Treatment of Depression in Huntington's Disease: A Systematic Review.

Depression is a common psychiatric disorder among individuals with Huntington's disease (HD). Depression in HD and major depressive disorder appear to have different pathophysiological mechanisms. Despite the unique pathophysiology, the treatment of depression in HD is based on data from the treatment of major depressive disorder in the general population. The objective of this systematic review was to conduct a comprehensive evaluation of the available evidence. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines were followed. Studies on the treatment of depression in HD were identified by searching MEDLINE, Embase, and PsycInfo. The initial search yielded 2,771 records, 41 of which were ultimately included. There were 19 case reports, seven case series, three cross-sectional studies, one qualitative study, nine nonrandomized studies, and two randomized trials among the included studies. The most common assessment tools were the Hospital Anxiety and Depression Scale (N=8), the Beck Depression Inventory (N=6), and the Hamilton Depression Rating Scale (N=6). Only 59% of the included studies assessed depressive symptoms with a scoring system. The pharmacological options for the treatment of depression included antidepressants and antipsychotics. Nonpharmacological approaches were multidisciplinary rehabilitation, psychotherapy, and neurostimulation. Limited evidence on the treatment of depression in HD was available, and this literature consisted mainly of case reports and case series. This systematic review highlights the knowledge gap and the pressing need for HD-specific research to determine the efficacy of treatment approaches for depression in HD.

Obsessive-compulsive and perseverative behaviors in Huntington's disease.

Obsessive-compulsive and perseverative behaviors (OCBs/PBs) are characteristic features of Huntington's Disease (HD). Although a few recent research have attempted to discriminate between OCBs and PBs, most of the available evidence on OCBs does not consistently make this distinction. In this article, we aimed to explore the current inconsistencies in assessing and reporting OCBs/PBs and map the body of existing evidence. Up to half of the patients with motor manifest HD can experience OCBs. Separate reporting of PBs in HD patients has been uncommon among the studies and was frequently reported as a part of obsessive-compulsive symptoms. The structural limitation of the currently used rating scales and the overlaps in neuropathology and definition of OCBs and PBs are among the main reasons for the mixed reporting of OCBs/PBs. Perseverative thinking or behavior as a separate item is found in a few assessment tools, such as the Problem Behaviors Assessment - Short form (PBA-s). Even when the item exists, it is commonly reported as a composite score in combination with the obsessive-compulsive item. In addition to the significant psychological burden in individuals with HD, PBs are associated with somatic effects (e.g., cardiovascular symptoms) and high-risk behaviors (e.g., suicide). Recognition and monitoring of PBs in HD can aid in early detection of concerning symptoms and differentiating overlapping illnesses.

Plasma Exchange Reduces Aß Levels in Plasma and Decreases Amyloid Plaques in the Brain in a Mouse Model of Alzheimer's Disease.

Alzheimer's disease (AD) is the most common type of dementia, characterized by the abnormal accumulation of protein aggregates in the brain, known as neurofibrillary tangles and amyloid-ß (Aß) plaques. It is believed that an imbalance between cerebral and peripheral pools of Aß may play a relevant role in the deposition of Aß aggregates. Therefore, in this study, we aimed to evaluate the effect of the removal of Aß from blood plasma on the accumulation of amyloid plaques in the brain. We performed monthly plasma exchange with a 5% mouse albumin solution in the APP/PS1 mouse model from 3 to 7 months old. At the endpoint, total Aß levels were measured in the plasma, and soluble and insoluble brain fractions were analyzed using ELISA. Brains were also analyzed histologically for amyloid plaque burden, plaque size distributions, and gliosis. Our results showed a reduction in the levels of Aß in the plasma and insoluble brain fractions. Interestingly, histological analysis showed a reduction in thioflavin-S (ThS) and amyloid immunoreactivity in the cortex and hippocampus, accompanied by a change in the size distribution of amyloid plaques, and a reduction in Iba1-positive cells. Our results provide preclinical evidence supporting the relevance of targeting Aß in the periphery and reinforcing the potential use of plasma exchange as an alternative non-pharmacological strategy for slowing down AD pathogenesis.

