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Jacques Montplaisir - One of the best experts on this subject based on the ideXlab platform.

  • Pareidolias and cognition in isolated REM sleep Behavior Disorder.
    Parkinsonism & Related Disorders, 2020
    Co-Authors: Lucy Honeycutt, Jean-françois Gagnon, Amélie Pelletier, Jessie De Roy, Jacques Montplaisir, Ronald B. Postuma
    Abstract:

    Abstract Background Though visual illusions and hallucinations are common in dementia with Lewy bodies (DLB) and Parkinson's disease (PD), they are not typically observed clinically in prodromal stages, including isolated REM sleep Behavior Disorder (iRBD). False-noise errors on the pareidolia test (seeing faces when none are present) may be an effective measure of susceptibility to future hallucinations in iRBD. Methods One hundred patients with iRBD underwent the 20-image pareidolia test. Clinical markers were assessed and a neuropsychological battery was administered. An exploratory analysis on the impact of pareidolic errors on phenoconversion was also performed. Results In our cohort, 17 patients (17%) made false-noise pareidolic errors. These patients had significantly lower total Montreal Cognitive Assesment (MoCA) scores (26.7 ± 2.3 vs. 24.4 ± 2.6, B = −1.88, 95% CI: [-3.17, −0.59]), with lower subcomponent MoCA scores on memory and visuospatial-executive sections. Pareidolic errors were also associated with lower visuospatial, attention/executive, and memory scores on the neuropsychological tests. Furthermore, after 1.6 years follow-up, 3/16 (19%) patients making pareidolic errors had phenoconverted at time of publication compared to 6/71 (8%) patients who did not make errors. Conclusion Pareidolic errors in patients with iRBD are associated with poorer overall cognition and may indicate higher risk of DLB.

  • smpd1 variants do not have a major role in rem sleep Behavior Disorder
    medRxiv, 2020
    Co-Authors: Uladzislau Rudakou, Isabelle Arnulf, Jacques Montplaisir, Jennifer Ruskey, Naomi C Futhey, Lynne Krohn, Karl Heilbron, Paul Cannon, Armaghan Alam, Jean-françois Gagnon
    Abstract:

    Mutations in the sphingomyelin phosphodiesterase 1 (SMPD1) gene were reported to be associated with Parkinson disease (PD) and dementia with Lewy bodies (DLB). The majority of patients with isolated rapid eye movement sleep Behavior Disorder (iRBD) develop PD or DLB later in life, suggesting that iRBD is a prodromal phase of these two conditions. In the current study we aimed to evaluate the role of SMPD1 variants in iRBD. SMPD1 and its untranslated regions were sequenced using targeted next-generation sequencing in 959 iRBD patients and 1,287 controls from European descent. Logistic regression adjusted for sex and age showed no significant associations with two common variants and iRBD (rs1050239 and rs8164). The frequency of all rare nonsynonymous SMPD1 variants (minor allele frequency <1%) was found to be twice as high in cases than in controls (1.46% vs. 0.70%, Fisher's exact test p=0.09) but there was no statistically significant burden (p=0.64). Our study reports no statistically significant association of SMPD1 variants and iRBD. It is hence unlikely that SMPD1 plays a major role in iRBD.

  • validation of the mds research criteria for prodromal parkinson s disease longitudinal assessment in a rem sleep Behavior Disorder rbd cohort
    Movement Disorders, 2017
    Co-Authors: Jean-françois Gagnon, Amélie Pelletier, Jacques Montplaisir, Seyedmohammad Fereshtehnejad, Daniela Berg, Ronald B. Postuma
    Abstract:

    Background: Recently, the International Parkinson and Movement Disorder Society introduced the prodromal criteria for PD. Objectives Our study aimed to examine diagnostic accuracy of the criteria as well as the independence of prodromal markers to predict conversion to PD or dementia with Lewy bodies. Methods: This prospective cohort study was performed on 121 individuals with rapid eye movement sleep Behavior Disorder who were followed annually for 1 to 12 years. Using data from a comprehensive panel of prodromal markers, likelihood ratio and post-test probability of the criteria were calculated at baseline and during each follow-up visit. Results: Forty-eight (39.7%) individuals with rapid eye movement sleep Behavior Disorder converted to PD/dementia with Lewy bodies. The prodromal criteria had 81.3% sensitivity and 67.9% specificity for conversion to PD/dementia with Lewy bodies at 4-year follow-up. One year before conversion, sensitivity was 100%. The criteria predicted dementia with Lewy bodies with even higher accuracy than PD without dementia at onset. Those who met the threshold of prodromal criteria at baseline had significantly more rapid conversion into a neurodegenerative state (4.8 vs. 9.1 years; P < 0.001). Pair-wise combinations of different prodromal markers showed that markers were independent of one another. Conclusion: The prodromal criteria are a promising tool for predicting incidence of PD/dementia with Lewy bodies and conversion time in a rapid eye movement sleep Behavior Disorder cohort, with high sensitivity and high specificity with long follow-up. Prodromal markers influence the overall likelihood ratio independently, allowing them to be reliably multiplied. Defining additional markers with high likelihood ratio, further studies with longitudinal assessment and testing thresholds in different target populations will improve the criteria. © 2017 International Parkinson and Movement Disorder Society

