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3. Preliminary data on the Prodromal Synucleinopathy Rating Scale among patients with REM sleep behavior disorder

Author

Boeve, B., primary, Bui, Q., additional, De La Cruz, H., additional, Avidan, A., additional, Bliwise, D., additional, Campbell, M., additional, Criswell, S., additional, Davis, A., additional, Elliott, J., additional, Ehgoetz-Martens, K., additional, Ferman, T., additional, Fields, J., additional, Forsberg, L., additional, Gagnon, J.-F., additional, Gan-Or, Z., additional, Howell, M., additional, Hu, M., additional, Huddleston, D., additional, Kantarci, K., additional, Kotzbauer, P., additional, McLeland, J., additional, Lim, M., additional, Lowe, V., additional, Miglis, M., additional, Mignot, E., additional, Miyagawa, T., additional, Pelletier, A., additional, Ross, O., additional, Singer, W., additional, St. Louis, E., additional, Videnovic, A., additional, Xiong, C., additional, Postuma, R., additional, and Ju, Y.-E., additional

Published
2024
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4. Rapid eye movement sleep behavior disorder: devising controlled active treatment studies for symptomatic and neuroprotective therapy—a consensus statement from the International Rapid Eye Movement Sleep Behavior Disorder Study Group

Author

Schenck, CH, Montplaisir, JY, Frauscher, B, Hogl, B, Gagnon, J-F, Postuma, R, Sonka, K, Jennum, P, Partinen, M, Arnulf, I, de Cock, V Cochen, Dauvilliers, Y, Luppi, P-H, Heidbreder, A, Mayer, G, Sixel-Döring, F, Trenkwalder, C, Unger, M, Young, P, Wing, YK, Ferini-Strambi, L, Ferri, R, Plazzi, G, Zucconi, M, Inoue, Y, Iranzo, A, Santamaria, J, Bassetti, C, Möller, JC, Boeve, BF, Lai, YY, Pavlova, M, Saper, C, Schmidt, P, Siegel, JM, Singer, C, St Louis, E, Videnovic, A, and Oertel, W

Subjects
Biomedical and Clinical Sciences, Clinical Sciences, Clinical Trials and Supportive Activities, Brain Disorders, Prevention, Aging, Acquired Cognitive Impairment, Neurosciences, Clinical Research, Neurodegenerative, Parkinson's Disease, Lewy Body Dementia, Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD), Sleep Research, Mental Health, Alzheimer's Disease Related Dementias (ADRD), Behavioral and Social Science, Dementia, Neurological, Clinical Trials as Topic, Clonazepam, Consensus, GABA Modulators, Humans, Melatonin, Neuroprotective Agents, Parkinson Disease, REM Sleep Behavior Disorder, Risk Factors, REM sleep behavior disorder, RBD, Treatment studies, Neuroprotective studies, Parkinson disease, PD, alpha-Synucleinopathies, Videopolysomnography, α-Synucleinopathies, Psychology, Neurology & Neurosurgery, Clinical sciences, Clinical and health psychology
Abstract