Behavioral or neuropsychiatric symptoms of Alzheimer's disease: from psychopathology to pharmacological management.

Neuropsychiatric or behavioral symptoms of dementia encompass a series of disorders, such as anxiety, depression, apathy, psychosis, and agitation, all commonly present in individuals living with dementia. While they are not required for the diagnosis of Alzheimer's disease (AD), they are ubiquitously present in all stages of the disease, contributing to negative clinical outcomes, including cognitive decline, functional disability, and caregiver burden. Neuropsychiatric symptoms have been conceptualized not only as risk factors but as clinical markers of decline along the AD spectrum. The concept of "mild behavioral impairment", the behavioral correlate of mild cognitive impairment, has been proposed within this framework. The first steps in the management of behavioral symptoms in AD involve defining the target and investigating potential causes and/or aggravating factors. Once these factors are addressed, non-pharmacological approaches are preferred as first-line interventions. Following the optimization of anticholinesterase treatments, specific pharmacological approaches (e.g., antidepressants, antipsychotics) can be considered weighing potential side effects.

Sintomas neuropsiquiátricos ou comportamentais de demência envolvem uma série de condições, como ansiedade, depressão, apatia, psicose e agitação, frequentemente observadas em indivíduos com demência. Embora esses sintomas não sejam necessários para o diagnóstico da doença de Alzheimer, estão presentes em todas as fases ou estágios da doença, contribuindo negativamente para o declínio cognitivo, comprometimento funcional e sobrecarga do cuidador. Os sintomas neuropsiquiátricos têm sido conceituados não apenas como fatores de risco, mas também como marcadores clínicos de progressão da doença de Alzheimer. O construto "comprometimento comportamental leve", correlato comportamental do comprometimento cognitive leve, tem sido proposto nesse contexto. Os primeiros passos na abordagem dos sintomas comportamentais da doença de Alzheimer envolvem definir os alvos-terapêuticos e investigar potenciais causas ou fatores agravantes. Após intervir nesses fatores, abordagens não farmacológicas constituem a primeira linha de intervenção. Depois da otimização do tratamento anticolinesterásico, terapias farmacológicas específicas (por exemplo, antidepressivos, antipsicóticos) podem ser consideradas, levando-se em conta potencias efeitos colaterais.

Behavioral or neuropsychiatric symptoms of Alzheimer's disease: from psychopathology to pharmacological management / Sintomas comportamentais ou neuropsiquiátricos da doença de Alzheimer: psicopatologia e abordagem terapêutica

Abstract Neuropsychiatric or behavioral symptoms of dementia encompass a series of disorders, such as anxiety, depression, apathy, psychosis, and agitation, all commonly present in individuals living with dementia. While they are not required for the diagnosis of Alzheimer's disease (AD), they are ubiquitously present in all stages of the disease, contributing to negative clinical outcomes, including cognitive decline, functional disability, and caregiver burden. Neuropsychiatric symptoms have been conceptualized not only as risk factors but as clinical markers of decline along the AD spectrum. The concept of "mild behavioral impairment", the behavioral correlate of mild cognitive impairment, has been proposed within this framework. The first steps in the management of behavioral symptoms in AD involve defining the target and investigating potential causes and/or aggravating factors. Once these factors are addressed, non-pharmacological approaches are preferred as first-line interventions. Following the optimization of anticholinesterase treatments, specific pharmacological approaches (e.g., antidepressants, antipsychotics) can be considered weighing potential side effects.