  • The dementia-associated APOE ε4 allele is not associated with rapid eye movement sleep Behavior Disorder
    Neurobiology of Aging, 2017
    Co-Authors: Gan-or Ziv, Isabelle Arnulf, Jacques Montplaisir, Birgit Högl, Yves Dauvilliers, Ambra Stefani, Judes Poirier, Simon Warby, Stephanie Strong, Christelle Charley Monaca
    Abstract:

    The present study aimed to examine whether the APOE ε4 allele, associated with dementia with Lewy bodies (DLB), and possibly with dementia in Parkinson's disease (PD), is also associated with idiopathic rapid eye movement sleep Behavior Disorder (RBD). Two single nucleotide polymorphisms, rs429358 and rs7412, were genotyped in RBD patients (n = 480) and in controls (n = 823). APOE ε4 allele frequency was 0.14 among RBD patients and 0.13 among controls (OR = 1.11, 95% CI: 0.88-1.40, p = 0.41). APOE ε4 allele frequencies were similar in those who converted to DLB (0.14) and those who converted to Parkinson's disease (0.12) or multiple system atrophy (0.14, p = 1.0). The APOE ε4 allele is neither a risk factor for RBD nor it is associated with conversion from RBD to DLB or other synucleinopathies.

  • The role of the melanoma gene MC1R in Parkinson disease and REM sleep Behavior Disorder
    Neurobiology of Aging, 2016
    Co-Authors: Ziv Gan-or, Jacques Montplaisir, Amirthagowri Ambalavanan, Cynthia Bourassa, Stephanie Strong, Noreen Mohsin, Simon Girard, Victoria Mallett, Sandra Laurent, Michel Boivin
    Abstract:

    The MC1R gene, suggested to be involved in Parkinson disease (PD) and melanoma, was sequenced in PD patients (n = 539) and controls (n = 265) from New York, and PD patients (n = 551), rapid eye movement sleep Behavior Disorder (RBD) patients (n = 351), and controls (n = 956) of European ancestry. Sixty-eight MC1R variants were identified, including 7 common variants with frequency > 0.01. None of the common variants was associated with PD or RBD in the different regression models. In a meta-analysis with fixed-effect model, the p.R160W variant was associated with an increased risk for PD (odds ratio = 1.22, 95% confidence interval = 1.02-1.47, p = 0.03) but with significant heterogeneity (p = 0.048). Removing one study that introduced the heterogeneity resulted in nonsignificant association (odds ratio = 1.11, 95% confidence interval, 0.92-1.35, p = 0.27, heterogeneity p = 0.57). Rare variants had similar frequencies in patients and controls (10.54% and 10.15%, respectively, p = 0.75), and no cumulative effect of carrying more than one MC1R variant was found. The present study does not support a role for the MC1R p.R160W and other variants in susceptibility for PD or RBD.

Ronald B. Postuma - One of the best experts on this subject based on the ideXlab platform.

  • Pareidolias and cognition in isolated REM sleep Behavior Disorder.
    Parkinsonism & Related Disorders, 2020
    Co-Authors: Lucy Honeycutt, Jean-françois Gagnon, Amélie Pelletier, Jessie De Roy, Jacques Montplaisir, Ronald B. Postuma
    Abstract:

    Abstract Background Though visual illusions and hallucinations are common in dementia with Lewy bodies (DLB) and Parkinson's disease (PD), they are not typically observed clinically in prodromal stages, including isolated REM sleep Behavior Disorder (iRBD). False-noise errors on the pareidolia test (seeing faces when none are present) may be an effective measure of susceptibility to future hallucinations in iRBD. Methods One hundred patients with iRBD underwent the 20-image pareidolia test. Clinical markers were assessed and a neuropsychological battery was administered. An exploratory analysis on the impact of pareidolic errors on phenoconversion was also performed. Results In our cohort, 17 patients (17%) made false-noise pareidolic errors. These patients had significantly lower total Montreal Cognitive Assesment (MoCA) scores (26.7 ± 2.3 vs. 24.4 ± 2.6, B = −1.88, 95% CI: [-3.17, −0.59]), with lower subcomponent MoCA scores on memory and visuospatial-executive sections. Pareidolic errors were also associated with lower visuospatial, attention/executive, and memory scores on the neuropsychological tests. Furthermore, after 1.6 years follow-up, 3/16 (19%) patients making pareidolic errors had phenoconverted at time of publication compared to 6/71 (8%) patients who did not make errors. Conclusion Pareidolic errors in patients with iRBD are associated with poorer overall cognition and may indicate higher risk of DLB.

