Diffusion tensor metrics, motor and non-motor symptoms in de novo Parkinson's disease.

INTRODUCTION: Parkinson's disease (PD) is a neurodegenerative disorder characterized by dopaminergic neurons' degeneration of the substantia nigra, presenting with motor and non-motor symptoms. We hypothesized that altered diffusion metrics are associated with clinical symptoms in de novo PD patients. METHODS: Fractional Anisotropy (FA) and Mean (MD), Axial (AD), and Radial Diffusivity (RD) were assessed in 55 de novo PD patients (58.62 ± 9.85 years, 37 men) and 55 age-matched healthy controls (59.92 ± 11.25 years, 34 men). Diffusion-weighted images and clinical variables were collected from the Parkinson's Progression Markers Initiative study. Tract-based spatial statistics were used to identify white matter (WM) changes, and fiber tracts were localized using the JHU-WM tractography atlas. Motor and non-motor symptoms were evaluated in patients. RESULTS: We observed higher FA values and lower RD values in patients than controls in various fiber tracts (p-TFCE < 0.05). No significant MD or AD difference was observed between groups. Diffusion metrics of several regions significantly correlated with non-motor (state and trait anxiety and daytime sleepiness) and axial motor symptoms in the de novo PD group. No correlations were observed between diffusion metrics and other clinical symptoms evaluated. CONCLUSION: Our findings suggest microstructural changes in de novo PD fiber tracts; however, limited associations with clinical symptoms reveal the complexity of PD pathology. They may contribute to understanding the neurobiological changes underlying PD and have implications for developing targeted interventions. However, further longitudinal research with larger cohorts and consideration of confounding factors are necessary to elucidate the underlying mechanisms of these diffusion alterations in de novo PD.

Parkinson's Disease Gene Screening in Familial Cases from Central and South America.

BACKGROUND: Parkinson's disease (PD) is the second most common neurodegenerative disease following Alzheimer's disease. Nearly 30 causative genes have been identified for PD and related disorders. However, most of these genes were identified in European-derived families, and little is known about their role in Latin American populations. OBJECTIVES: Our goal was to assess the spectrum and frequency of pathogenic variants in known PD genes in familial PD patients from Latin America. METHODS: We selected 335 PD patients with a family history of PD from the Latin American Research Consortium on the Genetics of PD. We capture-sequenced the coding regions of 26 genes related to neurodegenerative parkinsonism. Of the 335 PD patients, 324 had sufficient sequencing coverage to be analyzed. RESULTS: We identified pathogenic variants in 41 individuals (12.7%) in FBXO7, GCH1, LRRK2, PARK7, PINK1, PLA2G6, PRKN, SNCA, and TARDBP, GBA1 risk variants in 25 individuals (7.7%), and variants of uncertain significance in another 24 individuals (7.4%) in ATP13A2, ATP1A3, DNAJC13, DNAJC6, GBA1, LRKK2, PINK1, VPS13C, and VPS35. Of the 70 unique variants identified, 19 were more frequent in Latin Americans than in any other population. CONCLUSIONS: This is the first screening of known PD genes in a large cohort of patients with familial PD from Latin America. There were substantial differences in the spectrum of variants observed in comparison to previous findings from PD families of European origin. Our data provide further evidence that differences exist between the genetic architecture of PD in Latinos and European-derived populations. © 2024 The Author(s). Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Stereotatic radiosurgery for the treatment of motor symptoms in Parkinson's disease: A systematic review.

