Frequency of Hereditary and GBA1-Related Parkinsonism in Latin America: A Systematic Review and Meta-Analysis.

BACKGROUND: Identifying hereditary parkinsonism is valuable for diagnosis, genetic counseling, patient prioritization in trials, and studying the disease for personalized therapies. However, most studies were conducted in Europeans, and limited data exist on admixed populations like those from Latin America. OBJECTIVES: This study aims to assess the frequency and distribution of genetic parkinsonism in Latin America. METHODS: We conducted a systematic review and meta-analysis of the frequency of parkinsonian syndromes associated with genetic pathogenic variants in Latin America. We defined hereditary parkinsonism as those caused by the genes outlined by the MDS Nomenclature of Genetic Movement Disorders and heterozygous carriers of GBA1 pathogenic variants. A systematic search was conducted in PubMed, Web of Science, Embase, and LILACS in August 2022. Researchers reviewed titles and abstracts, and disagreements were resolved by a third researcher. After this screening, five researchers reanalyzed the selection criteria and extracted information based on the full paper. The frequency for each parkinsonism-related gene was determined by the presence of pathogenic/likely pathogenic variants among screened patients. Cochran's Q and I2 tests were used to quantify heterogeneity. Meta-regression, publication bias tests, and sensitivity analysis regarding study quality were also used for LRRK2-, PRKN-, and GBA1-related papers. RESULTS: We included 73 studies involving 3014 screened studies from 16 countries. Among 7668 Latin American patients, pathogenic variants were found in 19 different genes. The frequency of the pathogenic variants in LRRK2 was 1.38% (95% confidence interval [CI]: 0.52-2.57), PRKN was 1.16% (95% CI: 0.08-3.05), and GBA1 was 4.17% (95% CI: 2.57-6.08). For all meta-analysis, heterogeneity was high and publication bias tests were negative, except for PRKN, which was contradictory. Information on the number of pathogenic variants in the other genes is further presented in the text. CONCLUSIONS: This study provides insights into hereditary and GBA1-related parkinsonism in Latin America. Lower GBA1 frequencies compared to European/North American cohorts may result from limited access to gene sequencing. Further research is vital for regional prevalence understanding, enabling personalized care and therapies. © 2023 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

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.

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.

Feasibility and effectiveness of a remote individual rehabilitation program for people with Parkinson's disease living in the Brazilian Amazon: a randomized clinical trial.

Parkinson's disease (PD) is a chronic and progressive neurodegenerative disorder, and the current treatment involves pharmacological intervention and physiotherapy. Telerehabilitation, which involves remote support and guidance for patients undergoing rehabilitation, can potentially improve access to physiotherapy services for people with Parkinson's disease, especially those who face geographic barriers to healthcare. The primary aim of this study was to assess the feasibility and efficacy of a telerehabilitation program for people with Parkinson's disease living in an underrepresented community of the Brazilian Amazon. We conducted a parallel-group, single-center, single-blind, phase 2 randomized controlled clinical trial involving 19 participants diagnosed with Parkinson's disease from Belém, Brazil. Participants were assigned to a 4-week individual telerehabilitation program or a booklet-based exercise program (control group). Assessments were conducted before the intervention, immediately after the intervention, and 4 weeks after the end of the intervention. We showed that our telerehabilitation program had high adherence among patients, with minimal adverse effects. Both telerehabilitation and booklet orientation reduced the time to complete the Timed Up and Go test. In conclusion, our telerehabilitation program was feasible and effective for people with Parkinson's disease in an Amazonian setting. This trial was registered at the Registro Brasileiro de Ensaios Clínicos (ReBEC) under the identifier: RBR-6sz837s.

Investigation of PRKN Mutations in Levodopa-Induced Dyskinesia in Parkinson's Disease Treatment.

Mitophagy is an important process that participates in mitochondrial quality control. Dysfunctions in this process can be caused by mutations in genes like PRKN and are associated with the development and progression of Parkinson's Disease (PD). The most used drug in the treatment of PD is levodopa (LD), but it can cause adverse effects, such as dyskinesia. Currently, few studies are searching for biomarkers for an effective use of lLD for this disease, especially regarding mitophagy genetics. Thus, this work investigates the association of 14 variants of the PRKN gene with LD in the treatment of PD. We recruited 70 patients with PD undergoing treatment with LD (39 without dyskinesia and 31 with dyskinesia). Genotyping was based on Sanger sequencing. Our results reinforce that age at onset of symptoms, duration of PD, and treatment and dosage of LD can influence the occurrence of dyskinesia but not the investigated PRKN variants. The perspective presented here of variants of mitophagy-related genes in the context of treatment with LD is still underexplored, although an association has been indicated in previous studies. We suggest that other variants in PRKN or in other mitophagy genes may participate in the development of levodopa-induced dyskinesia in PD treatment.