Resumo Sintomas neuropsiquiátricos ou comportamentais de demência envolvem uma série de condições, como ansiedade, depressão, apatia, psicose e agitação, frequentemente observadas em indivíduos com demência. Embora esses sintomas não sejam necessários para o diagnóstico da doença de Alzheimer, estão presentes em todas as fases ou estágios da doença, contribuindo negativamente para o declínio cognitivo, comprometimento funcional e sobrecarga do cuidador. Os sintomas neuropsiquiátricos têm sido conceituados não apenas como fatores de risco, mas também como marcadores clínicos de progressão da doença de Alzheimer. O construto "comprometimento comportamental leve", correlato comportamental do comprometimento cognitive leve, tem sido proposto nesse contexto. Os primeiros passos na abordagem dos sintomas comportamentais da doença de Alzheimer envolvem definir os alvos-terapêuticos e investigar potenciais causas ou fatores agravantes. Após intervir nesses fatores, abordagens não farmacológicas constituem a primeira linha de intervenção. Depois da otimização do tratamento anticolinesterásico, terapias farmacológicas específicas (por exemplo, antidepressivos, antipsicóticos) podem ser consideradas, levando-se em conta potencias efeitos colaterais.

Potential Biomarkers of impulsivity in mild traumatic brain injury: A pilot study.

Very few studies have investigated cognition and impulsivity following mild traumatic brain injury (mTBI) in the general population. Furthermore, the neurobiological mechanisms underlying post-TBI neurobehavioral syndromes are complex and remain to be fully clarified. Herein, we took advantage of machine learning based-modeling to investigate potential biomarkers of mTBI-associated impulsivity. Twenty-one mTBI patients were assessed within one-month post-TBI and their data were compared to 19 healthy controls on measures of impulsivity (Barratt Impulsiveness Scale - BIS), executive functioning, episodic memory, self-report cognitive failures and blood biomarkers of inflammation, vascular and neuronal damage. mTBI patients were significantly more impulsive than controls in BIS total and subscales. Serum levels of sCD40L, Cathepsin D, IL-4, Neuropilin-1, IFN-α2, and Copeptin were associated with impulsivity in mTBI patients. Besides showing that mTBI are associated with impulsivity in non-military people, we unveiled different pathophysiological pathways potentially implicated in mTBI-related impulsivity.

Cognitive evaluation in Parkinson's disease: applying the Movement Disorder Society recommendations in a population with a low level of formal education.

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.

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.

Evaluation of New Potential Inflammatory Markers in Patients with Nonvalvular Atrial Fibrillation.

Atrial fibrillation (AF), the most common arrhythmia in clinical practice, is associated with an increase in mortality and morbidity due to its high potential to cause stroke and systemic thromboembolism. Inflammatory mechanisms may play a role in the pathogenesis of AF and its maintenance. We aimed to evaluate a range of inflammatory markers as potentially involved in the pathophysiology of individuals with nonvalvular AF (NVAF). A total of 105 subjects were enrolled and divided into two groups: patients with NVAF (n = 55, mean age 72 ± 8 years) and a control group of individuals in sinus rhythm (n = 50, mean age 71 ± 8 years). Inflammatory-related mediators were quantified in plasma samples by using Cytometric Bead Array and Multiplex immunoassay. Subjects with NVAF presented significantly elevated values of interleukin (IL)-2, IL-4, IL-6, IL-10, tumor necrosis factor (TNF), interferon-gamma, growth differentiation factor-15, myeloperoxidase, as well as IL-4, interferon-gamma-induced protein (IP-10), monokine induced by interferon-gamma, neutrophil gelatinase-associated lipocalin, and serum amyloid A in comparison with controls. However, after multivariate regression analysis adjusting for confounding factors, only IL-6, IL-10, TNF, and IP-10 remained significantly associated with AF. We provided a basis for the study of inflammatory markers whose association with AF has not been addressed before, such as IP-10, in addition to supporting evidence about molecules that had previously been associated with the disease. We expect to contribute to the discovery of markers that can be implemented in clinical practice hereafter.