  • validation of the mds research criteria for prodromal parkinson s disease longitudinal assessment in a rem sleep Behavior Disorder rbd cohort
    Movement Disorders, 2017
    Co-Authors: Jean-françois Gagnon, Amélie Pelletier, Jacques Montplaisir, Seyedmohammad Fereshtehnejad, Daniela Berg, Ronald B. Postuma
    Abstract:

    Background: Recently, the International Parkinson and Movement Disorder Society introduced the prodromal criteria for PD. Objectives Our study aimed to examine diagnostic accuracy of the criteria as well as the independence of prodromal markers to predict conversion to PD or dementia with Lewy bodies. Methods: This prospective cohort study was performed on 121 individuals with rapid eye movement sleep Behavior Disorder who were followed annually for 1 to 12 years. Using data from a comprehensive panel of prodromal markers, likelihood ratio and post-test probability of the criteria were calculated at baseline and during each follow-up visit. Results: Forty-eight (39.7%) individuals with rapid eye movement sleep Behavior Disorder converted to PD/dementia with Lewy bodies. The prodromal criteria had 81.3% sensitivity and 67.9% specificity for conversion to PD/dementia with Lewy bodies at 4-year follow-up. One year before conversion, sensitivity was 100%. The criteria predicted dementia with Lewy bodies with even higher accuracy than PD without dementia at onset. Those who met the threshold of prodromal criteria at baseline had significantly more rapid conversion into a neurodegenerative state (4.8 vs. 9.1 years; P < 0.001). Pair-wise combinations of different prodromal markers showed that markers were independent of one another. Conclusion: The prodromal criteria are a promising tool for predicting incidence of PD/dementia with Lewy bodies and conversion time in a rapid eye movement sleep Behavior Disorder cohort, with high sensitivity and high specificity with long follow-up. Prodromal markers influence the overall likelihood ratio independently, allowing them to be reliably multiplied. Defining additional markers with high likelihood ratio, further studies with longitudinal assessment and testing thresholds in different target populations will improve the criteria. © 2017 International Parkinson and Movement Disorder Society

  • longitudinal changes in cognition in early parkinson s disease patients with rem sleep Behavior Disorder
    Parkinsonism & Related Disorders, 2016
    Co-Authors: Lama M Chahine, Ronald B. Postuma, W H Oertel, A Iranzo, Sharon X Xie, Tanya Simuni, Baochan Tran, Amy W Amara, Christi Scordia, Michelle E Fullard
    Abstract:

    Abstract Introduction Cognitive decline is common in Parkinson's disease (PD), and identifying patients at highest risk for it is essential. We aimed to examine the effect of possible REM sleep Behavior Disorder (pRBD) on rate of cognitive decline in early PD, for both global cognition and in specific cognitive domains. Methods Parkinson's Progression Markers Initiative (PPMI) is a multi-site, international study of PD patients untreated at enrollment. pRBD was assessed with the REM sleep Behavior Disorder questionnaire (RBDSQ). Global cognition was assessed at baseline and annually using the Montreal Cognitive Assessment (MoCA) and a cognitive battery. Linear mixed effects models were used to examine the relationship between pRBD (RBDSQ ≥ 6) and rate of change in cognitive variables. Age, sex, years of education, and baseline motor and cognitive scores were included as covariates. Results The baseline sample consisted of 423 individuals with PD, mean age 61.7 years and 65.5% male. Data was available on 389, 366, and 196 participants at 1-year, 2-year, and 3-year follow-up respectively. Possible RBD occurred in 108 (25.5%) at baseline. In multivariate analyses, baseline RBD was associated with greater annual rate of decline in MoCA score (β = −0.34, 95%CI −0.54, −0.13, p  Conclusions Possible RBD is common in early PD and predicts future cognitive decline, particularly in attention and memory domains.

  • Risk Factor Profile in Parkinson’s Disease Subtype with REM Sleep Behavior Disorder
    Journal of Parkinson's disease, 2016
    Co-Authors: Marie Jacobs, Jean-françois Gagnon, Amélie Pelletier, Ronald B. Postuma, Yves Dauvilliers, Stuart J Mccarter, Silvia Rios Romenets, Erik St Louis, Mahmoud Cherif
    Abstract:

    BACKGROUND: Numerous large-scale studies have found diverse risk factors for Parkinson's disease (PD), including caffeine non-use, non-smoking, head injury, pesticide exposure, and family history. These studies assessed risk factors for PD overall; however, PD is a heterogeneous condition. One of the strongest identifiers of prognosis and disease subtype is the co-occurrence of rapid eye movement sleep Behavior Disorder (RBD).In previous studies, idiopathic RBD was associated with a different risk factor profile from PD and dementia with Lewy bodies, suggesting that the PD-RBD subtype may also have a different risk factor profile. OBJECTIVE: To define risk factors for PD in patients with or without associated RBD. METHODS: In a questionnaire, we assessed risk factors for PD, including demographic, medical, environmental, and lifestyle variables of 189 PD patients with or without associated polysomnography-confirmed RBD. The risk profile of patients with vs. without RBD was assessed with logistic regression, adjusting for age, sex, and disease duration. RESULTS: PD-RBD patients were more likely to have been a welder (OR = 3.11 (1.05-9.223), and to have been regular smokers (OR = 1.96 (1.04-3.68)). There were no differences in use of caffeine or alcohol, other occupations, pesticide exposure, rural living, or well water use. Patients with RBD had a higher prevalence of the combined family history of both dementia and parkinsonism (13.3% vs. 5.5% , OR = 3.28 (1.07-10.0). CONCLUSION: The RBD-specific subtype of PD may also have a different risk factor profile.

