Search

Background The diagnosis of cognitive disorders in Parkinson disease (PD) can be very challenging. Aiming at establishing uniform and reliable diagnostic procedures, the International Parkinson’s Disease and Movement Disorder Society (MDS) commissioned task forces to delineate diagnostic criteria for mild cognitive impairment (MCI) and dementia in PD. Objectives To investigate the applicability of the MDS recommendations for cognitive evaluation in a Brazilian sample of patients with PD with low levels of formal education. Methods A total of 41 patients with PD were subjected to a comprehensive neuropsychological evaluation based on tests proposed by the MDS, which included the Mini-Mental State Examination, the Mattis Dementia Rating Scale (MDRS), the Trail Making Test (TMT) parts A and B, in addition to language and memory skills assessment. Neuropsychiatric and daily functioning features were also evaluated. Spearman correlation analyses were used to evaluate the association between the scores obtained in the cognitive scales and demographic/clinical variables. Results Although none of the participants had a formal diagnosis of dementia, 50% presented some degree of cognitive impairment when considering the results of the MDRS. Of note, a noticeable number of patients was not able to complete the full neuropsychological assessment. The TMT part B was the most difficult task, being completed by only 22 participants (54%). As expected, the greater the educational level, the better the performance on the cognitive tests. Better motor function was also associated with better scores in cognition. Conclusions Adopting strict inclusion/exclusion criteria and a comprehensive clinical evaluation, we found remarkable limitations for the MDS recommendations when individuals with low educational levels are considered. A revision of the current guidelines is necessary considering differences among populations, especially related to formal education. Resumo Antecedentes O diagnóstico de distúrbios cognitivos na doença de Parkinson (DP) pode ser muito desafiador. Com o objetivo de estabelecer procedimentos diagnósticos uniformes e confiáveis, a Sociedade Internacional da Doença de Parkinson e Distúrbios do Movimento (MDS, na sigla em inglês) encomendou forças-tarefa para delinear critérios diagnósticos para comprometimento cognitivo leve (CCL) e demência na DP. Objetivos Investigar a aplicabilidade das recomendações da MDS para avaliação cognitiva em uma amostra brasileira de pacientes com DP de baixa escolaridade. Métodos Um total de 41 pacientes com DP foram submetidos a uma avaliação neuropsicológica abrangente com base nos testes propostos pela MDS, que incluiu o Miniexame do Estado Mental, a Escala de Avaliação de Demência de Mattis (MDRS, na sigla em inglês), o teste de trilhas (TMT, na sigla em inglês) partes A e B, além da avaliação das habilidades de linguagem e memória. Características neuropsiquiátricas e de funcionamento diário também foram avaliadas. Análises de correlação de Spearman foram utilizadas para avaliar a associação entre os escores obtidos nas escalas cognitivas e variáveis demográficas/clínicas. Resultados Apesar de nenhum dos participantes ter diagnóstico formal de demência, 50% apresentaram algum grau de comprometimento cognitivo ao levar em consideração os resultados da MDRS. Vale ressaltar que um número notável de pacientes não conseguiu completar a avaliação neuropsicológica completa. A parte B do TMT foi a tarefa mais difícil, sendo realizada por apenas 22 participantes (54%). Como esperado, quanto maior o nível educacional, melhor o desempenho nos testes cognitivos. Melhor função motora também foi associada a melhores escores em cognição. Conclusões Adotando critérios rígidos de inclusão/exclusão e uma avaliação clínica abrangente, encontramos limitações marcantes para as recomendações da MDS quando considerados indivíduos com baixa escolaridade. É necessária uma revisão das diretrizes atuais considerando as diferenças entre as populações, principalmente relacionadas ao nível educacional.

To investigate the rates of diabetes mellitus (DM) and impaired fasting glucose (IFG) in a population-based sample of individuals aged 75 + years old and their associations with cognitive performance, depression, functionality, and quality of life (QoL).Overall, 350 people participated in the study. Assessments of cognition, mood, functionality and QoL were performed using the mini-mental state examination (MMSE), clock-drawing, category fluency tests, the Mini-International Neuropsychiatric Interview, Pfeffer's Functional Activities Questionnaire, and the WHO Quality of Life-Old (WHOQOL-OLD).IFG (ADA criteria) was identified in 42.1% of the sample, while the DM rate was 24.1%. Lack of knowledge of the DM diagnosis and lack of treatment occurred in 27% and 39% of the sample, respectively. Rates of dementia and depression, MMSE, category fluency scores, and previous cardiovascular events did not differ between the glycaemic groups. Individuals with DM performed worse on the clock-drawing test, functionality, and WHOQOL-OLD than the other participants. Individuals with IFG presented similar QoL and functionality when compared with the group without DM.IFG and DM were common in this population-based sample aged 75 + years old, as were inadequate diagnoses and treatments of DM. DM individuals presented poor performance in the executive function test, functionality, and QoL. Further studies are recommended to investigate the value of an IFG diagnosis among the most elderly population.

Due to the rudimentary antioxidant defenses in Trypanosoma cruzi, disruptors of redox balance are promising candidates for new antitrypanosomal drugs. We developed an integrated model based on systematic review, meta-analyses, and molecular modeling to evaluate the effect of trypanothione reductase (TR) inhibitors in T. cruzi infections. Our findings indicated that the TR inhibitors analyzed were effective in reducing parasitemia and mortality due to Trypanosoma cruzi infection in animal models. The most investigated drugs (clomipramine and thioridazine) showed no beneficial effects on the occurrence of infection-related electrocardiographic abnormalities or the affinity and density of cardiac β-adrenergic receptors. The affinity between the tested ligands and the active site of TR was confirmed by molecular docking. However, the molecular affinity score was unable to explain TR inhibition and T. cruzi death in vitro or the antiparasitic potential of these drugs when tested in preclinical models of T. cruzi infection. The divergence of in silico, in vitro, and in vivo findings indicated that the anti-T. cruzi effects of the analyzed drugs were not restricted to TR inhibition. As in vivo studies on TR inhibitors are still scarce and exhibit methodological limitations, mechanistic and highly controlled studies are required to improve the quality of evidence.