity. Supported with these results, the PANN could be a promising tool to manipulate EEG analysis, bearing in mind the following considerations: the growing interest of specialists in EEG analysis visual and the ability of the PANN to deal directly imprecise, inconsistent and paracomplet data, providing an interesting quantitative and qualitative analysis
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Mini-addenbrookes cognitive examination (M-ACE) como instrumento de avaliação cognitiva breve no comprometimento cognitivo leve e doença de Alzheimer leve / Mini-addenbrooke\'s cognitive examination (M-ACE) as a tool for brief cognitive assessment in mild cognitive impairment and mild Alzheimer\'s diseaseMiranda, Diane da Costa 28 June 2018 (has links)
INTRODUÇÃO: A Mini-Addenbrooke\'s Cognitive Examination (M-ACE) consiste em um teste de avaliação cognitiva breve composta de cinco itens que visam avaliar quatro domínios cognitivos principais (orientação, memória, linguagem e função viso-espacial) com pontuação máxima de 30 pontos e um tempo de administração de cinco minutos. OBJETIVO: Avaliar o desempenho de idosos cognitivamente saudáveis, com CCL e DA leve na versão brasileira da M-ACE. MÉTODOS: o teste foi aplicado um grupo de 23 pacientes com DA provável leve, 36 CCL e 25 idosos cognitivamente saudáveis. Todos os participantes incluídos tinham idade >= 60 anos. Foram excluídos pacientes com demência de intensidade moderada ou grave, demência de outra etiologia, comorbidades graves com potencial de comprometer a cognição e uso de medicação psicotrópica. A acurácia do teste foi avaliada por meio da análise das curvas ROC. Para analisar a relação entre os escores da M-ACE e os demais testes cognitivos aplicados foram utilizados os coeficientes de correlação de Spearman. Para analisar a consistência interna da M-ACE e suas três versões foi utilizado o coeficiente alfa de Cronbach. RESULTADOS: Houve um predomínio do gênero feminino, a média de idade foi de 73 anos, com faixa etária predominante de 60-69 anos. A média de escolaridade obtida foi de 11 anos. A M-ACE apresentou alta consistência interna (alfa de Cronbach > 0,8; IC 95% 0,776 a 0,869) e mostrou ser extremamente capaz de diferenciar o grupo DA dos demais participantes, com uma acurácia superior ao MEEM. O ponto de corte de 20 foi o de maior sensibilidade e especificidade (95,6% e 90,16% respectivamente), com área sob a curva considerada alta (ASC = 0,805; IC 95% 0,705 -0,904). A M-ACE apresentou melhor precisão em diferenciar os três grupos quando comparado com o MEEM (71,43 versus 60,71). Observou-se ainda uma precisão mais robusta em diferenciar DA de CCL com a M-ACE (63,89 versus 30,56 no MEEM). O escore total da M-ACE não sofreu considerável influência da idade e escolaridade. A M-ACE apresentou forte correlação com MEEM (cor = 0,78), bem como todos os itens (exceto percepção) da BBRC e QAF (cor = -0,76). CONCLUSÃO: A M-ACE pode ser considerada um teste rápido de rastreio com elevada acurácia no diagnóstico de DA. O ponto de corte sugerido neste estudo é de 20 para DA e 27 para CCL / INTRODUCTION: The Mini-Addenbrooke\'s Cognitive Examination (M-ACE) consists of a brief cognitive assessment test composed of five items that aim to evaluate four main cognitive domains (orientation, memory, language and visuospatial function) with a maximum score of 30 points and a time of administration of five minutes. OBJECTIVE: Evaluate the performance of cognitively healthy elderly, MCI and mild AD in the Brazilian version of M-ACE. METHODS: The test was applied to a group of 23 patients with mild probable AD, 36 MCI and 25 cognitively healthy elderly. All included participants were aged >= 60 years. Patients with moderate or severe dementia, dementia of another etiology, severe comorbidities with potential to compromise cognition and use of psychotropic medication were excluded. The accuracy of the test was evaluated by analyzing the ROC curves. Spearman\'s correlation coefficients were used to analyze the relationship between the M-ACE scores and the other cognitive tests applied. In order to analyze the internal consistency of the M-ACE, the Cronbach\'s alpha coefficient was used. RESULTS: There was a predominance of females, mean age was 73 years, with a predominant age range of 60-69 years. The average level of schooling was 11 years. MACE presented high internal consistency (Cronbach\'s alpha > 0.8, 95% CI 0.776 to 0.869) and showed to be extremely capable of differentiating the AD group from the other participants, with a higher accuracy than the MMSE. The cutoff point