How Mild Is the Mild Long COVID? A Comprehensive Neuropsychological Assessment of Patients with Cognitive Complaints.

The global impact of the Coronavirus Disease (COVID-19) pandemic has extended beyond physical health, leading to widespread mental health issues. Beyond respiratory symptoms, there is a growing concern about long-term cognitive effects, particularly in individuals who experienced mild cases of the infection. We aimed to investigate the neuropsychological aspects of long-term COVID-19 in non-hospitalized adults compared with a control group. This cross-sectional study included 42 participants, 22 individuals with a history of mild COVID, and 20 healthy controls. The participants were recruited from the community and underwent a comprehensive neuropsychological assessment. Participants from the mild COVID group reported cognitive symptoms persisting for an average of 203.86 days and presented a higher frequency of psychological treatment history (81.8%) compared with the control group (25.0%). History of anxiety disorders was more prevalent in the mild COVID group (63.6%) than in the control group (20.0%). Significant reductions in verbal working memory were observed in the mild COVID group. Levels of anxiety were found to have a significant impact on difficulties with visual recognition memory. This study reveals important neuropsychological alterations in individuals following mild COVID-19, emphasizing executive functions deficits. Our findings underscore the persistence of these deficits even in non-hospitalized cases, suggesting potential inflammatory mechanisms in the central nervous system. The study highlights the need for comprehensive assessments and targeted interventions to address the diverse cognitive impacts on individuals recovering from COVID-19.

Cortisol and cortisone determination by disposable pipette extraction (DPX) and ultra-efficient liquid chromatography tandem mass spectrometry (UHPLC-MS/MS) in urine and saliva samples from patients with Parkinson's disease.

Higher serum cortisol levels appear to be associated with stress that can overlap or manifest anxiety, fatigue, depression, and sleep dysfunction. These are common and intrusive non-motor symptoms of Parkinson's disease (PD). Thus, stress has been proposed to mediate Parkinson's disease development, and cortisol has been suggested as a biomarker for the generation of stress-related symptoms in Parkinson's disease. This study describes sensitive and robust disposable pipette extraction (DPX) and ultra-efficient liquid chromatography tandem mass spectrometry (UHPLC-MS/MS) method to determine cortisol and cortisone (as potential endocrine biomarkers for Parkinson's disease) in 24-h urine and saliva samples obtained from Parkinson's disease patients. Important parameters on DPX extraction were optimized to achieve the best extraction recovery and cleanup efficiency. The proposed method was linear from 0.5 (lower limit of quantification) to 500 ng mL-1 for cortisol and from 3.0 (lower limit of quantification) to 500 ng mL-1 for cortisone. To determine whether urinary cortisol and urinary cortisone are adequate as biomarkers to evaluate the level of anxiety in patients suffering from Parkinson's disease, twenty-nine Parkinson's disease patients (18 with anxiety and 11 without anxiety) were selected for urine analysis. Based on the obtained results, 24-h urine samples obtained from Parkinson's disease patients with anxiety had higher cortisone levels than samples obtained from healthy controls. Receiving operating curves (ROC) analysis, which presented the area under the ROC curve (AUC = 0.733), showed that urinary cortisone levels (µg/24-h urine) were sensitive (56.3%) and specific (93.3%) for distinguishing Parkinson's disease patients with anxiety from healthy controls. In terms of salivary results, PD patients' samples taken 30 min after waking up had higher cortisol and cortisone levels than healthy controls, while their samples taken at night had lower cortisol and cortisone levels.

Parkinson's disease and levodopa-induced dyskinesias: a quantitative analysis through 99mTc-TRODAT-1 SPECT imaging of the brain.

Objective: To compare the dopamine transporter (DAT) density with other risk factors for L-DOPA-induced dyskinesia (LID) in patients with Parkinson's disease (PD), with and without LID. Materials and Methods: We evaluated 67 subjects: 44 patients with idiopathic PD of varying degrees of severity (PD group), and 23 healthy age-matched volunteers (control group). Among the 44 patients in the PD group, 29 were male and the following means were recorded at baseline: age, 59 ± 7 years; disease duration, 10 ± 6 years; Hoehn and Yahr (H&Y) stage, 2.16 ± 0.65; and Unified Parkinson's Disease Rating Scale part III (UPDRS III) score, 29.74 ± 17.79. All subjects underwent 99mTc-TRODAT-1 SPECT. We also calculated specific uptake ratios or binding potentials in the striatum. Results: The DAT density in the ipsilateral and contralateral striata was lower in the PD group. The variables disease duration, L-DOPA dosage, doses per day, L-DOPA effect duration time, H&Y stage, and UPDRS III score explained the occurrence of LID. The DAT density in the ipsilateral striatum, contralateral striatum, and caudate nucleus was lower in the patients with LID than in those without. Conclusion: Our findings suggest that presynaptic dopaminergic denervation is associated with LID in individuals with PD.