BACKGROUND: Stereotaxic Radiosurgery (SRS) is a non-invasive lesioning technique for movement disorders when patients cannot undergo DBS due to medical comorbidities. OBJECTIVE: To describe and summarize the literature on SRS's application and physical parameters for Parkinson's disease (PD) motor symptoms. METHODS: The MEDLINE/PUBMED and EMBASE databases were searched in July 2022 following the PRISMA guideline. Two independent reviewers screened data from 425 articles. The level of evidence followed the Oxford Centre for Evidence-Based Medicine. Pertinent details for each study regarding participants, physical parameters, and results were extracted. RESULTS: Twelve studies reported that 454 PD patients underwent Gamma KnifeⓇ (GK). The mean improvement time of the treated symptoms was three months after GK. Tremor is the most common symptom investigated, with success rates ranging from 47.5% to 93.9%. Few studies were conducted for caudatotomy (GKC) and pallidotomy (GKP), which presented an improvement for dyskinesia and bradykinesia. Physical parameters were similar with doses ranging from 110 to 200 Gy, use of a 4-mm collimator with an advanced imaging locator system, and coordinates were obtained from available stereotactic atlases. CONCLUSIONS: GK thalamotomy is a good alternative for treating tremor; however, its effects are delayed, and there are cases in which it can regress after years. The outcomes of GKC and GKP seem to be promising. The existing studies are more limited, and effects need to be better investigated.

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.

Handicap as a Measure of Perceived-Health Status in Parkinson's Disease.

Background: Handicap is a patient-centered measure of health status that encompasses the impact of social and physical environment on daily living, having been assessed in advanced and late-stage Parkinson's Disease (PD). Objective: To characterize the handicap of a broader sample of patients. Methods: A cross-sectional study of 405 PD patients during the MDS-UPDRS Portuguese validation study, using the MDS-UPDRS, Unified Dyskinesias Rating Scale, Nonmotor symptoms questionnaire, PDQ-8 and EQ-5D-3L. Handicap was measured using the London Handicap Scale (LHS). Results: Mean age was 64.42 (±10.3) years, mean disease duration 11.30 (±6.5) years and median HY 2 (IQR, 2-3). Mean LHS was 0.652 (±0.204); "Mobility," "Occupation" and "Physical Independence" were the most affected domains. LHS was significantly worse in patients with longer disease duration, older age and increased disability. In contrast, PDQ-8 did not differentiate age groups. Handicap was significantly correlated with disease duration (r = -0.35), nonmotor experiences of daily living (EDL) (MDS-UPDRS-I) (r = -0.51), motor EDL (MDS-UPDRS-II) (r = -0.69), motor disability (MDS-UPDRS-III) (r = -0.49), axial signs of MDS-UPDRS-III (r = -0.55), HY (r = -0.44), presence of nonmotor symptoms (r = -0.51) and PDQ-8 index (r = -0.64) (all P < 0.05). Motor EDL, MDS-UPDRS-III and PDQ-8 independently predicted Handicap (adjusted R 2 = 0.582; P = 0.007). Conclusions: The LHS was easily completed by patients and caregivers. Patients were mild-moderately handicapped, which was strongly determined by motor disability and its impact on EDL, and poor QoL. Despite correlated, handicap and QoL seem to differ in what they measure, and handicap may have an added value to QoL. Handicap seems to be a good measure of perceived-health status in a broad sample of PD.

Brazilian headache registry: methods and preliminary data of the pilot study.

BACKGROUND: Evaluation and treatment of primary and secondary headaches is a global public health challenge. Recognizing the epidemiological impact of headaches, a group of researchers linked to the Brazilian Headache Society proposed the Brazilian Headache Registry and drew up its initial protocol. OBJECTIVE: Here we describe the methods and preliminary data obtained from the pilot study. METHODS: This was a multicenter longitudinal observational study conducted between September 2020 and August 2021. Prospective data were collected in three specialist centers for headache care in states in southern and southeastern Brazil. Patients aged 18 years or older who sought care for headache in tertiary centers and who agreed to participate in the study, were considered eligible. RESULTS: Sixty-six patients were included in the pilot study: 43 (65%) from Rio Grande do Sul state and 23 (35%) from Minas Gerais state. Overall, 90% were female, and the subjects' mean age was 38.2 ± 11.2 years. Primary headaches accounted for 85.3% of the diagnoses made. Among secondary headaches, medication overuse headache was the most frequent type (7.1%). CONCLUSIONS: The pilot study showed the feasibility of the research protocol developed for tertiary centers. The Brazilian Headache Registry will form a source of longitudinal data with the aim of contributing to better characterization of the various phenotypes of patients with primary and secondary headaches, and to detailing the use of health resources and identifying predictors of better clinical outcomes.