of 20 was the one with the highest sensitivity and specificity (95.6% and 90.16%, respectively), with an AUC considered to be high (AUC = 0.805, 95% CI 0.705-0.904). The M-ACE presented better accuracy in differentiating the three groups when compared to the MMSE (71.43 versus 60.71). It was also observed a more robust precision in differentiating DA of MCI with M-ACE (63.89 versus 30.56 in MMSE). The total M-ACE score was not very influenced by age and schooling. M-ACE showed a strong correlation with MMSE (spearman = 0.78), as well as all items (except perception) of BBRC and QAF (spearman = -0.76). CONCLUSIONS: M-ACE can be considered a brief screening tool with high accuracy in the diagnosis of AD. The cutoff point suggested in this study is 20 for AD and 27 for MCI
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Efeitos do lítio sobre a expressão e atividade das enzimas fosfolipase A2 e glicogênio sintase quinase 3beta e sua relação com o estado de fosforilação da proteína tau / Effects of lithium on the expression of the enzymes activity phospholipase A2 and glycogen synthase kinase 3beta and its relationship with the phosphorylation state of tau proteinPaula, Vanessa de Jesus Rodrigues de 11 August 2015 (has links)
O presente estudo comparou o efeito do tratamento crônico com lítio em doses subterapêuticas (0,02mM e 0,2mM) e dose terapêutica (2mM) em cultura primária de neurônios corticais e hipocampais. As amostras foram analisadas e comparadas com o grupo controle (sem tratamento) tanto para os neurônios corticais, como para os neurônios hipocampais. O objetivo do estudo foi: 1) avaliar, nessas culturas celulares, a atividade de diferentes quinases (PKA, CaMKII, AKT e GSK3beta), diferentes sítio de fosforilação da Tau (Ser, 199, 205, 214, 396, C-terminal e seis isoformas), a partir da inibição da PLA2 pelo lítio; 2) Investigar as vias de sinalização envolvidas na modulação do estado de fosforilação da proteína tau a partir da inibição da PLA2 em culturas primárias de neurônios; 3) avaliar, simultaneamente, a expressão de fatores neurotróficos (BDNF) e citocinas (GM-CSF, IL-1b, IL-2, IL-4, IL-5, IL6, IL-10, IL-12, IFN-y e TNF-alfa) mediante o tratamento de neurônios primários com lítio e 4) avaliar expressão gênica por microarray das culturas tratadas com diferentes doses, subterapêuticas e terapêutica, de cloreto de lítio. Nossos resultados sugerem uma dissociação de efeitos em neurônios corticais dos observados em neurônios hipocampais. O lítio aumentou a atividade enzimática da iPLA2 e da cPLA2, tanto em neurônios corticais como em neurônios hipocampais. A atividade da GSK3beta foi inibida pelo tratamento crônico com lítio em neurônios hipocampais e apresentou efeito contrário em neurônios corticais. Observamos comportamentos diferentes das diferentes proteínas analisadas em culturas de neurônios corticais e hipocampais, e não tivemos significância estatística para as alterações na proteína tau. O tratamento nas doses subterapêuticas aumentou a secreção de citocinas pró-inflamatórias tanto em neurônios corticais quanto em neurônios hipocampais / The present study compared the effect of lithium chronic treatment with subtherapeutic doses (0.02mM and 0.2mM) and therapeutic dose (2mM) in primary cortical and hippocampal neurons cell culture. This samples were analyzed and compared with the control group (no treatment). The study\'s goal was: 1) to evaluate in these Cell Culture a different activity kinases (PKA, CaMKII, AKT and GSK3beta), different phosphorylation site of the Tau (199, 205, 214, 396, C-terminal and Six isoforms) and PLA2 inhibition; 2) To investigate how signaling pathways involved in modulation of tau phosphorylation from the inhibition of PLA2 in primary cultures of neurons; 3) analyze an expression of neurotrophic factors (BDNF) and cytokines (GM-CSF, IL-1b, IL-2, IL-4, IL-5, IL-6, IL-10, IL-12, IFNy TNFalfa 4) to evaluate gene expression via microarray with different doses of lithium treatment. Our results suggest a dissociation effects on cortical and hippocampal neurons cell culture. Lithium increased the enzyme activity of iPLA2 and cPLA2, in both cortical and hippocampal neurons. The GSK3beta the activity was inhibited by chronic treatment with lithium in hippocampal neurons and presented contrary effect on cortical neurons. We observe not statistics significance on tau protein. The treatment at subtherapeutic and therapeutic doses increased the secretion of pro and anti-inflammatory cytokines both in cortical and hippocampal neurons
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