Objetivo: Comparar a densidade do transportador de dopamina (DAT) com outros fatores de risco para discinesia induzida pela L-DOPA em pacientes com doença de Parkinson, com e sem discinesias. Materiais e Métodos: Sessenta e sete sujeitos, 23 voluntários saudáveis e 44 pacientes pareados por idade com diferentes graus de gravidade da doença de Parkinson idiopática (29 homens; idade média ± desvio-padrão (DP), 59 ± 7 anos; duração média ± DP dos sintomas, 10 ± 6 anos; H&Y: média ± DP, 2,16 ± 0,65; UPDRS III: média ± DP, 29,74 ± 17,79). Todos os sujeitos realizaram SPECT cerebral com 99mTc-TRODAT-1. Além disso, foram calculadas as taxas de captação específica ou potenciais de ligação no estriado. Resultados: A densidade de DAT do estriado ipsilateral ou contralateral foi menor no grupo doença de Parkinson. As variáveis duração da doença, dosagem de L-DOPA, doses por dia, tempo de duração do efeito da L-DOPA, H&Y e UPDRS III explicaram a ocorrência de discinesia. Adicionalmente, pacientes com discinesia exibiram menor densidade de DAT no estriado ipsilateral ou contralateral e no núcleo caudado do que os pacientes sem discinesia. Conclusão: O presente estudo sugere que a denervação dopaminérgica pré-sináptica na doença de Parkinson está associada ao desenvolvimento de discinesia induzida pela L-DOPA.

The clinical diagnosis of Parkinson's disease.

After more than 200 years since its initial description, the clinical diagnosis of Parkinson's disease (PD) remains an often-challenging endeavor, with broad implications that are fundamental for clinical management. Despite major developments in understanding it's pathogenesis, pathological landmarks, non-motor features and potential paraclinical clues, the most accepted diagnostic criteria remain solidly based on a combination of clinical signs. Here, we review this process, discussing its history, clinical criteria, differential diagnoses, ancillary diagnostic testing, and the role of non-motor and pre-motor signs and symptoms.

Passados mais de 200 anos desde a sua descrição inicial, o diagnóstico clínico da doença de Parkinson (DP) continua a ser um processo muitas vezes desafiante, com amplas implicações que são fundamentais para o manejo clínico. Apesar dos grandes desenvolvimentos na compreensão da sua patogénese, marcadores patológicos, características não motoras e potenciais pistas paraclínicas, os critérios diagnósticos mais aceitos permanecem solidamente baseados numa combinação de sinais clínicos motores. Aqui, revisamos esse processo, discutindo sua história, critérios clínicos, diagnósticos diferenciais, testes diagnósticos complementares e o papel dos sinais e sintomas não motores e pré-motores.

Genetic Epidemiology and Clinical Characteristics of Patients with Spinocerebellar Ataxias in an Unexplored Brazilian State, Using Strategies for Resource-Limited Settings.

Spinocerebellar ataxias (SCAs) have a worldwide average prevalence of 2.7 cases per 100,000 individuals, with significant geographic variability. This study aimed to develop resource-limited strategies to detect and characterize the frequency and genetic-clinical profile of SCAs in an unexplored population from Alagoas State, a low Human Development Index state in northeastern Brazil. Active search strategies were employed to identify individuals with a diagnosis or clinical suspicion of SCAs, and a protocol for clinical and molecular evaluation was applied in collaboration with a reference center in Neurogenetics. A total of 73 individuals with SCAs were identified, with a minimum estimated prevalence of 2.17 cases per 100,000 inhabitants. SCA3 was the most common type (75.3%), followed by SCA7 (15.1%), SCA1 (6.8%), and SCA2 (2.7%). Patients with SCA3 subphenotype 2 were the most predominant. Detailed analysis of patients with SCA3 and SCA7 revealed age at onset and clinical features congruent with other studies, with gait disturbance and reduced visual capacity in SCA7 as the main initial manifestations. The study also identified many asymptomatic individuals at risk of developing SCAs. These findings demonstrate that simple and collaborative strategies can enhance the detection capacity of rare diseases such as SCAs in resource-limited settings and that Alagoas State has a minimum estimated prevalence of SCAs similar to the world average.

The clinical diagnosis of Parkinson's disease / O diagnóstico clínico da doença de Parkinson

Abstract After more than 200 years since its initial description, the clinical diagnosis of Parkinson's disease (PD) remains an often-challenging endeavor, with broad implications that are fundamental for clinical management. Despite major developments in understanding it's pathogenesis, pathological landmarks, non-motor features and potential paraclinical clues, the most accepted diagnostic criteria remain solidly based on a combination of clinical signs. Here, we review this process, discussing its history, clinical criteria, differential diagnoses, ancillary diagnostic testing, and the role of non-motor and pre-motor signs and symptoms.

Resumo Passados mais de 200 anos desde a sua descrição inicial, o diagnóstico clínico da doença de Parkinson (DP) continua a ser um processo muitas vezes desafiante, com amplas implicações que são fundamentais para o manejo clínico. Apesar dos grandes desenvolvimentos na compreensão da sua patogénese, marcadores patológicos, características não motoras e potenciais pistas paraclínicas, os critérios diagnósticos mais aceitos permanecem solidamente baseados numa combinação de sinais clínicos motores. Aqui, revisamos esse processo, discutindo sua história, critérios clínicos, diagnósticos diferenciais, testes diagnósticos complementares e o papel dos sinais e sintomas não motores e pré-motores.