  • GBA mutations are associated with Rapid Eye Movement Sleep Behavior Disorder
    Annals of clinical and translational neurology, 2015
    Co-Authors: Ziv Gan-or, Isabelle Arnulf, Jean-françois Gagnon, Ronald B. Postuma, Anat Mirelman, Yves Dauvilliers, Alex Desautels, Claire S Leblond, Anat Bar-shira, Birgit Frauscher
    Abstract:

    Rapid eye movement sleep Behavior Disorder and GBA mutations are both associated with Parkinson's disease. The GBA gene was sequenced in idiopathic rapid eye movement sleep Behavior Disorder patients (n = 265), and compared to controls (n = 2240). Rapid eye movement sleep Behavior Disorder questionnaire was performed in an independent Parkinson's disease cohort (n = 120). GBA mutations carriers had an OR of 6.24 (10.2% in patients vs. 1.8% in controls, P 

Jean-françois Gagnon - One of the best experts on this subject based on the ideXlab platform.

  • Pareidolias and cognition in isolated REM sleep Behavior Disorder.
    Parkinsonism & Related Disorders, 2020
    Co-Authors: Lucy Honeycutt, Jean-françois Gagnon, Amélie Pelletier, Jessie De Roy, Jacques Montplaisir, Ronald B. Postuma
    Abstract:

    Abstract Background Though visual illusions and hallucinations are common in dementia with Lewy bodies (DLB) and Parkinson's disease (PD), they are not typically observed clinically in prodromal stages, including isolated REM sleep Behavior Disorder (iRBD). False-noise errors on the pareidolia test (seeing faces when none are present) may be an effective measure of susceptibility to future hallucinations in iRBD. Methods One hundred patients with iRBD underwent the 20-image pareidolia test. Clinical markers were assessed and a neuropsychological battery was administered. An exploratory analysis on the impact of pareidolic errors on phenoconversion was also performed. Results In our cohort, 17 patients (17%) made false-noise pareidolic errors. These patients had significantly lower total Montreal Cognitive Assesment (MoCA) scores (26.7 ± 2.3 vs. 24.4 ± 2.6, B = −1.88, 95% CI: [-3.17, −0.59]), with lower subcomponent MoCA scores on memory and visuospatial-executive sections. Pareidolic errors were also associated with lower visuospatial, attention/executive, and memory scores on the neuropsychological tests. Furthermore, after 1.6 years follow-up, 3/16 (19%) patients making pareidolic errors had phenoconverted at time of publication compared to 6/71 (8%) patients who did not make errors. Conclusion Pareidolic errors in patients with iRBD are associated with poorer overall cognition and may indicate higher risk of DLB.

  • smpd1 variants do not have a major role in rem sleep Behavior Disorder
    medRxiv, 2020
    Co-Authors: Uladzislau Rudakou, Isabelle Arnulf, Jacques Montplaisir, Jennifer Ruskey, Naomi C Futhey, Lynne Krohn, Karl Heilbron, Paul Cannon, Armaghan Alam, Jean-françois Gagnon
    Abstract:

    Mutations in the sphingomyelin phosphodiesterase 1 (SMPD1) gene were reported to be associated with Parkinson disease (PD) and dementia with Lewy bodies (DLB). The majority of patients with isolated rapid eye movement sleep Behavior Disorder (iRBD) develop PD or DLB later in life, suggesting that iRBD is a prodromal phase of these two conditions. In the current study we aimed to evaluate the role of SMPD1 variants in iRBD. SMPD1 and its untranslated regions were sequenced using targeted next-generation sequencing in 959 iRBD patients and 1,287 controls from European descent. Logistic regression adjusted for sex and age showed no significant associations with two common variants and iRBD (rs1050239 and rs8164). The frequency of all rare nonsynonymous SMPD1 variants (minor allele frequency <1%) was found to be twice as high in cases than in controls (1.46% vs. 0.70%, Fisher's exact test p=0.09) but there was no statistically significant burden (p=0.64). Our study reports no statistically significant association of SMPD1 variants and iRBD. It is hence unlikely that SMPD1 plays a major role in iRBD.

  • LRRK2 protective haplotype and full sequencing study in REM sleep Behavior Disorder
    Parkinsonism and Related Disorders, 2018
    Co-Authors: Bouchra Ouled Amar Bencheikh, Isabelle Arnulf, Jean-françois Gagnon, Birgit Högl, Yves Dauvilliers, Jennifer Ruskey, Dan Spiegelman, Christelle Charley Monaca, Valérie Cochen De Cock, Ambra Stefani
    Abstract:

    BACKGROUND: Individuals with rapid eye movement (REM)-sleep Behavior Disorder (RBD) are likely to progress to synucleinopathies, mainly Parkinson's disease (PD), dementia with Lewy-bodies (DLB) and multiple system atrophy (MSA). The genetics of RBD only partially overlaps with PD and DLB, and the role of LRRK2 variants in risk for RBD is still not clear. METHODS: The full coding sequence, exon-intron boundaries and 5' and 3' untranslated regions of LRRK2 were sequenced using targeted next-generation sequencing. A total of 350 RBD patients and 869 controls were sequenced, and regression and burden models were used to examine the association between LRRK2 variants and RBD. RESULTS: No pathogenic mutations that are known to cause PD were identified in RBD patients. The p.N551K-p.R1398H-p.K1423K haplotype was associated with a reduced risk for RBD (OR = 0.66, 95% CI 0.44-0.98, p = 0.0055 for the tagging p.N551K substitution). A common variant, p.S1647T, was nominally associated with risk for RBD (OR = 1.28, 95% CI 1.05-1.56, p = 0.029). Burden analysis identified associations with domains and exons that were derived by the variants of the protective haplotype, and no burden of other rare variants was identified. CONCLUSIONS: Carriers of the LRRK2 p.N551K-p.R1398H-p.K1423K haplotype have a reduced risk for developing RBD, yet PD-causing mutations probably have minor or no role in RBD. Additional work is needed to confirm these results and to identify the mechanism associated with reduced risk for RBD.