ANTECEDENTES: A avaliação e o tratamento das cefaleias primárias e secundárias são um desafio global de saúde pública. Reconhecendo o impacto epidemiológico das cefaleias, um grupo de pesquisadores vinculados à Sociedade Brasileira de Cefaleia propôs a criação de um Registro Brasileiro de Cefaleia e elaborou seu protocolo inicial. OBJETIVO: Nesta publicação descrevemos os métodos e dados preliminares obtidos a partir do estudo piloto. MéTODOS: Trata-se de um estudo prospectivo observacional longitudinal multicêntrico, realizado entre setembro de 2020 e agosto de 2021. Foram coletados dados em três centros especializados no atendimento de cefaleia, em estados da região sul e sudeste do Brasil. Pacientes com idade igual ou superior a 18 anos que procuraram os centros terciários por queixa de cefaleia e concordaram em participar do estudo foram considerados elegíveis. RESULTADOS: Sessenta e seis pacientes foram incluídos no estudo piloto, 43 (65%) do Rio Grande do Sul e 23 (35%) de Minas Gerais. Da amostra total, 90% eram do sexo feminino e a idade média dos sujeitos foi de 38,2 ± 11,2 anos. As cefaleias primárias representaram 85,3% dos diagnósticos realizados. Entre as cefaleias secundárias, a cefaleia por uso excessivo de medicamentos foi a mais frequente (7,1%). CONCLUSõES: O estudo piloto evidenciou a viabilidade do protocolo de pesquisa desenvolvido para centros terciários. O Registro Brasileiro de Cefaleia constituirá uma fonte de dados longitudinais com o objetivo de contribuir para melhor caracterização dos diversos fenótipos de pacientes com cefaleias primárias e secundárias, detalhar o uso de recursos de saúde e identificar preditores de melhores desfechos clínicos.

Brazilian headache registry: methods and preliminary data of the pilot study / Registro brasileiro de cefaleia: métodos e dados preliminares do estudo piloto

Abstract Background Evaluation and treatment of primary and secondary headaches is a global public health challenge. Recognizing the epidemiological impact of headaches, a group of researchers linked to the Brazilian Headache Society proposed the Brazilian Headache Registry and drew up its initial protocol. Objective Here we describe the methods and preliminary data obtained from the pilot study. Methods This was a multicenter longitudinal observational study conducted between September 2020 and August 2021. Prospective data were collected in three specialist centers for headache care in states in southern and southeastern Brazil. Patients aged 18 years or older who sought care for headache in tertiary centers and who agreed to participate in the study, were considered eligible. Results Sixty-six patients were included in the pilot study: 43 (65%) from Rio Grande do Sul state and 23 (35%) from Minas Gerais state. Overall, 90% were female, and the subjects' mean age was 38.2 ± 11.2 years. Primary headaches accounted for 85.3% of the diagnoses made. Among secondary headaches, medication overuse headache was the most frequent type (7.1%). Conclusions The pilot study showed the feasibility of the research protocol developed for tertiary centers. The Brazilian Headache Registry will form a source of longitudinal data with the aim of contributing to better characterization of the various phenotypes of patients with primary and secondary headaches, and to detailing the use of health resources and identifying predictors of better clinical outcomes.