Parkinson's disease and levodopa-induced dyskinesias: a quantitative analysis through 99mTc-TRODAT-1 SPECT imaging of the brain / Doença de Parkinson e discinesias induzidas por levodopa: uma análise quantitativa por meio de imagem cerebral com SPECT 99mTc-TRODAT-1

Abstract Objective: To compare the dopamine transporter (DAT) density with other risk factors for L-DOPA-induced dyskinesia (LID) in patients with Parkinson's disease (PD), with and without LID. Materials and Methods: We evaluated 67 subjects: 44 patients with idiopathic PD of varying degrees of severity (PD group), and 23 healthy age-matched volunteers (control group). Among the 44 patients in the PD group, 29 were male and the following means were recorded at baseline: age, 59 ± 7 years; disease duration, 10 ± 6 years; Hoehn and Yahr (H&Y) stage, 2.16 ± 0.65; and Unified Parkinson's Disease Rating Scale part III (UPDRS III) score, 29.74 ± 17.79. All subjects underwent 99mTc-TRODAT-1 SPECT. We also calculated specific uptake ratios or binding potentials in the striatum. Results: The DAT density in the ipsilateral and contralateral striata was lower in the PD group. The variables disease duration, L-DOPA dosage, doses per day, L-DOPA effect duration time, H&Y stage, and UPDRS III score explained the occurrence of LID. The DAT density in the ipsilateral striatum, contralateral striatum, and caudate nucleus was lower in the patients with LID than in those without. Conclusion: Our findings suggest that presynaptic dopaminergic denervation is associated with LID in individuals with PD.

Resumo Objetivo: Comparar a densidade do transportador de dopamina (DAT) com outros fatores de risco para discinesia induzida pela L-DOPA em pacientes com doença de Parkinson, com e sem discinesias. Materiais e Métodos: Sessenta e sete sujeitos, 23 voluntários saudáveis e 44 pacientes pareados por idade com diferentes graus de gravidade da doença de Parkinson idiopática (29 homens; idade média ± desvio-padrão (DP), 59 ± 7 anos; duração média ± DP dos sintomas, 10 ± 6 anos; H&Y: média ± DP, 2,16 ± 0,65; UPDRS III: média ± DP, 29,74 ± 17,79). Todos os sujeitos realizaram SPECT cerebral com 99mTc-TRODAT-1. Além disso, foram calculadas as taxas de captação específica ou potenciais de ligação no estriado. Resultados: A densidade de DAT do estriado ipsilateral ou contralateral foi menor no grupo doença de Parkinson. As variáveis duração da doença, dosagem de L-DOPA, doses por dia, tempo de duração do efeito da L-DOPA, H&Y e UPDRS III explicaram a ocorrência de discinesia. Adicionalmente, pacientes com discinesia exibiram menor densidade de DAT no estriado ipsilateral ou contralateral e no núcleo caudado do que os pacientes sem discinesia. Conclusão: O presente estudo sugere que a denervação dopaminérgica pré-sináptica na doença de Parkinson está associada ao desenvolvimento de discinesia induzida pela L-DOPA.

Floor and ceiling effects on the Montreal Cognitive Assessment in patients with Parkinson's disease in Brazil.

Parkinson's disease (PD) is a common neurodegenerative disease associated with cognitive impairment. The Montreal Cognitive Assessment (MoCA) has been used as a recommended global cognition scale for patients with PD, but there are some concerns about its application, partially due to the floor and ceiling effects. Objective: To explore the floor and ceiling effects on the MoCA in patients with PD in Brazil. Methods: Cross-sectional study with data from patients with PD from five Brazilian Movement Disorders Clinics, excluding individuals with a possible diagnosis of dementia. We analyzed the total score of the MoCA, as well as its seven cognitive domains. The floor and ceiling effects were evaluated for the total MoCA score and domains. Multivariate analyses were performed to detect factors associated with floor and ceiling effects. Results: We evaluated data from 366 patients with PD and approximately 19% of individuals had less than five years of education. For the total MoCA score, there was no floor or ceiling effect. There was a floor effect in the abstraction and delayed memory recall domains in 20% of our sample. The ceiling effect was demonstrated in all domains (80.8% more common in naming and 89% orientation), except delayed recall. Education was the main factor associated with the floor and ceiling effects, independent of region, sex, age at evaluation, and disease duration. Conclusion: The floor and ceiling effects are present in specific domains of the MoCA in Brazil, with a strong impact on education. Further adaptations of the MoCA structure for underrepresented populations may reduce these negative effects.

A doença de Parkinson (DP) é uma doença neurodegenerativa comum associada ao declínio cognitivo. A Avaliação Cognitiva de Montreal (Montreal Cognitive Assessment ­ MoCA) tem sido usada como uma escala de cognição global recomendada para pacientes com DP, mas existem algumas preocupações sobre sua aplicação, em parte pelos efeitos solo e teto. Objetivo: Explorar os efeitos solo e teto na MoCA em pacientes com DP no Brasil. Métodos: Estudo transversal com dados de pacientes com DP oriundos de cinco Clínicas de Distúrbios de Movimento no Brasil, excluindo-se pessoas com possível diagnóstico de demência. Nós analisamos a pontuação total da MoCA, assim como a de seus sete domínios cognitivos. Os efeitos solo e teto foram avaliados para a pontuação total da MoCA e seus domínios. Foram feitas análises multivariadas para a detecção de fatores associados os efeitos solo e teto. Resultados: Nós avaliamos dados de 366 pacientes com DP, e aproximadamente 19% das pessoas tinham menos que cinco anos de escolaridade. Para a pontuação total do MoCA, não houve efeito solo ou teto. Houve efeito solo nos domínios abstração e memória de evocação tardia em 20% de nossa amostra. O efeito teto foi demonstrado em todos os domínios (80,8% mais comum em nomeação e 89% orientação), com exceção de memória de evocação tardia. A educação foi o principal fator associado aos efeitos solo e teto, independentemente de região, sexo, idade na avaliação e duração da doença. Conclusão: Os efeitos solo e teto estão presentes em domínios específicos da MoCA no Brasil, com forte impacto da educação. Adaptações adicionais à estrutura da MoCA para populações vulneráveis podem reduzir esses efeitos negativos.