Cognitive evaluation in Parkinson's disease: applying the Movement Disorder Society recommendations in a population with a low level of formal education / Avaliação cognitiva na doença de Parkinson: aplicando as recomendações da Movement Disorder Society em uma população de baixa escolaridade

Abstract 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.

Traumatic brain injury in Brazil: an epidemiological study and systematic review of the literature.

BACKGROUND: Traumatic brain injury (TBI) is a serious public health problem worldwide. Although TBI is common in developing countries, there are few epidemiological studies. OBJECTIVE: To investigate the sociodemographic and clinical features of patients with TBI at the Hospital João XXIII, a public reference center for trauma in Belo Horizonte, Brazil, and to systematically review the available literature on TBI in Brazil. METHODS: Clinical and sociodemographic data were collected from electronic medical records for the entire month of July 2016. The literature on epidemiology of TBI in Brazil was systematically reviewed using MeSH/DeCS descriptors in the PubMed and Lilacs databases. RESULTS: Most patients admitted with TBI were male and under 60 years of age. Mild TBI was the most prevalent form and the most common cause of TBI was falls. A Glasgow Coma Scale score below 12, neuroimaging changes on computer tomography, and presence of any medical conditions were significantly associated with longer hospital stay. Brazilian studies showed that TBI affected mainly men and young adults. In addition, mild TBI was the most common TBI severity reported and the most common causes were motor vehicle accidents and falls. CONCLUSIONS: Overall, the profile of TBI in this center reflects the data from other Brazilian studies.

Traumatic brain injury in Brazil: an epidemiological study and systematic review of the literature / Traumatismo cranioencefálico no Brasil: um estudo epidemiológico e uma revisão sistemática da literatura

ABSTRACT Background: Traumatic brain injury (TBI) is a serious public health problem worldwide. Although TBI is common in developing countries, there are few epidemiological studies. Objective: To investigate the sociodemographic and clinical features of patients with TBI at the Hospital João XXIII, a public reference center for trauma in Belo Horizonte, Brazil, and to systematically review the available literature on TBI in Brazil. Methods: Clinical and sociodemographic data were collected from electronic medical records for the entire month of July 2016. The literature on epidemiology of TBI in Brazil was systematically reviewed using MeSH/DeCS descriptors in the PubMed and Lilacs databases. Results: Most patients admitted with TBI were male and under 60 years of age. Mild TBI was the most prevalent form and the most common cause of TBI was falls. A Glasgow Coma Scale score below 12, neuroimaging changes on computer tomography, and presence of any medical conditions were significantly associated with longer hospital stay. Brazilian studies showed that TBI affected mainly men and young adults. In addition, mild TBI was the most common TBI severity reported and the most common causes were motor vehicle accidents and falls. Conclusions: Overall, the profile of TBI in this center reflects the data from other Brazilian studies.

RESUMO Antecedentes: O traumatismo cranioencefálico (TCE) representa, mundialmente, um problema sério de saúde pública. Apesar de o TCE ser prevalente em países em desenvolvimento, estudos epidemiológicos permanecem escassos. Objetivo: Investigar as características sociodemográficas e clínicas de pacientes acometidos por TCE no Hospital João XXIII - centro de referência em trauma situado em Belo Horizonte, Brasil - e revisar sistematicamente toda a literatura disponível sobre o TCE no Brasil. Métodos: Os dados clínicos e sociodemográficos foram coletados apenas para o mês de julho, 2016, por meio de prontuários eletrônicos. A literatura sobre a epidemiologia do TCE no Brasil foi sistematicamente revisada usando descritores Medical Subject Headings (MeSH)/Descritores em Ciências da Saúde (DeCS) nos bancos de dados PubMed e Literatura Latino-Americana e do Caribe em Ciências da Saúde (Lilacs). Resultados: Os pacientes acometidos por TCE eram em sua maioria homens com menos de 60 anos. O TCE leve foi a gravidade mais prevalente entre os casos. O TCE foi causado principalmente por quedas. Escores menores que 12 na escala de Coma de Glasgow mais alterações de neuroimagem em tomografia computadorizada e a presença de qualquer comorbidade médica estão significativamente associados à maior estadia hospitalar. Estudos brasileiros demonstraram que o TCE acomete principalmente homens e adultos jovens. Além disso, o TCE leve foi a gravidade mais comum reportada, e os mecanismos de TCE mais comuns foram acidentes automobilísticos e quedas. Conclusões: O perfil de pacientes acometidos por TCE no centro de referência em questão reflete os dados de outros estudos brasileiros.