Resumo Antecedentes A avaliação e o tratamento das cefaleias primárias e secundárias são um desafio global de saúde pública. Reconhecendo o impacto epidemiológico das cefaleias, um grupo de pesquisadores vinculados à Sociedade Brasileira de Cefaleia propôs a criação de um Registro Brasileiro de Cefaleia e elaborou seu protocolo inicial. Objetivo Nesta publicação descrevemos os métodos e dados preliminares obtidos a partir do estudo piloto. Métodos Trata-se de um estudo prospectivo observacional longitudinal multicêntrico, realizado entre setembro de 2020 e agosto de 2021. Foram coletados dados em três centros especializados no atendimento de cefaleia, em estados da região sul e sudeste do Brasil. Pacientes com idade igual ou superior a 18 anos que procuraram os centros terciários por queixa de cefaleia e concordaram em participar do estudo foram considerados elegíveis. Resultados Sessenta e seis pacientes foram incluídos no estudo piloto, 43 (65%) do Rio Grande do Sul e 23 (35%) de Minas Gerais. Da amostra total, 90% eram do sexo feminino e a idade média dos sujeitos foi de 38,2 ± 11,2 anos. As cefaleias primárias representaram 85,3% dos diagnósticos realizados. Entre as cefaleias secundárias, a cefaleia por uso excessivo de medicamentos foi a mais frequente (7,1%). Conclusões O estudo piloto evidenciou a viabilidade do protocolo de pesquisa desenvolvido para centros terciários. O Registro Brasileiro de Cefaleia constituirá uma fonte de dados longitudinais com o objetivo de contribuir para melhor caracterização dos diversos fenótipos de pacientes com cefaleias primárias e secundárias, detalhar o uso de recursos de saúde e identificar preditores de melhores desfechos clínicos.

When should a university student be allowed academic accommodations for attention-deficit/hyperactivity disorder? A position statement for a unified procedure for use in Brazil

In higher education, reasonable accommodations are increasingly made for students with a wide range of disabilities. However, rigorous assessment is paramount to ensure these students are supported while preventing ineligible students from gaining unfair advantages. In this context, we sought to identify under which circumstances a university student should be allowed academic accommodation for attention-deficit/hyperactivity disorder (ADHD) and to outline an evidence-based policy for use in Brazil based on the global experience. We reviewed the literature to acquire information on what documents are commonly required by disability services before accommodations for ADHD are provided (including detection of malingering) and scrutinized the eligibility criteria of leading universities worldwide. Finally, renowned experts in the field and national stakeholders were consulted. Despite an exhaustive search, we found no international standard for the assessment of students with ADHD who request academic accommodation; even renowned institutions worldwide differ in their approaches to granting accommodations on the grounds of ADHD. Therefore, we propose a unified set of nationwide criteria for Brazilian universities, which could be generalized internationally. Higher education institutions in Brazil and beyond may benefit from adoption of such criteria.

X-Chromosome Association Study in Latin American Cohorts Identifies New Loci in Parkinson's Disease.

BACKGROUND: Sex differences in Parkinson's disease (PD) risk are well-known. However, the role of sex chromosomes in the development and progression of PD is still unclear. OBJECTIVE: The objective of this study was to perform the first X-chromosome-wide association study for PD risk in a Latin American cohort. METHODS: We used data from three admixed cohorts: (1) Latin American Research consortium on the Genetics of Parkinson's Disease (n = 1504) as discover cohort, and (2) Latino cohort from International Parkinson Disease Genomics Consortium (n = 155) and (3) Bambui Aging cohort (n = 1442) as replication cohorts. We also developed an X-chromosome framework specifically designed for admixed populations. RESULTS: We identified eight linkage disequilibrium regions associated with PD. We replicated one of these regions (top variant rs525496; discovery odds ratio [95% confidence interval]: 0.60 [0.478-0.77], P = 3.13 × 10-5 replication odds ratio: 0.60 [0.37-0.98], P = 0.04). rs5525496 is associated with multiple expression quantitative trait loci in brain and non-brain tissues, including RAB9B, H2BFM, TSMB15B, and GLRA4, but colocalization analysis suggests that rs5525496 may not mediate risk by expression of these genes. We also replicated a previous X-chromosome-wide association study finding (rs28602900), showing that this variant is associated with PD in non-European populations. CONCLUSIONS: Our results reinforce the importance of including X-chromosome and diverse populations in genetic studies. © 2023 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

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.

When should a university student be allowed academic accommodation For ADHD? A position statement for a unified procedure for use in Brazil.