  • validation of the mds research criteria for prodromal parkinson s disease longitudinal assessment in a rem sleep Behavior Disorder rbd cohort
    Movement Disorders, 2017
    Co-Authors: Jean-françois Gagnon, Amélie Pelletier, Jacques Montplaisir, Seyedmohammad Fereshtehnejad, Daniela Berg, Ronald B. Postuma
    Abstract:

    Background: Recently, the International Parkinson and Movement Disorder Society introduced the prodromal criteria for PD. Objectives Our study aimed to examine diagnostic accuracy of the criteria as well as the independence of prodromal markers to predict conversion to PD or dementia with Lewy bodies. Methods: This prospective cohort study was performed on 121 individuals with rapid eye movement sleep Behavior Disorder who were followed annually for 1 to 12 years. Using data from a comprehensive panel of prodromal markers, likelihood ratio and post-test probability of the criteria were calculated at baseline and during each follow-up visit. Results: Forty-eight (39.7%) individuals with rapid eye movement sleep Behavior Disorder converted to PD/dementia with Lewy bodies. The prodromal criteria had 81.3% sensitivity and 67.9% specificity for conversion to PD/dementia with Lewy bodies at 4-year follow-up. One year before conversion, sensitivity was 100%. The criteria predicted dementia with Lewy bodies with even higher accuracy than PD without dementia at onset. Those who met the threshold of prodromal criteria at baseline had significantly more rapid conversion into a neurodegenerative state (4.8 vs. 9.1 years; P < 0.001). Pair-wise combinations of different prodromal markers showed that markers were independent of one another. Conclusion: The prodromal criteria are a promising tool for predicting incidence of PD/dementia with Lewy bodies and conversion time in a rapid eye movement sleep Behavior Disorder cohort, with high sensitivity and high specificity with long follow-up. Prodromal markers influence the overall likelihood ratio independently, allowing them to be reliably multiplied. Defining additional markers with high likelihood ratio, further studies with longitudinal assessment and testing thresholds in different target populations will improve the criteria. © 2017 International Parkinson and Movement Disorder Society

  • Risk Factor Profile in Parkinson’s Disease Subtype with REM Sleep Behavior Disorder
    Journal of Parkinson's disease, 2016
    Co-Authors: Marie Jacobs, Jean-françois Gagnon, Amélie Pelletier, Ronald B. Postuma, Yves Dauvilliers, Stuart J Mccarter, Silvia Rios Romenets, Erik St Louis, Mahmoud Cherif
    Abstract:

    BACKGROUND: Numerous large-scale studies have found diverse risk factors for Parkinson's disease (PD), including caffeine non-use, non-smoking, head injury, pesticide exposure, and family history. These studies assessed risk factors for PD overall; however, PD is a heterogeneous condition. One of the strongest identifiers of prognosis and disease subtype is the co-occurrence of rapid eye movement sleep Behavior Disorder (RBD).In previous studies, idiopathic RBD was associated with a different risk factor profile from PD and dementia with Lewy bodies, suggesting that the PD-RBD subtype may also have a different risk factor profile. OBJECTIVE: To define risk factors for PD in patients with or without associated RBD. METHODS: In a questionnaire, we assessed risk factors for PD, including demographic, medical, environmental, and lifestyle variables of 189 PD patients with or without associated polysomnography-confirmed RBD. The risk profile of patients with vs. without RBD was assessed with logistic regression, adjusting for age, sex, and disease duration. RESULTS: PD-RBD patients were more likely to have been a welder (OR = 3.11 (1.05-9.223), and to have been regular smokers (OR = 1.96 (1.04-3.68)). There were no differences in use of caffeine or alcohol, other occupations, pesticide exposure, rural living, or well water use. Patients with RBD had a higher prevalence of the combined family history of both dementia and parkinsonism (13.3% vs. 5.5% , OR = 3.28 (1.07-10.0). CONCLUSION: The RBD-specific subtype of PD may also have a different risk factor profile.

Isabelle Arnulf - One of the best experts on this subject based on the ideXlab platform.