Movement disorders in hereditary spastic paraplegias.

BACKGROUND: Hereditary or familial spastic paraplegias (SPG) comprise a group of genetically and phenotypically heterogeneous diseases characterized by progressive degeneration of the corticospinal tracts. The complicated forms evolve with other various neurological signs and symptoms, including movement disorders and ataxia. OBJECTIVE: To summarize the clinical descriptions of SPG that manifest with movement disorders or ataxias to assist the clinician in the task of diagnosing these diseases. METHODS: We conducted a narrative review of the literature, including case reports, case series, review articles and observational studies published in English until December 2022. RESULTS: Juvenile or early-onset parkinsonism with variable levodopa-responsiveness have been reported, mainly in SPG7 and SPG11. Dystonia can be observed in patients with SPG7, SPG11, SPG22, SPG26, SPG35, SPG48, SPG49, SPG58, SPG64 and SPG76. Tremor is not a frequent finding in patients with SPG, but it is described in different types of SPG, including SPG7, SPG9, SPG11, SPG15, and SPG76. Myoclonus is rarely described in SPG, affecting patients with SPG4, SPG7, SPG35, SPG48, and SPOAN (spastic paraplegia, optic atrophy, and neuropathy). SPG4, SPG6, SPG10, SPG27, SPG30 and SPG31 may rarely present with ataxia with cerebellar atrophy. And autosomal recessive SPG such as SPG7 and SPG11 can also present with ataxia. CONCLUSION: Patients with SPG may present with different forms of movement disorders such as parkinsonism, dystonia, tremor, myoclonus and ataxia. The specific movement disorder in the clinical manifestation of a patient with SPG may be a clinical clue for the diagnosis.

ANTECEDENTES: As paraplegias espásticas hereditárias ou familiares (SPG) compreendem um grupo de doenças geneticamente e fenotipicamente heterogêneas caracterizadas por degeneração progressiva dos tratos corticospinais. As formas complicadas evoluem com vários outros sinais e sintomas neurológicos, incluindo distúrbios do movimento e ataxia. OBJETIVO: Resumir as descrições clínicas de SPG que se manifestam com distúrbios do movimento ou ataxias para auxiliar o clínico na tarefa de diagnosticar essas doenças. MéTODOS: Realizamos uma revisão da literatura, incluindo relatos de casos, séries de casos, artigos de revisão e estudos observacionais publicados em inglês até dezembro de 2022. RESULTADOS: O parkinsonismo juvenil ou de início precoce com resposta variável à levodopa foi relatado principalmente em SPG7 e SPG11. A distonia pode ser observada em pacientes com SPG7, SPG11, SPG22, SPG26, SPG35, SPG48, SPG49, SPG58, SPG64 e SPG76. O tremor não é um achado frequente em pacientes com SPG, mas é descrito em diferentes tipos de SPG, incluindo SPG7, SPG9, SPG11, SPG15 e SPG76. A mioclonia é raramente descrita em SPG, afetando pacientes com SPG4, SPG7, SPG35, SPG48 e SPOAN (paraplegia espástica, atrofia óptica e neuropatia). SPG4, SPG6, SPG10, SPG27, SPG30 e SPG31 podem raramente apresentar ataxia com atrofia cerebelar. E SPG autossômico recessivo, como SPG7 e SPG11, também pode apresentar ataxia. CONCLUSãO: Indivíduos com SPG podem apresentar diferentes formas de distúrbios do movimento, como parkinsonismo, distonia, tremor, mioclonia e ataxia. O distúrbio específico do movimento na manifestação clínica de um paciente com SPG pode ser uma pista clínica para o diagnóstico.

Average annual cost of Parkinson's disease in a Brazilian multiethnic population.

INTRODUCTION: With the current demographic transition, it is estimated that by 2050 Brazil will have a population of 90 million people aged 60 years or more, and in parallel Parkinson's disease (PD) will bring a considerable economic burden to our society. Brazil is considered multiracial due to its colonization, generating important social and regional inequalities. Knowing the costs of the PD may aid to improve local public policies. However, in Brazil, no estimates of these values have been made so far. OBJECTIVES: To evaluate direct, indirect, and out-of-pocket costs in Brazilian people with PD (PwP). METHODS: Categorical and numerical data were collected through a customized and standardized cost-related-questionnaire from 1055 PwP nationwide, from 10 tertiary movement disorders centers across all Brazilian regions. RESULTS: The estimated average annual cost of PwP was US$ 4020.48. Direct and indirect costs accounted for 63% and 36% of the total, respectively, and out-of-pocket costs were 49%. There were no evidence of differences in the total cost of PD across the regions of the country; however, differences were reported between the stages of the Hoehn and Yahr scale (H&Y). CONCLUSION: This data suggests a considerable burden of PD for Brazilian society in general, not only for the public health system, but mainly for those with PD.