OBJECTIVE: To identify under what circumstances a university student should be allowed academic accommodation for ADHD. To frame an evidence-based policy for use in Brazil based on a worldwide experience. METHODS: We reviewed the literature to acquire information on what documents are commonly required by disability services before accommodation for ADHD is made (including malingering detection). We scrutinized the eligibility criteria of the best universities worldwide. Renowned experts in the field and national stakeholders were consulted. RESULTS: We found no international standard for the assessment of students with ADHD who request academic accommodation. Even renowned institutions worldwide differ from one another in their approaches to academic accommodation on the grounds of ADHD. We propose a national unified set of criteria for Brazilian universities, which could generalize internationally. DISCUSSION: Rigorous assessment is paramount for aiding students with disabilities while preventing ineligible students gaining an unfair advantage. Higher education institutions nationwide and beyond may benefit from adopting a unified set of criteria for eligibility to ADHD accommodation programs.

Differences in spontaneous speech fluency between Parkinson's disease and spinocerebellar ataxia type 3.

Background: The basal ganglia and cerebellum both have a role in speech production although the effect of isolated involvement of these structures on speech fluency remains unclear. Objective: The study aimed to assess the differences in the articulatory pattern in patients with cerebellar vs. basal ganglia disorders. Methods: A total of 20 individuals with Parkinson's disease (PD), 20 with spinocerebellar ataxia type 3 (SCA3), and 40 controls (control group, CG) were included. Diadochokinesis (DDK) and monolog tasks were collected. Results: The only variable that distinguished SCA3 carriers from the CG was the number of syllables in the monolog, with SCA3 patients of a significantly lower number. For patients with PD, the number of syllables, phonation time, DDK, and monolog were significantly lower than for CG. Patients with PD were significantly worse compared to patients with SCA3 in the number of syllables and phonation time in DDK, and phonation time in monolog. Additionally, there was a significant correlation between the number of syllables in the monolog and the MDS-UPDRS III for participants with PD, and the Friedreich Ataxia Rating Scale for participants with SCA3 suggesting a relationship between speech and general motor functioning. Conclusion: The monolog task is better at discriminating individuals with cerebellar vs. Parkinson's diseases as well as differentiating healthy control and was related to the severity of the disease.

Low serum uric acid levels and levodopa-induced dyskinesia in Parkinson's disease.

BACKGROUND: Levodopa is the most used and effective medication for motor symptoms of Parkinson disease (PD), its long-term use is associated with the appearance of levodopa-induced dyskinesia (LID). Uric acid (UA) is believed to play an important neuroprotective role in PD. OBJECTIVE: To investigate if serum UA levels are related with the presence of LIDs in PD patients. Also, we investigated the associations among UA levels and clinical features of PD. METHODS: We enrolled 81 PD patients (dyskinesia = 48; no dyskinesia = 33) in the present study. A blood sample was collected to evaluate serum UA levels, clinical evaluation included the following instruments: Montreal Cognitive Assessment (MoCA), Beck Depression Inventory II (BDI-II), MDS-Unified Parkinson's Disease Rating Scale (MDS-UPDRS), Hoehn and Yahr (HY), and the sub-item 4.1 of MDS-UPDRS IV (score ≥ 1). Additional relevant clinical information was obtained by a clinical questionnaire. RESULTS: Serum UA levels were lower in the dyskinesia group when compared with the no dyskinesia group. The same result was found in the UA levels of both men and women. The multivariate analysis showed lower uric acid levels were significantly associated with having dyskinesia (odds ratio [OR] = 0.424; 95% confidence interval [CI]: 0.221-0.746; p = 0.005). Additional analysis verified that serum UA levels are inversely correlated with depressive symptoms, disease duration, MDS-UPDRS IV and time spent with dyskinesia. A positive correlation was found with age at onset of PD symptoms. CONCLUSIONS: The present study provides a possible role of serum UA levels in LID present in PD patients.

