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INTRODUCTION: Patients with Parkinson's disease (PD) are more likely to suffer from cognitive impairment and dementia than healthy older adults. The aim of this study was to investigate smoking history as a risk factor for cognitive decline in PD. METHOD: One hundred thirty-nine PD patients aged 50 years and older (Hoehn and Yahr = 1-3) were recruited from a clinical database. Global cognitive function was assessed with the Mini-Mental State Examination (MMSE) and smoking history was investigated as part of a standard clinical interview. A multiple linear regression analysis was used to develop a model for predicting participants' MMSE scores from age, education, Hoehn and Yahr stage, disease duration, the number of vascular risk factors and the number of smoking pack-years. RESULTS: The regression model significantly accounted for 22.9% of the variance in MMSE scores. Significant predictors were education (ß = .312, p < .001), age (ß = -.215, p = .013) and total smoking pack-years (ß = -.180, p = .029). In former smokers, the number of years since quitting had no effect on global cognition and there were no significant difference between patients who had quit smoking more than 10 years ago and those who had quit less than 10 years ago, F(1, 63) = 1.72, p = .195. CONCLUSION: Smoking history was associated to global cognitive impairment in PD even in patients who had quit smoking. These results are in line with findings in healthy older adults that have linked smoking to cognitive impairment, global brain atrophy and functional changes. Future studies should consider a broader assessment of cognitive functions.
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Disfunção Cognitiva/epidemiologia , Doença de Parkinson/epidemiologia , Fumar/epidemiologia , Idoso , Estudos de Casos e Controles , Disfunção Cognitiva/diagnóstico , Estudos Transversais , Demência/diagnóstico , Demência/epidemiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Testes Neuropsicológicos , Análise de Regressão , Fatores de Risco , Fumar/efeitos adversos , Abandono do Hábito de Fumar/estatística & dados numéricos , Doenças Vasculares/epidemiologiaRESUMO
OBJECTIVE: To describe the clinical, genetic, and epidemiologic features of hereditary spastic paraplegia (HSP) in Canada and to determine which clinical, radiologic, and genetic factors determine functional outcomes for patients with HSP. METHODS: We conducted a multicenter observational study of patients who met clinical criteria for the diagnosis of HSP in the provinces of Alberta, Ontario, and Quebec from 2012 to 2015. Characteristics of the participants were analyzed using descriptive statistics. The main outcome measure for a subset of the cohort (n = 48) was the Spastic Paraplegia Rating Scale. We also used the SPATAX-EUROSPA disability stage (disability score) to assess disability (n = 65). RESULTS: A total of 526 patients were identified with HSP across the country, and 150 patients had a confirmed genetic diagnosis. Mutations were identified in 15 different genes; the most common were SPAST (SPG4, 48%), ATL1 (SPG3A, 16%), SPG11 (8%), SPG7 (7%), and KIAA0196 (SPG8, 5%). The diagnosis of SPG4 was associated with older age at symptom onset (p = 0.0017). SPG4 and SPG3A were less associated with learning disabilities compared to other subtypes of HSP, and SPG11 was strongly associated with progressive cognitive deficits (odds ratio 87.75, 95% confidence interval 14.04-548.24, p < 0.0001). SPG3A was associated with better functional outcomes compared to other HSP subtypes (p = 0.04) on multivariate analysis. The strongest predictor of significant disability was abnormal brain MRI (p = 0.014). CONCLUSIONS: The most important predictors of disability in our HSP cohort were SPG11 mutations and abnormal brain MRI. Accurate molecular characterization of well-phenotyped cohorts and international collaboration are essential to establish the natural history of these rare neurodegenerative disorders.