ObjectivesWe aimed to provide a consensus statement by the International Rapid Eye Movement Sleep Behavior Disorder Study Group (IRBD-SG) on devising controlled active treatment studies in rapid eye movement sleep behavior disorder (RBD) and devising studies of neuroprotection against Parkinson disease (PD) and related neurodegeneration in RBD.MethodsThe consensus statement was generated during the fourth IRBD-SG symposium in Marburg, Germany in 2011. The IRBD-SG identified essential methodologic components for a randomized trial in RBD, including potential screening and diagnostic criteria, inclusion and exclusion criteria, primary and secondary outcomes for symptomatic therapy trials (particularly for melatonin and clonazepam), and potential primary and secondary outcomes for eventual trials with disease-modifying and neuroprotective agents. The latter trials are considered urgent, given the high conversion rate from idiopathic RBD (iRBD) to Parkinsonian disorders (i.e., PD, dementia with Lewy bodies [DLB], multiple system atrophy [MSA]).ResultsSix inclusion criteria were identified for symptomatic therapy and neuroprotective trials: (1) diagnosis of RBD needs to satisfy the International Classification of Sleep Disorders, second edition, (ICSD-2) criteria; (2) minimum frequency of RBD episodes should preferably be ⩾2 times weekly to allow for assessment of change; (3) if the PD-RBD target population is included, it should be in the early stages of PD defined as Hoehn and Yahr stages 1-3 in Off (untreated); (4) iRBD patients with soft neurologic dysfunction and with operational criteria established by the consensus of study investigators; (5) patients with mild cognitive impairment (MCI); and (6) optimally treated comorbid OSA. Twenty-four exclusion criteria were identified. The primary outcome measure for RBD treatment trials was determined to be the Clinical Global Impression (CGI) efficacy index, consisting of a four-point scale with a four-point side-effect scale. Assessment of video-polysomnographic (vPSG) changes holds promise but is costly and needs further elaboration. Secondary outcome measures include sleep diaries; sleepiness scales; PD sleep scale 2 (PDSS-2); serial motor examinations; cognitive indices; mood and anxiety indices; assessment of frequency of falls, gait impairment, and apathy; fatigue severity scale; and actigraphy and customized bed alarm systems. Consensus also was established for evaluating the clinical and vPSG aspects of RBD. End points for neuroprotective trials in RBD, taking lessons from research in PD, should be focused on the ultimate goal of determining the performance of disease-modifying agents. To date no compound with convincing evidence of disease-modifying or neuroprotective efficacy has been identified in PD. Nevertheless, iRBD patients are considered ideal candidates for neuroprotective studies.ConclusionsThe IRBD-SG provides an important platform for developing multinational collaborative studies on RBD such as on environmental risk factors for iRBD, as recently reported in a peer-reviewed journal article, and on controlled active treatment studies for symptomatic and neuroprotective therapy that emerged during the 2011 consensus conference in Marburg, Germany, as described in our report.

Published
2013

5. Brain atrophy in REM sleep behavior disorder is shaped by gene expression and structural connectivity

Author

Rahayel, S., primary, Tremblay, C., additional, Vo, A., additional, Lehéricy, S., additional, Arnulf, I., additional, Vidailhet, M., additional, Corvol, J.-C., additional, Study Group, I., additional, Gagnon, J.-F., additional, Postuma, R., additional, Montplaisir, J., additional, Lewis, S., additional, Matar, E., additional, Ehgoetz Martens, K., additional, Borghammer, P., additional, Knudsen, K., additional, Monchi, O., additional, Misic, B., additional, and Dagher, A., additional

Published
2022
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9. Genome-wide association study of REM sleep behavior disorder identifies polygenic risk and brain expression effects

Author

Krohn, L., Heilbron, K., Blauwendraat, C., Reynolds, R. H., Yu, E., Senkevich, K., Rudakou, U., Estiar, M. A., Gustavsson, E. K., Brolin, K., Ruskey, J. A., Freeman, K., Asayesh, F., Chia, R., Arnulf, I., M. T. M., Hu, Montplaisir, J. Y., Gagnon, J. -F., Desautels, A., Dauvilliers, Y., Gigli, G. L., Valente, M., Janes, F., Bernardini, A., Hogl, B., Stefani, A., Ibrahim, A., Sonka, K., Kemlink, D., Oertel, W., Janzen, A., Plazzi, G., Biscarini, F., Antelmi, E., Figorilli, M., Puligheddu, M., Mollenhauer, B., Trenkwalder, C., Sixel-Doring, F., Cochen De Cock, V., Monaca, C. C., Heidbreder, A., Ferini-Strambi, L., Dijkstra, F., Viaene, M., Abril, B., Boeve, B. F., Aslibekyan, S., Auton, A., Babalola, E., Bell, R. K., Bielenberg, J., Bryc, K., Bullis, E., Coker, D., Partida, G. C., Dhamija, D., Das, S., Elson, S. L., Filshtein, T., Fletez-Brant, K., Fontanillas, P., Freyman, W., Gandhi, P. M., Hicks, B., Hinds, D. A., Jewett, E. M., Jiang, Y., Kukar, K., Lin, K. -H., Lowe, M., Mccreight, J. C., Mcintyre, M. H., Micheletti, S. J., Moreno, M. E., Mountain, J. L., Nandakumar, P., Noblin, E. S., O'Connell, J., Petrakovitz, A. A., Poznik, G. D., Schumacher, M., Shastri, A. J., Shelton, J. F., Shi, J., Shringarpure, S., Tran, V., Tung, J. Y., Wang, X., Wang, W., Weldon, C. H., Wilton, P., Hernandez, A., Wong, C., Tchakoute, C. T., Scholz, S. W., Ryten, M., Bandres-Ciga, S., Noyce, A., Cannon, P., Pihlstrom, L., Nalls, M. A., Singleton, A. B., Rouleau, G. A., Postuma, R. B., Gan-Or, Z., and 23andMe Research Team