Movement disorders in hereditary spastic paraplegias / Distúrbios de movimento em paraplegia espástica hereditária

Abstract Background Hereditary or familial spastic paraplegias (SPG) comprise a group of genetically and phenotypically heterogeneous diseases characterized by progressive degeneration of the corticospinal tracts. The complicated forms evolve with other various neurological signs and symptoms, including movement disorders and ataxia. Objective To summarize the clinical descriptions of SPG that manifest with movement disorders or ataxias to assist the clinician in the task of diagnosing these diseases. Methods We conducted a narrative review of the literature, including case reports, case series, review articles and observational studies published in English until December 2022. Results Juvenile or early-onset parkinsonism with variable levodopa-responsiveness have been reported, mainly in SPG7 and SPG11. Dystonia can be observed in patients with SPG7, SPG11, SPG22, SPG26, SPG35, SPG48, SPG49, SPG58, SPG64 and SPG76. Tremor is not a frequent finding in patients with SPG, but it is described in different types of SPG, including SPG7, SPG9, SPG11, SPG15, and SPG76. Myoclonus is rarely described in SPG, affecting patients with SPG4, SPG7, SPG35, SPG48, and SPOAN (spastic paraplegia, optic atrophy, and neuropathy). SPG4, SPG6, SPG10, SPG27, SPG30 and SPG31 may rarely present with ataxia with cerebellar atrophy. And autosomal recessive SPG such as SPG7 and SPG11 can also present with ataxia. Conclusion Patients with SPG may present with different forms of movement disorders such as parkinsonism, dystonia, tremor, myoclonus and ataxia. The specific movement disorder in the clinical manifestation of a patient with SPG may be a clinical clue for the diagnosis.

Resumo Antecedentes As paraplegias espásticas hereditárias ou familiares (SPG) compreendem um grupo de doenças geneticamente e fenotipicamente heterogêneas caracterizadas por degeneração progressiva dos tratos corticospinais. As formas complicadas evoluem com vários outros sinais e sintomas neurológicos, incluindo distúrbios do movimento e ataxia. Objetivo Resumir as descrições clínicas de SPG que se manifestam com distúrbios do movimento ou ataxias para auxiliar o clínico na tarefa de diagnosticar essas doenças. Métodos Realizamos uma revisão da literatura, incluindo relatos de casos, séries de casos, artigos de revisão e estudos observacionais publicados em inglês até dezembro de 2022. Resultados O parkinsonismo juvenil ou de início precoce com resposta variável à levodopa foi relatado principalmente em SPG7 e SPG11. A distonia pode ser observada em pacientes com SPG7, SPG11, SPG22, SPG26, SPG35, SPG48, SPG49, SPG58, SPG64 e SPG76. O tremor não é um achado frequente em pacientes com SPG, mas é descrito em diferentes tipos de SPG, incluindo SPG7, SPG9, SPG11, SPG15 e SPG76. A mioclonia é raramente descrita em SPG, afetando pacientes com SPG4, SPG7, SPG35, SPG48 e SPOAN (paraplegia espástica, atrofia óptica e neuropatia). SPG4, SPG6, SPG10, SPG27, SPG30 e SPG31 podem raramente apresentar ataxia com atrofia cerebelar. E SPG autossômico recessivo, como SPG7 e SPG11, também pode apresentar ataxia. Conclusão Indivíduos com SPG podem apresentar diferentes formas de distúrbios do movimento, como parkinsonismo, distonia, tremor, mioclonia e ataxia. O distúrbio específico do movimento na manifestação clínica de um paciente com SPG pode ser uma pista clínica para o diagnóstico.

Hearts and Minds: Emotion Recognition and Mentalizing in Parkinson's Disease and Progressive Supranuclear Palsy.

OBJECTIVE: There are scarce data comparing Parkinson's disease (PD) and Progressive Supranuclear Palsy (PSP) in social cognition (SC). We aimed to compare patients with PSP and PD in SC. METHODS: We included three groups: PD (n = 18), PSP (n = 20) and controls (n = 23). Participants underwent neuropsychological exams, including the mini-version of the Social and Emotional Assessment, which is composed of the facial emotion recognition test (FERT) and the modified faux-pas (mFP) test, which assesses Theory of Mind (ToM). RESULTS: Patients with PD scored lower than controls in the FERT, but not in the mFP test. Patients with PSP performed worse than controls in both the mFP and FERT. PD and PSP groups did not differ in the FERT, but PSP performed worse than PD in the mFP test. The mFP test distinguished PSP from PD with 89% accuracy. CONCLUSION: The assessment of ToM may contribute to the differentiation between PD and PSP.

History of high household pesticide use and Parkinson's disease in Brazil.

The prevalence of Parkinson's disease (PD) is growing worldwide and household pesticides exposure may be related to this phenomenon. We showed that individuals with high exposure to household pesticides have two times more risk of developing PD. Household pesticide exposure did not impact age at PD onset.

Doxycycline to treat levodopa-induced dyskinesias in Parkinson's disease: a preliminary study.

BACKGROUND: Levodopa-induced dyskinesia (LID) is a common motor complication of levodopa therapy in patients with Parkinson's disease (PD). Doxycycline is a widely used and inexpensive tetracycline with anti-inflammatory properties. OBJECTIVE: To evaluate the efficacy and safety of doxycycline in patients with PD and LID. METHODS: This was an open-label, uncontrolled, single-arm, single-center, phase 2 proof-of-concept study in patients with PD with functional impact of dyskinesia, which used levodopa three times daily, in a movement disorders clinic in Brazil. Participants were treated with doxycycline 200 mg/day for 12 weeks, with evaluations at baseline, week 4, and week 12 of treatment. The primary outcome measure was the change from baseline in the Unified Dyskinesia Rating Scale (UDysRS) total score at week 12, evaluated by two blinded raters. Key secondary outcomes measures were OFF time and ON time with troublesome dyskinesia in the PD home diary. RESULTS: Eight patients with PD were treated and evaluated. Doxycycline 200 mg/day reduced the UDysRS total score at week 12, compared with baseline (Friedman χ2 = 9.6; p = 0.008). Further, doxycycline reduced the ON time with troublesome dyskinesia (Friedman χ2 = 10.8; p = 0.004) without worsening parkinsonism. There were no severe adverse events, and dyspepsia was the commonest event. CONCLUSION: In this preliminary, open-label and uncontrolled trial, doxycycline was effective in reducing LID and safe after a 12-week treatment. Further well-designed placebo-controlled clinical trials with a longer duration and a larger number of participants are needed. CLINICAL TRIAL REGISTRATION: https://ensaiosclinicos.gov.br, identifier: RBR-1047fwbf.

