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Behavior Disorder

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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, Jacques Montplaisir, Amélie Pelletier, Jessie De Roy, 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, Jacques Montplaisir, Isabelle Arnulf, Jennifer Ruskey, Armaghan Alam, Naomi C Futhey, Lynne Krohn, Karl Heilbron, Paul Cannon, 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, Jacques Montplaisir, Amélie Pelletier, 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

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, Jacques Montplaisir, Amélie Pelletier, Jessie De Roy, 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, Jacques Montplaisir, Amélie Pelletier, 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.

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, Jacques Montplaisir, Amélie Pelletier, Jessie De Roy, 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, Jacques Montplaisir, Isabelle Arnulf, Jennifer Ruskey, Armaghan Alam, Naomi C Futhey, Lynne Krohn, Karl Heilbron, Paul Cannon, 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, Jean-françois Gagnon, Isabelle Arnulf, 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.