  • smpd1 variants do not have a major role in rem sleep Behavior Disorder
    medRxiv, 2020
    Co-Authors: Uladzislau Rudakou, Isabelle Arnulf, Jacques Montplaisir, Jennifer Ruskey, Naomi C Futhey, Lynne Krohn, Karl Heilbron, Paul Cannon, Armaghan Alam, Jean-françois Gagnon
    Abstract:

    Mutations in the sphingomyelin phosphodiesterase 1 (SMPD1) gene were reported to be associated with Parkinson disease (PD) and dementia with Lewy bodies (DLB). The majority of patients with isolated rapid eye movement sleep Behavior Disorder (iRBD) develop PD or DLB later in life, suggesting that iRBD is a prodromal phase of these two conditions. In the current study we aimed to evaluate the role of SMPD1 variants in iRBD. SMPD1 and its untranslated regions were sequenced using targeted next-generation sequencing in 959 iRBD patients and 1,287 controls from European descent. Logistic regression adjusted for sex and age showed no significant associations with two common variants and iRBD (rs1050239 and rs8164). The frequency of all rare nonsynonymous SMPD1 variants (minor allele frequency <1%) was found to be twice as high in cases than in controls (1.46% vs. 0.70%, Fisher's exact test p=0.09) but there was no statistically significant burden (p=0.64). Our study reports no statistically significant association of SMPD1 variants and iRBD. It is hence unlikely that SMPD1 plays a major role in iRBD.

  • LRRK2 protective haplotype and full sequencing study in REM sleep Behavior Disorder
    Parkinsonism and Related Disorders, 2018
    Co-Authors: Bouchra Ouled Amar Bencheikh, Isabelle Arnulf, Jean-françois Gagnon, Birgit Högl, Yves Dauvilliers, Jennifer Ruskey, Dan Spiegelman, Christelle Charley Monaca, Valérie Cochen De Cock, Ambra Stefani
    Abstract:

    BACKGROUND: Individuals with rapid eye movement (REM)-sleep Behavior Disorder (RBD) are likely to progress to synucleinopathies, mainly Parkinson's disease (PD), dementia with Lewy-bodies (DLB) and multiple system atrophy (MSA). The genetics of RBD only partially overlaps with PD and DLB, and the role of LRRK2 variants in risk for RBD is still not clear. METHODS: The full coding sequence, exon-intron boundaries and 5' and 3' untranslated regions of LRRK2 were sequenced using targeted next-generation sequencing. A total of 350 RBD patients and 869 controls were sequenced, and regression and burden models were used to examine the association between LRRK2 variants and RBD. RESULTS: No pathogenic mutations that are known to cause PD were identified in RBD patients. The p.N551K-p.R1398H-p.K1423K haplotype was associated with a reduced risk for RBD (OR = 0.66, 95% CI 0.44-0.98, p = 0.0055 for the tagging p.N551K substitution). A common variant, p.S1647T, was nominally associated with risk for RBD (OR = 1.28, 95% CI 1.05-1.56, p = 0.029). Burden analysis identified associations with domains and exons that were derived by the variants of the protective haplotype, and no burden of other rare variants was identified. CONCLUSIONS: Carriers of the LRRK2 p.N551K-p.R1398H-p.K1423K haplotype have a reduced risk for developing RBD, yet PD-causing mutations probably have minor or no role in RBD. Additional work is needed to confirm these results and to identify the mechanism associated with reduced risk for RBD.

  • Full sequencing and haplotype analysis of MAPT in Parkinson's disease and rapid eye movement sleep Behavior Disorder
    Movement Disorders, 2018
    Co-Authors: Jennifer Ruskey, Isabelle Arnulf, Birgit Högl, Yves Dauvilliers, Claire S Leblond, Sirui Zhou, Amirthagowri Ambalavanan, Jay Ross, Cynthia Bourassa, Dan Spiegelman
    Abstract:

    BACKGROUND: MAPT haplotypes are associated with PD, but their association with rapid eye movement sleep Behavior Disorder is unclear. OBJECTIVE: To study the role of MAPT variants in rapid eye movement sleep Behavior Disorder. METHODS: Two cohorts were included: (A) PD (n = 600), rapid eye movement sleep Behavior Disorder (n = 613) patients, and controls (n = 981); (B) dementia with Lewy bodies patients with rapid eye movement sleep Behavior Disorder (n = 271) and controls (n = 950). MAPT-associated variants and the entire coding sequence of MAPT were analyzed. Age-, sex-, and ethnicity-adjusted analyses were performed to examine the association between MAPT, PD, and rapid eye movement sleep Behavior Disorder. RESULTS: MAPT-H2 variants were associated with PD (odds ratios: 0.62-0.65; P = 0.010-0.019), but not with rapid eye movement sleep Behavior Disorder. In PD, the H1 haplotype odds ratio was 1.60 (95% confidence interval: 1.12-2.28; P = 0.009), and the H2 odds ratio was 0.68 (95% confidence interval: 0.48-0.96; P = 0.03). The H2/H1 haplotypes were not associated with rapid eye movement sleep Behavior Disorder. CONCLUSIONS: Our results confirm the protective effect of the MAPT-H2 haplotype in PD, and define its components. Furthermore, our results suggest that MAPT does not play a major role in rapid eye movement sleep Behavior Disorder, emphasizing different genetic background than in PD in this locus. © 2018 International Parkinson and Movement Disorder Society.