ANTECEDENTES: A discinesia induzida por levodopa (DIL) é uma complicação motora comum da terapia com levodopa em pacientes com doença de Parkinson (DP). A doxiciclina é uma tetraciclina amplamente usada e barata, com propriedade anti-inflamatória. OBJETIVO: Avaliar a eficácia e segurança da doxiciclina em pacientes com DP e DIL. MéTODOS: Este foi um estudo aberto, não-controlado, de braço único, monocêntrico, fase 2 e de prova de conceito, em pacientes com DP e impacto funcional das discinesias, que usavam levodopa três vezes ao dia, em um ambulatório de distúrbios de movimento no Brasil. Os participantes foram tratados com doxiciclina 200 mg/dia por 12 semanas, com avaliações na base, na semana 4 e na semana 12 do tratamento. A medida de desfecho primário foi a mudança no escore total da Unified Dyskinesia Rating Scale (UDysRS) da base à semana 12, avaliada por dois avaliadores cegos. As medidas-chave de desfecho secundário fora o tempo em OFF e tempo em ON com discinesia problemática. RESULTADOS: Oito pacientes com DP foram tratados e avaliados. A doxiciclina 200 mg/dia reduziu o escore total da UDysRS na semana 12, comparado com a avaliação inicial (χ2 de Friedman = 9.6; p = 0.008). Além disso, a doxiciclina reduziu o tempo em ON com discinesia problemática (χ2 de Friedman = 10.8; p = 0.004) sem piorar o parkinsonismo. Não houve eventos adversos graves, e dispepsia foi o evento mais comum. CONCLUSãO: No presente estudo preliminar, aberto e não-controlado, a doxiciclina foi eficaz em reduzir as DIL e segura após tratamento por 12 semanas. Estudos clínicos bem-desenhados e placebo-controlados adicionais, com duração mais longa e maior número de participantes, são necessários.

Doxycycline to treat levodopa-induced dyskinesias in Parkinson's disease: a preliminary study / Doxiciclina no tratamento das discinesias induzidas pela doença de Parkinson: um estudo preliminar

Abstract Background Levodopa-induced dyskinesia (LID) is a common motor complication of levodopa therapy in patients with Parkinson's disease (PD). Doxycycline is a widely used and inexpensive tetracycline with anti-inflammatory properties. Objective To evaluate the efficacy and safety of doxycycline in patients with PD and LID. Methods This was an open-label, uncontrolled, single-arm, single-center, phase 2 proof-of-concept study in patients with PD with functional impact of dyskinesia, which used levodopa three times daily, in a movement disorders clinic in Brazil. Participants were treated with doxycycline 200 mg/day for 12 weeks, with evaluations at baseline, week4, and week 12 of treatment. The primary outcome measure was the change from baseline in the Unified Dyskinesia Rating Scale (UDysRS) total score at week 12, evaluated by two blinded raters. Key secondary outcomes measures were OFF time and ON time with troublesome dyskinesia in the PD home diary. Results Eight patients with PD were treated and evaluated. Doxycycline 200 mg/day reduced the UDysRS total score at week 12, compared with baseline (Friedman χ2 = 9.6; p = 0.008). Further, doxycycline reduced the ON time with troublesome dyskinesia (Friedman χ2 = 10.8; p = 0.004) without worsening parkinsonism. There were no severe adverse events, and dyspepsia was the commonest event. Conclusion In this preliminary, open-label and uncontrolled trial, doxycycline was effective in reducing LID and safe after a 12-week treatment. Further well-designed placebo-controlled clinical trials with a longer duration and a larger number of participants are needed. Clinical trial registration https://ensaiosclinicos.gov.br, identifier: RBR-1047fwbf

Resumo Antecedentes A discinesia induzida por levodopa (DIL) é uma complicação motora comum da terapia com levodopa em pacientes com doença de Parkinson (DP). A doxiciclina é uma tetraciclina amplamente usada e barata, com propriedade anti-inflamatória. Objetivo Avaliar a eficácia e segurança da doxiciclina em pacientes com DP e DIL. Métodos Este foi um estudo aberto, não-controlado, de braço único, monocêntrico, fase 2 e de prova de conceito, em pacientes com DP e impacto funcional das discinesias, que usavam levodopa três vezes ao dia, em um ambulatório de distúrbios de movimento no Brasil. Os participantes foram tratados com doxiciclina 200 mg/dia por 12 semanas, com avaliações na base, na semana 4 e na semana 12 do tratamento. A medida de desfecho primário foi a mudança no escore total da Unified Dyskinesia Rating Scale (UDysRS) da base à semana 12, avaliada por dois avaliadores cegos. As medidas-chave de desfecho secundário fora o tempo em OFF e tempo em ON com discinesia problemática. Resultados Oito pacientes com DP foram tratados e avaliados. A doxiciclina 200 mg/dia reduziu o escore total da UDysRS na semana 12, comparado com a avaliação inicial (χ2 de Friedman = 9.6; p = 0.008). Além disso, a doxiciclina reduziu o tempo em ON com discinesia problemática (χ2 de Friedman = 10.8; p = 0.004) sem piorar o parkinsonismo. Não houve eventos adversos graves, e dispepsia foi o evento mais comum. Conclusão No presente estudo preliminar, aberto e não-controlado, a doxiciclina foi eficaz em reduzir as DIL e segura após tratamento por 12 semanas. Estudos clínicos bem-desenhados e placebo-controlados adicionais, com duração mais longa e maior número de participantes, são necessários.