The role of sex and handedness in the performance of the smartphone-based Finger-Tapping Test.

The Finger Tapping Test (FTT) is a classical neuropsychological test that assesses motor functioning, and recently it has been employed using smartphones. For classical protocols, it has been observed that sex and handedness influence the performance during the test. By assessing the influence of sex and handedness on the test, it is possible to adjust the performance measurements to ensure the validity of test results and avoid sex- and handedness-related bias. The present study aimed to evaluate the influence of sex and handedness on smartphone-based FTT performance. We developed an Android application for the FTT and recruited 40 males and 40 females to carry out three spatial designs on it (protocols I, II, and III). Participants' performance was measured using the global, temporal, and spatial parameters of the FTT. We observed that for the performance in protocol I, handedness had a significant influence on global and temporal variables, while the interaction between handedness and sex had a greater influence on spatial variables. For protocols II and III, we observed that handedness had a significant influence on global, temporal, and spatial variables compared to the other factors. We concluded that the smartphone-based test is partly influenced by handedness and sex, and in clinical implications, these factors should be considered during the evaluation of the smartphone-based FTT.

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.

There is no shortage, but inequality: demographic evolution of neurologists in Brazil (2010-2020).

BACKGROUND: Neurology is a medical specialty that deals with prevalent diseases such as stroke, headache, epilepsy, and neurodegenerative diseases. Many countries, such as Brazil, struggle to provide neurological care for their populations, but the inadequacy and unequal distribution of the neurologist workforce are real challenges. OBJECTIVE: To analyze the demographic evolution of neurologists and the first-year Neurology residency positions in Brazil during the last decade (2010-2020) and the distribution imbalance between regions. METHODS: The demographic and geographic distribution of neurologists was calculated based on data extracted from the Brazilian Federal Medical Council reports, and the number of Neurology residency positions was based on the Brazilian National Commission of Medical Residency reports. Indicators of wealth were associated with demographic data. RESULTS: The number of neurologists per 100,000 population has increased since 2011, with a similar increase in the geographic distribution of neurologists. However, there was a marked inequality of distribution of neurologists through regions, with a gap between the Northern (lowest) and Southeastern (highest) regions. Furthermore, the imbalance of distribution of neurologists strongly correlated with social inequality. The number of Neurology residency positions increased, but with an imbalance between North and Southeast regions. CONCLUSIONS: Brazil has advanced in providing neurologists. However, instead of a shortage, inequality between regions is the greatest challenge regarding the neurological workforce. The training of new neurologists is unequal between regions and occurs at a slower rate than needed. Neurologists, public health authorities, and patients should discuss solutions for these issues.

ANTECEDENTES: A Neurologia é uma especialidade médica que lida com doenças prevalentes, como acidente vascular cerebral, cefaleia, epilepsia e doenças neurodegenerativas. Muitos países, como o Brasil, se esforçam para oferecer assistência neurológica à população, mas a distribuição insuficiente e desigual da força de trabalho de neurologistas são desafios. OBJETIVO: Analisar a evolução demográfica dos médicos neurologistas e das vagas de Programas de Residência Médica em Neurologia no Brasil durante a última década (2010-2020) e o desequilíbrio de distribuição entre as regiões. MéTODOS: A distribuição demográfica e geográfica de neurologistas foi calculada com base nos dados extraídos de relatórios do Conselho Federal do Medicina do Brasil, e o número de vagas em Programas de Residência Médica em Neurologia foi extraído de dados da Comissão Nacional de Residência Médica. Os indicadores de riqueza foram associados aos dados demográficos. RESULTADOS: O número de neurologistas por 100.000 habitantes aumentou desde 2011, com um aumento similar na distribuição geográfica de neurologistas. Entretanto, houve uma nítida desigualdade na distribuição de neurologistas entre as regiões, com um hiato entre as regiões Norte e a Sudeste. Além disso, a desigualdade da distribuição de neurologistas se correlacionou fortemente com a desigualdade social. O número de vagas em Programas de Residência Médica aumentou, porém com desigualdade entre as regiões Norte e Sudeste. CONCLUSõES: O Brasil tem avançado na geração de neurologistas. Porém, ao invés de uma escassez, a desigualdade entre regiões é o maior desafio em relação à força de trabalho neurológica. O treino de novos neurologistas é desigual entre regiões e ocorre em um ritmo mais lento do que o necessário. Neurologistas, autoridades em saúde pública e pacientes devem discutir soluções para estes problemas.