Episodic memory for emotional and neutral pictures in Parkinson's disease.

OBJECTIVE: Prior studies have shown that individuals with Parkinson's disease (PD) exhibit deficits in the processing of emotional information. Here, we investigated whether such deficits caused by PD reduce the mnemonic benefits typically produced by emotion in healthy individuals. METHOD: Thirty individuals with PD and 30 healthy individuals, matched for sex, age, and education, were recruited for the study. To assess their memory for emotional information, we asked them to observe a series of negative, positive, and neutral images distributed in three consecutive blocks. After a short interval, all observed images were presented again intermixed with new images, and the participants were asked to judge whether each image was "old" or "new" (i.e., recognition test), and to indicate the block in which each image was studied (i.e., source memory test). In addition, to characterize the sample, all participants responded to a series of neuropsychological and psychopathological tests. RESULTS: As expected, individuals with PD exhibited diminished overall recognition and source memory scores relative to healthy controls (ηp² = 0.16 and 0.14, respectively). More importantly, while healthy controls showed greater recognition accuracy for negative versus neutral images (d = 0.65), this advantage was absent for PD participants (d < 0.18), a null effect corroborated by Bayesian analysis (BF01 = 3.34). CONCLUSION: The current findings suggest that individuals with PD lack the mnemonic advantage for negative pictures shown by healthy individuals, a deficit that may result from their difficulties in the processing of emotional information. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

Acute exercise increases BDNF serum levels in patients with Parkinson's disease regardless of depression or fatigue.

Studies have consistently reported a decreased level of brain-derived neurotrophic factor (BDNF) in individuals with Parkinson's disease (PD). The benefits of exercise on BDNF levels are well-documented in humans, however, the effects of acute exercise are inconclusive in neurological disorders. In addition, there are no studies investigating a precursor molecule - proBDNF - and its comparison to patients with vs. without depression or fatigue. Thirty patients with PD were instructed to walk on a treadmill at light to moderate intensity for 30 min. Generalized Estimating Equation (GEE) showed a significant effect of time (pre- vs. post-exercise) when compared individuals with vs. without depression [Wald Chi Square (4.392), p = 0.036)] and with vs. without fatigue [Wald Chi Square (7.123), p = 0.008)] for mature BDNF (mBDNF) level. There was no effect of group, time, and group x time interaction for proBDNF level when compared individuals with vs. without depression or fatigue. The present study showed that a single bout of light to moderate-intensity exercise increases mBDNF serum levels in patients with PD regardless of depression and fatigue. Our finding is important because it is necessary investigate methods to enhance the gains made by rehabilitation, especially when considering a short period of rehabilitation in different health services. The increase in mBDNF level can lead to an enhancement of neuroplasticity and facilitate the improvement of motor performance. No effect on proBDNF level could be explained, as this precursor molecule is cleaved by intracellular or extracellular enzymes.