  • The dementia-associated APOE ε4 allele is not associated with rapid eye movement sleep Behavior Disorder
    Neurobiology of Aging, 2017
    Co-Authors: Gan-or Ziv, Isabelle Arnulf, Jacques Montplaisir, Birgit Högl, Yves Dauvilliers, Ambra Stefani, Judes Poirier, Simon Warby, Stephanie Strong, Christelle Charley Monaca
    Abstract:

    The present study aimed to examine whether the APOE ε4 allele, associated with dementia with Lewy bodies (DLB), and possibly with dementia in Parkinson's disease (PD), is also associated with idiopathic rapid eye movement sleep Behavior Disorder (RBD). Two single nucleotide polymorphisms, rs429358 and rs7412, were genotyped in RBD patients (n = 480) and in controls (n = 823). APOE ε4 allele frequency was 0.14 among RBD patients and 0.13 among controls (OR = 1.11, 95% CI: 0.88-1.40, p = 0.41). APOE ε4 allele frequencies were similar in those who converted to DLB (0.14) and those who converted to Parkinson's disease (0.12) or multiple system atrophy (0.14, p = 1.0). The APOE ε4 allele is neither a risk factor for RBD nor it is associated with conversion from RBD to DLB or other synucleinopathies.

  • Loss of REM sleep features across nighttime in REM sleep Behavior Disorder
    Sleep Medicine, 2016
    Co-Authors: Dario Arnaldi, Marie Vidailhet, Alice Latimier, Smaranda Leu-semenescu, Isabelle Arnulf
    Abstract:

    Objectives Melatonin is a chronobiotic treatment which also alleviates rapid eye movement (REM) sleep Behavior Disorder (RBD). Because the mechanisms of this benefit are unclear, we evaluated the clock-dependent REM sleep characteristics in patients with RBD, whether idiopathic (iRBD) or associated with Parkinson's Disease (PD), and we compared findings with PD patients without RBD and with healthy subjects. Methods An overnight videopolysomnography was performed in ten iRBD patients, ten PD patients with RBD (PD + RBD+), ten PD patients without RBD (PD + RBD−), and ten controls. The rapid eye movement frequency per minute (REMs index), the tonic and phasic electromyographic (EMG) activity of the levator menti muscle, and the duration of each REM sleep episode were evaluated. A generalized linear model was applied in each group, with the REM sleep cycle (four ordinal levels) as the dependent variable, as a function of REMs index, REM sleep duration, and tonic and phasic EMG activity. Results From the first to the fourth sleep cycle, REM sleep duration progressively increased in controls only, REMs index increased in subjects without RBD but not in patients with RBD, whether idiopathic or associated with PD, whereas tonic and phasic EMG activity did not change. Conclusions Patients with PD or iRBD lost the physiologic nocturnal increase in REM sleep duration, and patients with RBD (either with or without PD) lost the increase of REMs frequency across the night, suggesting an alteration in the circadian system in RBD. This supports the hypothesis of a direct effect of melatonin on RBD symptoms by its chronobiotic activity.

A Iranzo - One of the best experts on this subject based on the ideXlab platform.

  • Significance of hyposmia in isolated REM sleep Behavior Disorder
    Journal of Neurology, 2020
    Co-Authors: A Iranzo, Paula Marrero-gonzález, Mónica Serradell, Carles Gaig, Joan Santamaria, Isabel Vilaseca
    Abstract:

    Objective To determine if hyposmia in isolated REM sleep Behavior Disorder (IRBD) predicts short-term conversion to any α-synucleinopathy and declines with time. Methods Olfaction was tested using the University of Pennsylvania Smell Identification Test (UPSIT-40) in 140 consecutive patients with polysomnography-confirmed IRBD and in 77 matched controls. Patients were followed-up during 5.6 ± 3.9 (range 0.2–13) years. Twenty-one patients underwent serial UPSIT-40 evaluations at 1–3 and 4–6 years after baseline. Results UPSIT-40 score was lower in patients than in controls (20.2 ± 6.5 vs. 28.6 ± 5.0; p  

  • The REM sleep circuit and how its impairment leads to REM sleep Behavior Disorder
    Cell and Tissue Research, 2018
    Co-Authors: A Iranzo
    Abstract:

    REM sleep is characterized by rapid eye movements, desynchronized electroencephalographic activity, dreams and muscle paralysis that preclude the individual from acting out the action of dreams. REM sleep is generated and modulated by a complex and still poorly understood, neuronal network that involves multiple nuclei and neurotransmission systems. The key structures that generate REM sleep muscle paralysis are the subcoeruleus nucleus in the mesopontine tegmentum and the reticular formation of the ventral medial medulla. Using glutamatergic, GABAergic and glycinergic inputs, direct and indirect projections from these two areas inhibit the motoneurons of the spinal cord resulting in skeletal paralysis in REM sleep. Experimental studies in cats and rodents where the subcoeruleus nucleus and ventral medial medulla were impaired by electrolytic, pharmacological and genetic manipulations have repeatedly produced increased electromyography activity during REM sleep associated with abnormal motor Behaviors (e.g., prominent twitching, attack-like Behaviors). These animal models represent the pathophysiological substrate of REM sleep Behavior Disorder, a parasomnia in humans characterized by nightmares and abnormal vigorous Behaviors (e.g., prominent jerking, shouting, kicking) linked to excessive phasic and/or tonic electromyographic activity in REM sleep. The extraordinary observation that a sleep Disorder is often the first manifestation of a devastating neurodegenerative disease such as Parkinson disease carries important diagnostic implications and opens a window for neuroprotection. This review addresses the neuronal substrates of REM sleep generation and modulation and how its impairment may lead to REM sleep Behavior Disorder.