Physical activity based on dance movements as complementary therapy for Parkinson's disease: Effects on movement, executive functions, depressive symptoms, and quality of life.

BACKGROUND: Parkinson's disease (PD) is a progressive, neurodegenerative disease with motor symptoms that are well understood, but non-motor symptoms may be present and appear at different temporal stages of the disease. Physical activity based on dance movements is emerging as a complementary therapeutic approach to a range of PD symptoms as a multidimensional activity that requires rhythmic synchronization and more neuromuscular functions. OBJECTIVE: To evaluate the effects of physical activity based on dance movements on the movement, executive functions, depressive symptoms, quality of life, and severity of PD in individuals diagnosed with PD. METHODS: 13 individuals with PD (Hoehn & Yahr I-III, MDS-UPDRS 67.62 ± 20.83), underwent physical activity based on dance movements (2x week for 6 months). Participants were assessed at baseline and after 6 months on movement (POMA, TUG and MDS-UPDRS Part III), executive function (FAB), depressive symptoms (MADRS), quality of life (PDQ-39), and severity of PD (MDS-UPDRS TOTAL). Student's t-test was used to compare pre and post-intervention results. RESULTS: We observed a significant improvement in the movement (balance and gait) by the POMA test, p = 0.0207, executive function by the FAB test, p = 0.0074, abstract reasoning and inhibitory control by the FAB, Conceptualization test, p = 0.0062, and Inhibitory Control, p = 0.0064, depressive symptoms assessed by the MADRS test significantly reduced, p = 0.0214, and the quality of life by the PDQ-39 had a significant increase after the intervention, p = 0.0006, showed significant improvements between the pre-and post-intervention periods of physical activity based on dance movements. CONCLUSION: Physical activity based on dance movements contributed to significant improvements in movement (balance and gait), executive functions, especially in cognitive flexibility and inhibitory control, and the quality of life too. Sensorimotor integration, most cognitive processing and social skills may have contributed to the results. TRIAL REGISTRATION: The study was registered in the Brazilian registry of clinical trials: RBR-3bhbrb5.

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.

There is no shortage, but inequality: demographic evolution of neurologists in Brazil (2010-2020) / Não há escassez, mas sim desigualdade: evolução demográfica de neurologistas no Brasil (2010-2020)

Abstract Background Neurology is a medical specialty that deals with prevalent diseases such as stroke, headache, epilepsy, and neurodegenerative diseases. Many countries, such as Brazil, struggle to provide neurological care for their populations, but the inadequacy and unequal distribution of the neurologist workforce are real challenges. Objective To analyze the demographic evolution of neurologists and the first-year Neurology residency positions in Brazil during the last decade (2010-2020) and the distribution imbalance between regions. Methods The demographic and geographic distribution of neurologists was calculated based on data extracted from the Brazilian Federal Medical Council reports, and the number of Neurology residency positions was based on the Brazilian National Commission of Medical Residency reports. Indicators of wealth were associated with demographic data. Results The number of neurologists per 100,000 population has increased since 2011, with a similar increase in the geographic distribution of neurologists. However, there was a marked inequality of distribution of neurologists through regions, with a gap between the Northern (lowest) and Southeastern (highest) regions. Furthermore, the imbalance of distribution of neurologists strongly correlated with social inequality. The number of Neurology residency positions increased, but with an imbalance between North and Southeast regions. Conclusions Brazil has advanced in providing neurologists. However, instead of a shortage, inequality between regions is the greatest challenge regarding the neurological workforce. The training of new neurologists is unequal between regions and occurs at a slower rate than needed. Neurologists, public health authorities, and patients should discuss solutions for these issues.