ANTECEDENTES: A levodopa é a medicação mais utilizada e eficaz para os sintomas motores da doença de Parkinson (DP); seu uso a longo prazo está associado ao aparecimento de discinesia induzida por levodopa (LID). Acredita-se que o ácido úrico desempenhe um importante papel neuroprotetor na DP. OBJETIVO: Investigar se os níveis séricos de AU estão relacionados com a presença de LID em pacientes com DP. Além disso, investigamos as associações entre os níveis de AU e as características clínicas da DP. MéTODOS: Foram incluídos 81 pacientes com DP (discinesia = 48; sem discinesia = 33) no presente estudo. Uma amostra de sangue foi coletada para avaliar os níveis séricos de AU, a avaliação clínica incluiu os seguintes instrumentos: Avaliação Cognitiva de Montreal (MoCA), Inventário de Depressão de Beck (BDI-II), MDS-Unified Parkinson's Disease Rating Scale (MDS-UPDRS), Hoehn and Yahr (HY) e o subitem 4.1 da MDS-UPDRS IV (escore ≥ 1). Informações clínicas relevantes adicionais foram obtidas por meio de um questionário clínico. RESULTADOS: Os níveis séricos de AU foram menores no grupo com discinesia quando comparados ao grupo sem discinesia. O mesmo resultado foi encontrado nos níveis de AU de homens e mulheres. A análise multivariada mostrou que níveis mais baixos de ácido úrico foram significativamente associados a ter discinesia (odds ratio [OR] = 0,424; intervalo de confiança (IC) de 95%: 0,221­0,746; p = 0,005). Análises adicionais verificaram que os níveis séricos de AU estão inversamente correlacionados com sintomas depressivos, duração da doença, MDS-UPDRS IV e tempo gasto com discinesia. Uma correlação positiva foi encontrada com a idade de início dos sintomas da DP. CONCLUSõES: O presente estudo fornece um possível papel dos níveis séricos de AU na LID presente em pacientes com DP.

X-Chromosome Association Study in Latin American Cohorts Identifies New Loci in Parkinson Disease.

Sex differences in Parkinson Disease (PD) risk are well-known. However, it is still unclear the role of sex chromosomes in the development and progression of PD. We performed the first X-chromosome Wide Association Study (XWAS) for PD risk in Latin American individuals. We used data from three admixed cohorts: (i) Latin American Research consortium on the GEnetics of Parkinson's Disease (n=1,504) as discover cohort and (ii) Latino cohort from International Parkinson Disease Genomics Consortium (n = 155) and (iii) Bambui Aging cohort (n= 1,442) as replication cohorts. After developing a X-chromosome framework specifically designed for admixed populations, we identified eight linkage disequilibrium regions associated with PD. We fully replicated one of these regions (top variant rs525496; discovery OR [95%CI]: 0.60 [0.478 - 0.77], p = 3.13 × 10 -5 ; replication OR: 0.60 [0.37-0.98], p = 0.04). rs525496 is an expression quantitative trait loci for several genes expressed in brain tissues, including RAB9B, H2BFM, TSMB15B and GLRA4 . We also replicated a previous XWAS finding (rs28602900), showing that this variant is associated with PD in non-European populations. Our results reinforce the importance of including X-chromosome and diverse populations in genetic studies.

Low serum uric acid levels and levodopa-induced dyskinesia in Parkinson's disease / Níveis séricos baixos de ácido úrico e discinesia induzida por levodopa na doença de Parkinson

Abstract Background Levodopa is the most used and effective medication for motor symptoms of Parkinson disease (PD), its long-term use is associated with the appearance of levodopa-induced dyskinesia (LID). Uric acid (UA) is believed to play an important neuroprotective role in PD. Objective To investigate if serum UA levels are related with the presence of LIDs in PD patients. Also, we investigated the associations among UA levels and clinical features of PD. Methods We enrolled 81 PD patients (dyskinesia = 48; no dyskinesia = 33) in the present study. A blood sample was collected to evaluate serum UA levels, clinical evaluation included the following instruments: Montreal Cognitive Assessment (MoCA), Beck Depression Inventory II (BDI-II), MDS-Unified Parkinson's Disease Rating Scale (MDS-UPDRS), Hoehn and Yahr (HY), and the sub-item 4.1 of MDS-UPDRS IV (score ≥ 1). Additional relevant clinical information was obtained by a clinical questionnaire. Results Serum UA levels were lower in the dyskinesia group when compared with the no dyskinesia group. The same result was found in the UA levels of both men and women. The multivariate analysis showed lower uric acid levels were significantly associated with having dyskinesia (odds ratio [OR] = 0.424; 95% confidence interval [CI]: 0.221-0.746; p= 0.005). Additional analysis verified that serum UA levels are inversely correlated with depressive symptoms, disease duration, MDS-UPDRS IV and time spent with dyskinesia. A positive correlation was found with age at onset of PD symptoms. Conclusions The present study provides a possible role of serum UA levels in LID present in PD patients.