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Amyotrophic lateral sclerosis (ALS) is a devastating neurodegenerative disorder characterized by an extensive loss of motor neurons in the primary motor cortex, brainstem, and spinal cord. Genetic studies report a high heritability of ALS. Recently, whole-exome sequencing analysis of familial ALS (FALS) patients allowed the identification of missense variations within the MATR3 gene. MATR3 was previously associated to distal myopathy 2 and encodes for a nuclear matrix and DNA/RNA binding protein that has been shown to interact with TDP43 in an RNA-dependent manner. Here, we assessed the MATR3 mutation frequency in French-Canadian ALS and control individuals (nFALS = 83, sporadic ALS [nSALS] = 164, and ncontrols = 162) and showed that MATR3 mutations were found in 0%, 1.8%, and 0% of FALS, SALS, and controls, respectively. Interestingly, among the mutations identified in SALS, the splicing mutation c.48+1G>T was found to result in the insertion of 24 amino acids in MATR3 protein. These findings further support the role of MATR3 in ALS, and more studies are needed to shed more light on MATR3 proteinopathy.
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Esclerose Lateral Amiotrófica/genética , Estudos de Associação Genética , Mutação , Proteínas Associadas à Matriz Nuclear/genética , Proteínas de Ligação a RNA/genética , Sequência de Bases , Canadá , Proteínas de Ligação a DNA/genética , Exoma/genética , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Dados de Sequência Molecular , Proteínas Associadas à Matriz Nuclear/fisiologia , RNA/metabolismo , Proteínas de Ligação a RNA/fisiologia , Reação em Cadeia da Polimerase Via Transcriptase Reversa , População BrancaRESUMO
Large repeat expansions in the C9orf72 gene were recently reported to be a major cause of familial amyotrophic lateral sclerosis and frontotemporal dementia. Given some of the clinical and pathologic overlap between these 2 diseases and Parkinson's disease, we sought to evaluate the presence of these expansions in a cohort of French-Canadian patients with Parkinson's disease. No pathologic expansion was found in our cohort of patients suggesting that C9orf72 repeat expansions do not play a major role in the pathogenesis of Parkinson's disease.
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Expansão das Repetições de DNA/genética , Doença de Parkinson/diagnóstico , Doença de Parkinson/genética , Proteínas/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Proteína C9orf72 , Canadá/epidemiologia , Estudos de Coortes , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Doença de Parkinson/epidemiologia , Adulto JovemRESUMO
The utility of the Mattis Dementia Rating Scale 2 (MDRS-2) in screening for dementia in Parkinson disease (PD) is well documented. However, little is known about its sensitivity to mild cognitive impairment in PD (PD-MCI). This study sought to document the validity of the MDRS-2 for diagnoses of PD-MCI and dementia in PD (PDD). Twenty-two healthy controls (HCs), 22 PD-MCI, and 16 PDD were compared on each MDRS-2 subscales and MDRS-2 total standard scores. Patients with PDD performed significantly worse than the other groups (all Ps < .05) on the MDRS-2 total and on all subscales, except attention. PD-MCI had significant lower scores than HCs on the MDRS-2 total and on initiation/perseveration and memory subscales. The optimal cutoff score for PD-MCI diagnosis was ≤ 140/144 and ≤ 132/144 for PDD. These findings suggest that MDRS-2 is a useful tool to identify dementia but that there might be a ceiling effect in the MDRS-2 cutoff score to diagnose MCI in PD.
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Disfunção Cognitiva/diagnóstico , Demência/diagnóstico , Testes Neuropsicológicos , Doença de Parkinson/diagnóstico , Idoso , Idoso de 80 Anos ou mais , Atenção , Disfunção Cognitiva/complicações , Disfunção Cognitiva/psicologia , Estudos Transversais , Demência/complicações , Demência/psicologia , Feminino , Humanos , Masculino , Memória , Pessoa de Meia-Idade , Escalas de Graduação Psiquiátrica , Reprodutibilidade dos Testes , Sensibilidade e EspecificidadeRESUMO
OBJECTIVE: To analyze the ataxin 2 (ATXN2) CAG repeat size in a cohort of patients with amyotrophic lateral sclerosis (ALS) and healthy controls. Large (CAG)(n) alleles of the ATXN2 gene (27-33 repeats) were recently reported to be associated with an increased risk of ALS. DESIGN: Case-control study. SETTING: France and Quebec, Canada. PARTICIPANTS: A total of 556 case patients with ALS and 471 healthy controls; both groups of participants are of French or French-Canadian origin. RESULTS: We observed a significant association between ATXN2 high-length alleles (≥29 CAG repeats) and ALS in French and French-Canadian ALS populations. Furthermore, we identified spinocerebellar ataxia type 2-pathogenic polyglutamine expansions (≥32 CAG repeats) in both familial and sporadic ALS cases. CONCLUSIONS: Altogether, our findings support ATXN2 high-length repeats as a risk factor for ALS and further indicate a genetic link between spinocerebellar ataxia type 2 and ALS.