Resumo Antecedentes A Neurologia é uma especialidade médica que lida com doenças prevalentes, como acidente vascular cerebral, cefaleia, epilepsia e doenças neurodegenerativas. Muitos países, como o Brasil, se esforçam para oferecer assistência neurológica à população, mas a distribuição insuficiente e desigual da força de trabalho de neurologistas são desafios. Objetivo Analisar a evolução demográfica dos médicos neurologistas e das vagas de Programas de Residência Médica em Neurologia no Brasil durante a última década (2010-2020) e o desequilíbrio de distribuição entre as regiões. Métodos A distribuição demográfica e geográfica de neurologistas foi calculada com base nos dados extraídos de relatórios do Conselho Federal do Medicina do Brasil, e o número de vagas em Programas de Residência Médica em Neurologia foi extraído de dados da Comissão Nacional de Residência Médica. Os indicadores de riqueza foram associados aos dados demográficos. Resultados O número de neurologistas por 100.000 habitantes aumentou desde 2011, com um aumento similar na distribuição geográfica de neurologistas. Entretanto, houve uma nítida desigualdade na distribuição de neurologistas entre as regiões, com um hiato entre as regiões Norte e a Sudeste. Além disso, a desigualdade da distribuição de neurologistas se correlacionou fortemente com a desigualdade social. O número de vagas em Programas de Residência Médica aumentou, porém com desigualdade entre as regiões Norte e Sudeste. Conclusões O Brasil tem avançado na geração de neurologistas. Porém, ao invés de uma escassez, a desigualdade entre regiões é o maior desafio em relação à força de trabalho neurológica. O treino de novos neurologistas é desigual entre regiões e ocorre em um ritmo mais lento do que o necessário. Neurologistas, autoridades em saúde pública e pacientes devem discutir soluções para estes problemas.

The hand tremor spectrum is modified by the inertial sensor mass during lightweight wearable and smartphone-based assessment in healthy young subjects.

Tremors are common disorders characterized by an involuntary and relatively rhythmic oscillation that can occur in any part of the body and may be physiological or associated with some pathological condition. It is known that the mass loading can change the power spectral distribution of the tremor. Nowadays, many instruments have been used in the evaluation of tremors with bult-in inertial sensors, such as smartphones and wearables, which can significantly differ in the device mass. The aim of this study was to compare the quantification of hand tremor using Fourier spectral techniques obtained from readings of accelerometers built-in a lightweight handheld device and a commercial smartphone in healthy young subjects. We recruited 28 healthy right-handed subjects with ages ranging from 18 to 40 years. We tested hand tremors at rest and postural conditions using lightweight wearable device (5.7 g) and smartphone (169 g). Comparing both devices at resting tremor, we found with smartphone the power distribution of peak ranging 5 and 12 Hz in both hands. With wearable, the result was similar but less evident. When comparing both devices in postural tremor, there were significant differences in both frequency ranges in peak frequency and peak amplitude in both hands. Our main findings show that in resting condition the hand tremor spectrum had a higher peak amplitude in the 5-12 Hz range when the tremor was recorded with smartphones, and in postural condition there was a significantly (p < 0.05) higher peak power spectrum and peak frequency in the dominant hand tremors recorded with smartphones compared to those obtained with lightweight wearable device. Devices having different masses can alter the features of the hand tremor spectrum and their mutual comparisons can be prejudiced.

Lack of full sequencing GBA1 studies for patients with Parkinson's disease in Latin America.

Full sequencing of the GBA1 gene in patients with Parkinson's disease provides a wide screening of pathogenic variants, but less developed regions of the world, like Latin America, may have difficulties in performing full sequencing. We performed a systematic review with meta-analysis to explore the prevalence and the odds ratio of specific GBA1 variants in Parkinson's disease in Latin America. We noted a lack of full sequencing GBA1 studies in Latin America.

Wearable Devices and Smartphone Inertial Sensors for Static Balance Assessment: A Concurrent Validity Study in Young Adult Population.

Falls represent a public health issue around the world and prevention is an important part of the politics of many countries. The standard method of evaluating balance is posturography using a force platform, which has high financial costs. Other instruments, such as portable devices and smartphones, have been evaluated as low-cost alternatives to the screening of balance control. Although smartphones and wearables have different sizes, shapes, and weights, they have been systematically validated for static balance control tasks. Different studies have applied different experimental configurations to validate the inertial measurements obtained by these devices. We aim to evaluate the concurrent validity of a smartphone and a portable device for the evaluation of static balance control in the same group of participants. Twenty-six healthy and young subjects comprised the sample. The validity for static balance control evaluation of built-in accelerometers inside portable smartphone and wearable devices was tested considering force platform recordings as a gold standard for comparisons. A linear correlation (r) between the quantitative variables obtained from the inertial sensors and the force platform was used as an indicator of the concurrent validity. Reliability of the measures was calculated using Intraclass correlation in a subsample (n = 14). Smartphones had 11 out of 12 variables with significant moderate to very high correlation (r > 0.5, p < 0.05) with force platform variables in open eyes, closed eyes, and unipedal conditions, while wearable devices had 8 out of 12 variables with moderate to very high correlation (r > 0.5, p < 0.05) with force platform variables under the same task conditions. Significant reliabilities were found in closed eye conditions for smartphones and wearables. The smartphone and wearable devices had concurrent validity for the static balance evaluation and the smartphone had better validity results than the wearables for the static balance evaluation.