  • longitudinal changes in cognition in early parkinson s disease patients with rem sleep Behavior Disorder
    Parkinsonism & Related Disorders, 2016
    Co-Authors: Lama M Chahine, Ronald B. Postuma, W H Oertel, A Iranzo, Sharon X Xie, Tanya Simuni, Baochan Tran, Amy W Amara, Christi Scordia, Michelle E Fullard
    Abstract:

    Abstract Introduction Cognitive decline is common in Parkinson's disease (PD), and identifying patients at highest risk for it is essential. We aimed to examine the effect of possible REM sleep Behavior Disorder (pRBD) on rate of cognitive decline in early PD, for both global cognition and in specific cognitive domains. Methods Parkinson's Progression Markers Initiative (PPMI) is a multi-site, international study of PD patients untreated at enrollment. pRBD was assessed with the REM sleep Behavior Disorder questionnaire (RBDSQ). Global cognition was assessed at baseline and annually using the Montreal Cognitive Assessment (MoCA) and a cognitive battery. Linear mixed effects models were used to examine the relationship between pRBD (RBDSQ ≥ 6) and rate of change in cognitive variables. Age, sex, years of education, and baseline motor and cognitive scores were included as covariates. Results The baseline sample consisted of 423 individuals with PD, mean age 61.7 years and 65.5% male. Data was available on 389, 366, and 196 participants at 1-year, 2-year, and 3-year follow-up respectively. Possible RBD occurred in 108 (25.5%) at baseline. In multivariate analyses, baseline RBD was associated with greater annual rate of decline in MoCA score (β = −0.34, 95%CI −0.54, −0.13, p  Conclusions Possible RBD is common in early PD and predicts future cognitive decline, particularly in attention and memory domains.

  • Risk factors for neurodegeneration in idiopathic rapid eye movement sleep Behavior Disorder: A multicenter study
    Annals of Neurology, 2015
    Co-Authors: Ronald B. Postuma, Isabelle Arnulf, Birgit Högl, Yves Dauvilliers, A Iranzo, Raffaele Manni, Tomoyuki Miyamoto, Luigi Ferini-strambi, Wolfgang Oertel, Monica Puligheddu
    Abstract:

    OBJECTIVE: To assess whether risk factors for Parkinson disease and dementia with Lewy bodies increase rate of defined neurodegenerative disease in idiopathic rapid eye movement (REM) sleep Behavior Disorder (RBD). METHODS: Twelve centers administered a detailed questionnaire assessing risk factors for neurodegenerative synucleinopathy to patients with idiopathic RBD. Variables included demographics, lifestyle factors, pesticide exposures, occupation, comorbid conditions, medication use, family history, and autonomic/motor symptoms. After 4 years of follow-up, patients were assessed for dementia or parkinsonism. Disease risk was assessed with Kaplan-Meier analysis, and epidemiologic variables were compared between convertors and those still idiopathic using logistic regression. RESULTS: Of 305 patients, follow-up information was available for 279, of whom 93 (33.3%) developed defined neurodegenerative disease. Disease risk was 25% at 3 years and 41% after 5 years. Patients who converted were older (difference = 4.5 years, p 

  • neurodegenerative Disorder risk in idiopathic rem sleep Behavior Disorder study in 174 patients
    PLOS ONE, 2014
    Co-Authors: A Iranzo, Mónica Serradell, Isabel Vilaseca, Francesc Valldeoriola, E Tolosa, Ana Fernandezarcos, Jose Luis Molinuevo, Ellen Gelpi, Raquel Sanchezvalle, Albert Llado
    Abstract:

    Objective To estimate the risk for developing a defined neurodegenerative syndrome in a large cohort of idiopathic REM sleep Behavior Disorder (IRBD) patients with long follow-up. Methods Using the Kaplan-Meier method, we estimated the disease-free survival rate from defined neurodegenerative syndromes in all the consecutive IRBD patients diagnosed and followed-up in our tertiary referal sleep center between November 1991 and July 2013. Results The cohort comprises 174 patients with a median age at diagnosis of IRBD of 69 years and a median follow-up of four years. The risk of a defined neurodegenerative syndrome from the time of IRBD diagnosis was 33.1% at five years, 75.7% at ten years, and 90.9% at 14 years. The median conversion time was 7.5 years. Emerging diagnoses (37.4%) were dementia with Lewy bodies (DLB) in 29 subjects, Parkinson disease (PD) in 22, multiple system atrophy (MSA) in two, and mild cognitive impairment (MCI) in 12. In six cases, in whom postmortem was performed, neuropathological examination disclosed neuronal loss and widespread Lewy-type pathology in the brain in each case. Conclusions In a large IRBD cohort diagnosed in a tertiary referal sleep center, prolonged follow-up indicated that the majority of patients are eventually diagnosed with the synucleinopathies PD, DLB and less frequently MSA. IRBD represented the prodromal period of these conditions. Our findings in IRBD have important implications in clinical practice, in the investigation of the early pathological events occurring in the synucleinopathies, and for the design of interventions with potential disease-modifying agents.