IL-6 levels are associated with clinical status in patients with Myasthenia Gravis / Os níveis de IL-6 estão associados com o status clínico de pacientes com Miastenia Gravis

BACKGROUND: Myasthenia gravis (MG) is an autoimmune disease marked by fluctuating course of muscle weakness. OBJECTIVES: The current study was designed to evaluate plasma levels of cytokines (IL-2, IL-4, IL-6, IL-10, TNF, IFN-γ, and IL17A) in patients with MG and controls and to investigate whether cytokines levels are associated with clinical parameters. This study was conducted at the Neuromuscular Diseases Outpatient Clinic, Hospital das Clínicas, Universidade Federal de Minas Gerais (UFMG), Brazil. METHODS: Peripheral blood was drawn, and plasma levels of cytokines were measured by cytometric bead array (CBA) in 80 treated patients with MG and 50 controls. The MG Composite (MGC) was used to evaluate muscle weakness and severity of typical motor symptoms of MG. RESULTS: Patients with MG undergoing treatment exhibit lower levels of all evaluated cytokines compared to controls. There was a negative correlation between IL-6 levels and the MG Composite score, indicating that higher levels of IL-6 were associated with better control of the disease. CONCLUSION: This exploratory study suggests that IL-6 is associated with MG clinical status, as assessed by the MGC.

INTRODUÇÃO: A Miastenia Gravis (MG) é uma doença autoimune caracterizada por fraqueza muscular flutuante. OBJETIVOS: avaliar os níveis plasmáticos de citocinas (IL-2, IL-4, IL-6, IL-10, TNF, IFN-γ, e IL-17A) em pacientes com MG e controles e investigar se essas citocinas estão associadas com parâmetros clínicos. Este estudo foi conduzido no ambulatório de doenças neuromusculares do Hospital das Clínicas, Universidade Federal de Minas Gerais (UFMG), Brasil. MÉTODOS: Foi coletado sangue periféricos e os níveis plasmáticos das citocinas foram medidos por citometria em 80 pacientes com MG tratados e em 50 controles. O MG composite (MGC) foi utilizado para avaliar a fraqueza muscular e a gravidade dos sintomas motores típicos da MG. RESULTADOS: Os pacientes com MG em tratamento apresentaram menores níveis de todas as citocinas avaliadas comparados ao controle. Houve uma correlação negativa entre os níveis de IL-6 e o MGC, indicando que altos níveis de IL-6 estão associados com melhor controle da doença. CONCLUSÃO: este estudo exploratório sugere que a IL-6 está associada com o status clínico da MG, quando avaliado pelo MGC.

Clinical correlates of social cognition after an ischemic stroke: preliminary findings.

The co-occurrence of post-stroke behavioral disorders and cognitive impairment has been extensively investigated. However, studies usually do not include social cognition among the assessed cognitive domains. OBJECTIVE: To investigate the potential association between facial emotion recognition, a measure of social cognition, and behavioral and cognitive symptoms in the subacute phase of ischemic stroke. METHODS: Patients admitted to a Stroke Unit with ischemic stroke were followed up to 60 days. At this time point, they were evaluated with the following tools: Mini-Mental State Examination (MMSE); Frontal Assessment Battery (FAB); Visual Memory Test of the Brief Cognitive Battery (VMT); Phonemic Verbal Fluency (F-A-S Test); Digit Span; Facial Emotion Recognition Test (FERT) and Hospital Anxiety and Depression Scale (HADS). A control group composed of 21 healthy individuals also underwent the same evaluation. RESULTS: Eighteen patients with ischemic stroke were enrolled in this study. They had similar age, sex and schooling years compared to controls. Depression symptoms and episodic memory deficits were significantly more frequent in patients compared to controls. The recognition of sadness expression positively correlated with the levels of anxiety and depression, while and the recognition of fear expression negatively correlated with depression in the stroke group. CONCLUSIONS: After an ischemic stroke, patients exhibit impairment in social cognition skills, specifically facial emotion recognition, in association with behavioral symptoms.