Direct coupling of fiber-in-tube solid-phase microextraction with tandem mass spectrometry to determine amyloid beta peptides as biomarkers for Alzheimer's disease in cerebrospinal fluid samples.

Current research efforts at neurological diseases have focused on identifying novel biomarkers to aid in diagnosis, to provide accurate prognostic information, and to monitor disease progression. This study presents the direct coupling of fiber-in-tube solid-phase microextraction to tandem mass spectrometry as a reliable method to determine amyloid beta peptides (Aß38, Aß40, and Aß42) as biomarkers for Alzheimer's disease in cerebrospinal fluid (CSF) samples. To obtain the biocompatible fiber-in-tube SPME capillary, a PEEK tube segment was longitudinally packed with fine fibers [nitinol wires coated with a zwitterionic polymeric ionic liquid], to act as selective extraction medium. The fiber-in-tube SPME-MS/MS method integrated analyte extraction/enrichment and sample cleanup (exclusion of interferents) into one step. The method provided lower limits of quantification (LLOQ: 0.2 ng mL-1 for Aß38 and 0.1 ng mL-1 for Aß40 and Aß42), high precision (CV lower than 11.6%), and high accuracy (relative standard deviation lower than 15.1%). This method was successfully applied to determine Aß peptides in CSF samples obtained from AD patients (n = 8) and controls (healthy volunteers, n = 10). Results showed that Aß42 levels in the CSF samples obtained from AD patients were significantly lower compared to healthy controls (p < 0.05). On the basis of the ROC analysis results, the Aß42/Aß40 ratio (AUC = 0.950, p < 0.01; 95%) performed significantly better than Aß42 alone (AUC = 0.913, p < 0.01; 95%) in discriminating between AD patients and healthy controls and presented better diagnostic ability for AD. The novelties of this study are not only related to evaluating Aß peptides as AD biomarkers, but also to demonstrating direct online coupling of fiber-in-tube SPME with MS/MS as a quantitative high-throughput method for bioanalysis.

The Effect of Cannabidiol for Restless Legs Syndrome/Willis-Ekbom Disease in Parkinson's Disease Patients with REM Sleep Behavior Disorder: A Post Hoc Exploratory Analysis of Phase 2/3 Clinical Trial.

Background: Cannabidiol (CBD) is one of the main nonpsychoactive components of Cannabis sativa and may represent an alternative treatment for Restless Legs Syndrome/Willis-Ekbom Disease (RLS/WED) in patients with Parkinson's disease (PD) and REM (Rapid Eye Movement) sleep behavior disorder (RBD). Objective: Our purpose was a post hoc exploratory analysis to evaluate the CBD's efficacy to improve the severity of RLS/WED symptoms in patients with PD and RBD. Methods: A post hoc exploratory analysis of a phase II/III, a parallel, double-blind, placebo-controlled clinical trial was conducted in 18 patients with RLS/WED and PD plus RBD associated. Six patients were randomized to the CBD group in doses of 75-300 mg, and twelve received placebo capsules. They were followed up for 14 weeks. The primary outcome was the severity of RLS/WED by Restless Legs Syndrome Rating Scale of the International Restless Legs Syndrome Study Group (IRLSSG). Results: CBD showed no difference in relationship to placebo for primary and secondary outcomes. Conclusion: CBD showed no reduction in the severity of RLS/WED manifestation in patients with PD and RBD.

Structural and functional differences in the brains of patients with MCI with and without depressive symptoms and their relations with Alzheimer's disease: an MRI study.

Background: The mild cognitive impairment (MCI) stage among elderly individuals is very complex, and the level of diagnostic accuracy is far from ideal. Some studies have tried to improve the 'MCI due to Alzheimer's disease (AD)' classification by further stratifying these patients into subgroups. Depression-related symptoms may play an important role in helping to better define the MCI stage in elderly individuals. Objective: In this work, we explored functional and structural differences in the brains of patients with nondepressed MCI (nDMCI) and patients with MCI with depressive symptoms (DMCI), and we examined how these groups relate to AD atrophy patterns and cognitive functioning. Methods: Sixty-five participants underwent MRI exams and were divided into four groups: cognitively normal, nDMCI, DMCI, and AD. We compared the regional brain volumes, cortical thickness, and white matter microstructure measures using diffusion tensor imaging among groups. Additionally, we evaluated changes in functional connectivity using fMRI data. Results: In comparison to the nDMCI group, the DMCI patients had more pronounced atrophy in the hippocampus and amygdala. Additionally, DMCI patients had asymmetric damage in the limbic-frontal white matter connection. Furthermore, two medial posterior regions, the isthmus of cingulate gyrus and especially the lingual gyrus, had high importance in the structural and functional differentiation between the two groups. Conclusion: It is possible to differentiate nDMCI from DMCI patients using MRI techniques, which may contribute to a better characterization of subtypes of the MCI stage.