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Esclerose Lateral Amiotrófica/genética , Predisposição Genética para Doença/genética , Proteínas do Tecido Nervoso/genética , Expansão das Repetições de Trinucleotídeos/genética , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Esclerose Lateral Amiotrófica/epidemiologia , Esclerose Lateral Amiotrófica/etnologia , Ataxinas , Estudos de Casos e Controles , Estudos de Coortes , Feminino , Ligação Genética , Predisposição Genética para Doença/epidemiologia , Predisposição Genética para Doença/etnologia , Humanos , Masculino , Pessoa de Meia-Idade , Fatores de Risco , Ataxias Espinocerebelares/epidemiologia , Ataxias Espinocerebelares/etnologia , Ataxias Espinocerebelares/genética , Adulto JovemRESUMO
Identifying patients at higher risk of developing dementia is important. The usefulness of the Mattis Dementia Rating scale-Second Edition (MDRS-2) to detect and differentiate between patients with amnestic mild cognitive impairment (A-MCI), Parkinson's disease and MCI (PD-MCI), PD with dementia (PDD), and Alzheimer's disease (AD) was investigated. In all, 22 healthy controls (HC), 22 A-MCI, 22 PD-MCI, 16 PDD, and 22 AD patients were evaluated using an extensive neuropsychological battery, including the MDRS-2. The MDRS-2 total standardized score detected all groups of patients. The dementia groups performed worse than HC on the 5 MDRS-2 subscales. Alzheimer's disease patients scored higher than PDD on MDRS-2 conceptualization and lower on memory. Healthy controls were better than PD-MCI on MDRS-2 initiation/perseveration and memory and better than A-MCI on memory. No difference was found between the MCI groups. The MDRS-2 is a suitable short scale for MCI and dementia screening but is not specific enough to differentiate between A-MCI and PD-MCI.
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Transtornos Cognitivos/diagnóstico , Demência/diagnóstico , Testes Neuropsicológicos , Idoso , Doença de Alzheimer/diagnóstico , Estudos de Casos e Controles , Estudos Transversais , Feminino , Humanos , Masculino , Memória , Transtornos da Memória/diagnóstico , Pessoa de Meia-Idade , Testes Neuropsicológicos/normas , Índice de Gravidade de DoençaAssuntos
Química Encefálica/genética , Proteínas de Ligação a DNA/genética , Predisposição Genética para Doença/genética , Mutação/genética , Doença de Parkinson/etnologia , Doença de Parkinson/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Encéfalo/metabolismo , Encéfalo/patologia , Encéfalo/fisiopatologia , Análise Mutacional de DNA , Feminino , Frequência do Gene , Marcadores Genéticos , Testes Genéticos , Humanos , Corpos de Lewy/metabolismo , Corpos de Lewy/patologia , Masculino , Pessoa de Meia-Idade , Neurônios/metabolismo , Neurônios/patologia , Grupos Populacionais/genética , QuebequeRESUMO
BACKGROUND: An old founder mutation (G2019S) was found with high frequency in the North African Arabs (30%) and Ashkenazi Jews (18% ). OBJECTIVE: Demonstrate if mutations in the LRRK2 gene are a significant cause of Parkinson's disease (PD) in the French-Canadian founder population. METHODS: Cases were recruited through a designated movement disorder clinic in Quebec City. Every index case had to meet the Ward and Gibb criteria for PD. Controls consisted of a non-disease group of similar age and ethnicity as the cases. Exons 31 and 41 of LRRK2 were amplified by PCR with intronic primers in all 125 PD cases and directly sequenced on an ABI 3700 sequencer. Six single nucleotide polymorphism were typed in 125 PD cases and 95 normal controls. Associations between unrelated cases and matched controls were analyzed. Single marker analysis and haplotype association tests were performed. RESULTS: Sequencing analysis did not reveal any reported or novel mutations in exons 31 and 41 of LRRK2. The G2019S mutation as well as mutations affecting amino acid 1441 were absent in the 125 patients. The case-control association study performed to detect the presence of a common variant in LRRK2 did not provide any positive signal. Single-marker and haplotype analyses systematically gave non-significant P values. CONCLUSIONS: We performed a case-control association study in 125 French-Canadian (FC) patients with PD and 95 FC controls and found that common variants in LRRK2 are unlikely to be a significant cause of late-onset PD in this founder population.