A co-ocorrência de distúrbios comportamentais e comprometimento cognitivo pós-acidente vascular cerebral (AVC) é amplamente descrita na literatura. No entanto, os estudos geralmente não incluem a cognição social entre os domínios cognitivos avaliados. OBJETIVO: Investigar a potencial associação entre o reconhecimento da emoção facial, uma medida da cognição social, e os sintomas comportamentais e cognitivos na fase subaguda do AVC isquêmico. MÉTODOS: Pacientes internados em uma Unidade de AVC com AVC isquêmico foram acompanhados até 60 dias, quando foram avaliados com os seguintes instrumentos: Mini-Exame do Estado Mental (MEEM); Bateria de Avaliação Frontal (FAB); Teste de Memória Visual da Bateria Cognitiva Breve (VMT); Fluência Verbal Fonêmica (Teste F-A-S); Span de dígitos; Teste de Reconhecimento de Emoção Facial (FERT) e Escala Hospitalar de Ansiedade e Depressão (HADS). Um grupo controle constituído por 21 indivíduos saudáveis também foi submetido à mesma avaliação. RESULTADOS: Dezoito pacientes com AVC isquêmico foram incluídos no presente estudo, apresentando idade, sexo e anos de escolaridade semelhantes aos do grupo controle. Os sintomas de depressão e déficits de memória episódica foram significativamente mais frequentes em pacientes com AVC. O reconhecimento da expressão de tristeza correlacionou-se positivamente com os níveis de ansiedade e depressão, ao passo que o reconhecimento da expressão de medo correlacionou-se negativamente com depressão no grupo de AVC. CONCLUSÕES: Após um AVC isquêmico, pacientes podem apresentar alterações de cognição social, especificamente de reconhecimento da emoção facial, em associação com sintomas comportamentais.

Tumor necrosis factor superfamily molecules are increased in behavioral variant frontotemporal dementia and correlate with cortical atrophy: An exploratory investigation.

Frontotemporal dementia (FTD) is the second most frequent cause of young-onset dementia. Even though immune-mediated and neuroinflammatory factors have been recognized as potential pathophysiological mechanisms, the role of specific immune molecules, such as the tumor necrosis factor (TNF) superfamily, remains elusive. The aim of this study was to investigate TNF Superfamily Molecules (TNF, TNF-related weak inducer of apoptosis [TWEAK], soluble TNF receptor type 1 [sTNFRI] and soluble TNF receptor type 2 [sTNFRII]) in patients with behavioral variant FTD (bvFTD) and controls, and to explore potential associations with clinical parameters and brain atrophy. This study included two groups of participants matched for age, sex and schooling years: patients with probable bvFTD (n = 17, mean age = 64.9 years, 6 women/11 men) and healthy controls (HC, n = 17; mean age = 63.9 years, 10 women/7 men). All participants underwent comprehensive cognitive assessment and structural brain imaging with 3 T magnetic resonance imaging. Plasma levels of TNF, TWEAK, sTNFRI and sTNFRII were determined by ELISA. We conducted voxel-based morphometry analyses to investigate correlations between grey matter (GM) atrophy and plasma levels of TNF, TWEAK, sTNFRI and sTNFRII within bvFTD group. Compared to HC, bvFTD patients had lower cognitive scores and marked frontotemporal atrophy. Patients with bvFTD had significantly higher plasma levels of TNF (p < 0.0001), sTNFRI (p < 0.001), and sTNFRII (p < 0.0001), and similar levels of TWEAK in comparison with controls. The levels of sTNFRII were positively correlated with GM atrophy involving temporal poles, precuneus and cerebellum in bvFTD patients, while the levels of TWEAK positively correlated with right superior temporal gyrus. Our results implicate TNF superfamily in the pathophysiology of FTD.

Corrigendum to "Two protocols of aerobic exercise modulate the counter-regulatory axis of the renin-angiotensin system" [Heliyon 6 (1) (January 2020) e03208].

[This corrects the article DOI: 10.1016/j.heliyon.2020.e03208.].

Gene Expression Profiling in Huntington's Disease: Does Comorbidity with Depressive Symptoms Matter?