Floor and ceiling effects on the Montreal Cognitive Assessment in patients with Parkinson's disease in Brazil / Efeitos solo e teto na Avaliação Cognitiva de Montreal em pacientes com doença de Parkinson no Brasil

ABSTRACT Parkinson's disease (PD) is a common neurodegenerative disease associated with cognitive impairment. The Montreal Cognitive Assessment (MoCA) has been used as a recommended global cognition scale for patients with PD, but there are some concerns about its application, partially due to the floor and ceiling effects. Objective: To explore the floor and ceiling effects on the MoCA in patients with PD in Brazil. Methods: Cross-sectional study with data from patients with PD from five Brazilian Movement Disorders Clinics, excluding individuals with a possible diagnosis of dementia. We analyzed the total score of the MoCA, as well as its seven cognitive domains. The floor and ceiling effects were evaluated for the total MoCA score and domains. Multivariate analyses were performed to detect factors associated with floor and ceiling effects. Results: We evaluated data from 366 patients with PD and approximately 19% of individuals had less than five years of education. For the total MoCA score, there was no floor or ceiling effect. There was a floor effect in the abstraction and delayed memory recall domains in 20% of our sample. The ceiling effect was demonstrated in all domains (80.8% more common in naming and 89% orientation), except delayed recall. Education was the main factor associated with the floor and ceiling effects, independent of region, sex, age at evaluation, and disease duration. Conclusion: The floor and ceiling effects are present in specific domains of the MoCA in Brazil, with a strong impact on education. Further adaptations of the MoCA structure for underrepresented populations may reduce these negative effects.

RESUMO A doença de Parkinson (DP) é uma doença neurodegenerativa comum associada ao declínio cognitivo. A Avaliação Cognitiva de Montreal (Montreal Cognitive Assessment — MoCA) tem sido usada como uma escala de cognição global recomendada para pacientes com DP, mas existem algumas preocupações sobre sua aplicação, em parte pelos efeitos solo e teto. Objetivo: Explorar os efeitos solo e teto na MoCA em pacientes com DP no Brasil. Métodos: Estudo transversal com dados de pacientes com DP oriundos de cinco Clínicas de Distúrbios de Movimento no Brasil, excluindo-se pessoas com possível diagnóstico de demência. Nós analisamos a pontuação total da MoCA, assim como a de seus sete domínios cognitivos. Os efeitos solo e teto foram avaliados para a pontuação total da MoCA e seus domínios. Foram feitas análises multivariadas para a detecção de fatores associados os efeitos solo e teto. Resultados: Nós avaliamos dados de 366 pacientes com DP, e aproximadamente 19% das pessoas tinham menos que cinco anos de escolaridade. Para a pontuação total do MoCA, não houve efeito solo ou teto. Houve efeito solo nos domínios abstração e memória de evocação tardia em 20% de nossa amostra. O efeito teto foi demonstrado em todos os domínios (80,8% mais comum em nomeação e 89% orientação), com exceção de memória de evocação tardia. A educação foi o principal fator associado aos efeitos solo e teto, independentemente de região, sexo, idade na avaliação e duração da doença. Conclusão: Os efeitos solo e teto estão presentes em domínios específicos da MoCA no Brasil, com forte impacto da educação. Adaptações adicionais à estrutura da MoCA para populações vulneráveis podem reduzir esses efeitos negativos.

Diagnosis and management of Parkinson's disease dementia and dementia with Lewy bodies: recommendations of the Scientific Department of Cognitive Neurology and Aging of the Brazilian Academy of Neurology.

Parkinson's disease dementia (PDD) and dementia with Lewy bodies (DLB) represent the second most common type of degenerative dementia in patients aged 65 years and older, leading to progressive cognitive dysfunction and impaired quality of life. This study aims to provide a consensus based on a systematic Brazilian literature review and a comprehensive international review concerning PDD and DLB. Moreover, we sought to report on and give recommendations about the best diagnostic approaches focusing on primary and secondary care. Based on the available data, we recommend clinicians to apply at least one brief global cognitive instrument to assess PDD, such as the Mini-Mental State Examination and preferably the Montreal Cognitive Assessment and the Addenbrooke's Cognitive Examination-Revised. Validated instruments to accurately assess functional abilities in Brazilian PD patients are still incipient. Further studies should focus on biomarkers with Brazilian cohorts.

A demência da doença de Parkinson (DDP) e a demência com corpos de Lewy (DCL) representam a segunda causa mais comum de demência neurodegenerativa em pessoas com mais de 65 anos, ocasionando progressivo declínio cognitivo e comprometimento da qualidade de vida. O presente estudo tem como objetivo prover um consenso de especialistas sobre a DDP e DCL, baseado em revisão sistemática da literatura brasileira e revisão não-sistemática de literatura internacional. Ademais, tal estudo visa promover informação e conceder recomendações sobre abordagem diagnóstica, com foco nos níveis de atenção primária e secundária em saúde. Com base nos dados disponíveis, recomendamos que os profissionais realizem pelo menos um breve instrumento cognitivo global, como o Mini-Exame do Estado Mental, contudo de preferência optem pela Avaliação Cognitiva de Montreal e o Exame Cognitivo de Addenbrooke-Revisado. Observa-se uma carência de instrumentos validados para a avaliação precisa das habilidades funcionais em pacientes brasileiros com DDP e DCL. Além disso, mais estudos focando em biomarcadores com coortes brasileiras também são necessários.