Underrepresented Populations in Parkinson's Genetics Research: Current Landscape and Future Directions.

BACKGROUND: Human genetics research lacks diversity; over 80% of genome-wide association studies have been conducted on individuals of European ancestry. In addition to limiting insights regarding disease mechanisms, disproportionate representation can create disparities preventing equitable implementation of personalized medicine. OBJECTIVE: This systematic review provides an overview of research involving Parkinson's disease (PD) genetics in underrepresented populations (URP) and sets a baseline to measure the future impact of current efforts in those populations. METHODS: We searched PubMed and EMBASE until October 2021 using search strings for "PD," "genetics," the main "URP," and and the countries in Latin America, Caribbean, Africa, Asia, and Oceania (excluding Australia and New Zealand). Inclusion criteria were original studies, written in English, reporting genetic results on PD from non-European populations. Two levels of independent reviewers identified and extracted information. RESULTS: We observed imbalances in PD genetic studies among URPs. Asian participants from Greater China were described in the majority of the articles published (57%), but other populations were less well studied; for example, Blacks were represented in just 4.0% of the publications. Also, although idiopathic PD was more studied than monogenic forms of the disease, most studies analyzed a limited number of genetic variants. We identified just nine studies using a genome-wide approach published up to 2021, including URPs. CONCLUSION: This review provides insight into the significant lack of population diversity in PD research highlighting the immediate need for better representation. The Global Parkinson's Genetics Program (GP2) and similar initiatives aim to impact research in URPs, and the early metrics presented here can be used to measure progress in the field of PD genetics in the future. © 2022 International Parkinson and Movement Disorder Society.

Case report: Cerebellar sparing in juvenile Huntington's disease.

Juvenile Huntington's disease is an early-onset variant of Huntington's disease, generally associated with large CAG repeats and distinct clinical symptoms. The role of the cerebellum in Huntington's disease has been reevaluated, based on the presence of ataxia and findings on the impact of the disease on cerebellar volume. Recent studies showed a hyperconnectivity between the cerebellum and the basal ganglia in premanifest children with expanded CAG repeats, as well as an enlargement of the cerebellum in adolescence-onset Huntington's disease. We report a 21-year-old Brazilian female with Huntington's disease (age at disease onset 16 years) with Parkinsonism and no ataxic features. There was no reduction of cerebellar volume over 3 years of follow-up, despite the brain atrophy in other regions and clinical worsening. Furthermore, the cerebellar volume of the patient was similar to age- and sex-matched controls. These findings support the existence of compensatory mechanisms involving the cerebellum in individuals with a moderate-to-high number of CAG repeats (50-100 copies) in the early stages of life.

Regulatory miRNA-mRNA Networks in Parkinson's Disease.

Parkinson's disease (PD) is the second-most common neurodegenerative disease, and its pathophysiology is associated with alpha-synuclein accumulation, oxidative stress, mitochondrial dysfunction, and neuroinflammation. MicroRNAs are small non-coding RNAs that regulate gene expression, and many previous studies have described their dysregulation in plasma, CSF, and in the brain of patients with PD. In this study, we aimed to provide a regulatory network analysis on differentially expressed miRNAs in the brain of patients with PD. Based on our systematic review with a focus on the substantia nigra and the putamen, we found 99 differentially expressed miRNAs in brain samples from patients with PD, which regulate 135 target genes. Five genes associated with neuronal survival (BCL2, CCND1, FOXO3, MYC, and SIRT1) were modulated by dysregulated miRNAs found in the substantia nigra and the putamen of patients with PD. The functional enrichment analysis found FoxO and PI3K-AKT signaling as pathways related to PD. In conclusion, our comprehensive analysis of brain-related miRNA-mRNA regulatory networks in PD showed that mechanisms involving neuronal survival signaling, such as cell cycle control and regulation of autophagy/apoptosis, may be crucial for the neurodegeneration of PD, being a promising way for novel disease-modifying therapies.