Resumo Antecedentes A levodopa é a medicação mais utilizada e eficaz para os sintomas motores da doença de Parkinson (DP); seu uso a longo prazo está associado ao aparecimento de discinesia induzida por levodopa (LID). Acredita-se que o ácido úrico desempenhe um importante papel neuroprotetor na DP. Objetivo Investigar se os níveis séricos de AU estão relacionados com a presença de LID em pacientes com DP. Além disso, investigamos as associações entre os níveis de AU e as características clínicas da DP. Métodos Foram incluídos 81 pacientes com DP (discinesia = 48; sem discinesia = 33) no presente estudo. Uma amostra de sangue foi coletada para avaliar os níveis séricos de AU, a avaliação clínica incluiu os seguintes instrumentos: Avaliação Cognitiva de Montreal (MoCA), Inventário de Depressão de Beck (BDI-II), MDS-Unified Parkinson's Disease Rating Scale (MDS-UPDRS), Hoehn and Yahr (HY) e o subitem 4.1 da MDS-UPDRS IV (escore ≥ 1). Informações clínicas relevantes adicionais foram obtidas por meio de um questionário clínico. Resultados Os níveis séricos de AU foram menores no grupo com discinesia quando comparados ao grupo sem discinesia. O mesmo resultado foi encontrado nos níveis de AU de homens e mulheres. A análise multivariada mostrou que níveis mais baixos de ácido úrico foram significativamente associados a ter discinesia (odds ratio [OR] = 0,424; intervalo de confiança (IC) de 95%: 0,221-0,746; p= 0,005). Análises adicionais verificaram que os níveis séricos de AU estão inversamente correlacionados com sintomas depressivos, duração da doença, MDS-UPDRS IV e tempo gasto com discinesia. Uma correlação positiva foi encontrada com a idade de início dos sintomas da DP. Conclusões O presente estudo fornece um possível papel dos níveis séricos de AU na LID presente em pacientes com DP.

Life-space mobility, balance, and self-efficacy in Parkinson disease: A cross-sectional study.

BACKGROUND: Life-space mobility (LSM) is a mobility measure that assesses the physical and social environments through which people move during their daily lives. OBJECTIVE: To characterize LSM among individuals with Parkinson disease and explore the relationship between LSM, self-efficacy, and balance. DESIGN: A cross-sectional study. SETTINGS: Movement disorder clinic at a teaching hospital. PARTICIPANTS: Eighty-eight participants with Parkinson disease. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: The dependent variable (LSM) was assessed using the Life-Space Assessment (LSA) instrument. Balance evaluation and balance self-efficacy were assessed using the Mini Balance Evaluation Systems Test (Mini-BESTest) and the Activities-Specific Balance Confidence Scale, respectively. Other variables, such as age, disease staging (Hoehn-Yahr staging system), cognition (Montreal Cognitive Assessment), and depressive symptoms (Beck Depression Inventory-II), were also measured. RESULTS: The mean LSA score was 65.2 (SD: 22.8) and mean age was 63.2 years (SD: 10.5 years). Among the 88 patients, 32 (36.4%) were classified as restricted LSM. Age (p = .03), disease severity (p = .02), cognition (p = .02), and motor subtype (p = .006) were associated with more restricted LSM among participants. A multiple linear regression model demonstrated that LSM can be predicted by balance performance (R2  = 0.377; p < .001). CONCLUSION: Age, disease severity, cognition, motor subtype, balance self-efficacy, and balance performance are associated with LSM. Understanding and improving balance and self-efficacy in people with Parkinson disease could facilitate community mobility and promote functional independence and health maintenance.

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.