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Predisposição Genética para Doença/genética , Mutação/genética , Doença de Parkinson/genética , Proteínas Serina-Treonina Quinases/genética , Adulto , Idade de Início , Idoso , Estudos de Casos e Controles , Análise Mutacional de DNA , Éxons/genética , Feminino , Efeito Fundador , Marcadores Genéticos/genética , Testes Genéticos , Genótipo , Haplótipos , Humanos , Serina-Treonina Proteína Quinase-2 com Repetições Ricas em Leucina , Masculino , Pessoa de Meia-Idade , Doença de Parkinson/diagnóstico , Doença de Parkinson/epidemiologia , Polimorfismo de Nucleotídeo Único/genética , Quebeque/epidemiologia , População Branca/etnologia , População Branca/genéticaRESUMO
Vallerand et al. (2003) have proposed that individuals can have two distinct types of passion toward an activity. Harmonious passion, an internal force leading one to choose to engage in the activity, is proposed to be associated with positive consequences. Obsessive passion, an internal pressure forcing one to engage in an activity, is posited to be associated with negative consequences. The present study sought to determine the role of the two types of passion in various cognitive and affective states associated with dependence and problems with gambling. Participants (n = 412) were recruited at the Montréal Casino and given a questionnaire measuring passion toward gambling, as well as consequences associated with dependence and problem gambling. Results showed that obsessive passion for gambling predicted poorer vitality and concentration in daily tasks, as well as increased rumination, anxiety, negative mood, guilt, and problem gambling. These relations were not found for harmonious passion for gambling. Results are discussed in light of the motivational approach to passion (Vallerand et al., 2003).
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Comportamento Aditivo/psicologia , Emoções , Jogo de Azar/psicologia , Motivação , Análise de Variância , Canadá , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Inquéritos e QuestionáriosRESUMO
Vallerand and his colleagues (Vallerand & Blanchard, 1999; Vallerand, Blanchard, Koestner, & Gagné, 2001) have recently proposed a new concept of passion. According to these authors, passion refers to a strong inclination toward an activity that we like, find important, and in which we invest time. Vallerand et al. have identified two types of passion: obsessive and harmonious. Obsessive passion refers to an internal pressure that forces an individual to engage in the activity. Harmonious passion, on the other hand, refers to an internal force that leads an individual to choose freely to engage in an activity. While obsessive passion has been shown in some circumstances to lead to negative psychological and physical consequences, harmonious passion generally leads to positive psychological and physical consequences. The purpose of the present research was to validate a measure of passion toward gambling: the Gambling Passion Scale (GPS). The GPS consists of two subscales (obsessive passion and harmonious passion) comprising five items each. Results from two studies involving a total of 340 participants revealed satisfactory internal consistency and temporal stability indices, as well as a two-factor structure supported by exploratory and confirmatory factor analyses. Finally, a series of partial correlational anaylses between the two subscales and scales assessing behavioral measures related to gambling supported the construct validity of the GPS. The present results suggest that the GPS is a useful scale for research on gambling.