Huntington's disease (HD) is an inherited neurodegenerative disease. Besides the well-characterized motor symptoms, HD is marked by cognitive impairment and behavioral changes. In this study, we analyzed the blood of HD gene carries using RNA-sequencing techniques. We evaluated samples from HD gene carriers with (n = 8) and without clinically meaningful depressive symptoms (n = 8) compared with healthy controls (n = 8). Groups were age- and sex-matched. Preprocessing of data and between-group comparisons were calculated using DESeq2. The Wald test was used to generate p-values and log2 fold changes. We found 60 genes differently expressed in HD and healthy controls, of which 21 were upregulated and 39 downregulated. Within HD group, nineteen genes were differently expressed between patients with and without depression, being 6 upregulated and 13 downregulated. Several of the top differentially expressed genes are involved in nervous system development. Although preliminary, our findings corroborate the emerging view that in addition to neurodegenerative mechanisms, HD has a neurodevelopmental component. Importantly, the emergence of depression in HD might be related to these mechanisms.

ACE2 activator diminazene aceturate exerts renoprotective effects in gentamicin-induced acute renal injury in rats.

Acute Kidney Injury (AKI) comprises a rapidly developed renal failure and is associated with high mortality rates. The Renin-Angiotensin System (RAS) plays a pivotal role in AKI, as the over-active RAS axis exerts major deleterious effects in disease progression. In this sense, the conversion of Angiotensin II (Ang II) into Angiotensin-(1-7) (Ang-(1-7)) by the Angiotensin-converting enzyme 2 (ACE2) is of utmost importance to prevent worse clinical outcomes. Previous studies reported the beneficial effects of oral diminazene aceturate (DIZE) administration, an ACE2 activator, in renal diseases models. In the present study, we aimed to evaluate the therapeutic effects of DIZE administration in experimental AKI induced by gentamicin (GM) in rats. Our findings showed that treatment with DIZE improved renal function and tissue damage by increasing Ang-(1-7) and ACE2 activity, and reducing TNF-α. These results corroborate with a raising potential of ACE2 activation as a strategy for treating AKI.

Comparison of Inflammatory Mediators in Patients With Atrial Fibrillation Using Warfarin or Rivaroxaban.

Background: Atrial fibrillation (AF) is the most common arrhythmia associated with high risk of venous thromboembolism. Inflammatory mechanisms may be involved in the pathophysiology of AF and in the AF-related thrombogenesis, and patients with AF might benefit from the use of anticoagulants with anti-inflammatory properties. However, the evidence is still scarce, and it points out the need of trials seeking to investigate the levels of inflammatory mediators in patients with AF under different anticoagulant therapies. Therefore, this study was designed to define whether patients with AF treated either with an activated coagulation factor X (FXa) inhibitor (rivaroxaban) or with a vitamin K inhibitor (warfarin) present changes in peripheral levels of inflammatory mediators, mainly cytokines and chemokines. Methods: A total of 127 subjects were included in this study, divided into three groups: patients with non-valvular atrial fibrillation (NVAF) using warfarin (N = 42), patients with NVAF using rivaroxaban (N = 29), and controls (N = 56). Plasma levels of inflammatory mediators were quantified by immunoassays. Results: Patients with AF (both warfarin and rivaroxaban groups) presented increased levels of inflammatory cytokines in comparison with controls. The use of rivaroxaban was associated with decreased levels of inflammatory cytokines in comparison with warfarin. On the other hand, patients with AF using rivaroxaban presented increased levels of the chemokines (MCP-1 in comparison with warfarin users; MIG and IP-10 in comparison with controls). Conclusions: AF is associated with an inflammatory profile that was less pronounced in patients on rivaroxaban in comparison with warfarin users. Further studies are necessary to assess the clinical implications of our results and whether patients with AF would benefit from rivaroxaban anti-inflammatory effects.