Subjects
Multidisciplinary, Risk factors, General Physics and Astronomy, Genomics, General Chemistry, Human medicine, Genome-wide association studies, General Biochemistry, Genetics and Molecular Biology
Abstract

Rapid-eye movement (REM) sleep behavior disorder (RBD), enactment of dreams during REM sleep, is an early clinical symptom of alpha-synucleinopathies and defines a more severe subtype. The genetic background of RBD and its underlying mechanisms are not well understood. Here, we perform a genome-wide association study of RBD, identifying five RBD risk loci near SNCA, GBA, TMEM175, INPP5F, and SCARB2. Expression analyses highlight SNCA-AS1 and potentially SCARB2 differential expression in different brain regions in RBD, with SNCA-AS1 further supported by colocalization analyses. Polygenic risk score, pathway analysis, and genetic correlations provide further insights into RBD genetics, highlighting RBD as a unique alpha-synucleinopathy subpopulation that will allow future early intervention. REM-sleep behavior disorder often precedes Parkinson's disease or dementia. Here, the authors perform a genome-wide association study for REM-sleep behavior disorder, and discover how it potentially affects gene expression in the brain.

Published
2022

11. Safety and efficacy of tilavonemab in progressive supranuclear palsy: a phase 2, randomised, placebo-controlled trial

Author

Hoglinger, G. U., Litvan, I., Mendonca, N., Wang, D., Zheng, H., Rendenbach-Mueller, B., Lon, H. -K., Jin, Z., Fisseha, N., Budur, K., Gold, M., Ryman, D., Florian, H., Ahmed, A., Aiba, I., Albanese, Alberto, Bertram, K., Bordelon, Y., Bower, J., Brosch, J., Claassen, D., Colosimo, C., Corvol, J. -C., Cudia, P., Daniele, Antonio, Defebvre, L., Driver-Dunckley, E., Duquette, A., Eleopra, R., Eusebio, A., Fung, V., Geldmacher, D., Golbe, L., Grandas, F., Hall, D., Hatano, T., Honig, L., Hui, J., Kerwin, D., Kikuchi, A., Kimber, T., Kimura, T., Kumar, R., Ljubenkov, P., Lorenzl, S., Ludolph, A., Mari, Z., Mcfarland, N., Meissner, W., Mir Rivera, P., Mochizuki, H., Morgan, J., Munhoz, R., Nishikawa, N., O`sullivan, J., Oeda, T., Oizumi, H., Onodera, O., Ory-Magne, F., Peckham, E., Postuma, R., Quattrone, A., Quinn, J., Ruggieri, S., Sarna, J., Schulz, P. E., Slevin, J., Tagliati, M., Wile, D., Wszolek, Z., Xie, T., Zesiewicz, T., Albanese A. (ORCID:0000-0002-5864-0006), Hoglinger, G. U., Litvan, I., Mendonca, N., Wang, D., Zheng, H., Rendenbach-Mueller, B., Lon, H. -K., Jin, Z., Fisseha, N., Budur, K., Gold, M., Ryman, D., Florian, H., Ahmed, A., Aiba, I., Albanese, Alberto, Bertram, K., Bordelon, Y., Bower, J., Brosch, J., Claassen, D., Colosimo, C., Corvol, J. -C., Cudia, P., Daniele, Antonio, Defebvre, L., Driver-Dunckley, E., Duquette, A., Eleopra, R., Eusebio, A., Fung, V., Geldmacher, D., Golbe, L., Grandas, F., Hall, D., Hatano, T., Honig, L., Hui, J., Kerwin, D., Kikuchi, A., Kimber, T., Kimura, T., Kumar, R., Ljubenkov, P., Lorenzl, S., Ludolph, A., Mari, Z., Mcfarland, N., Meissner, W., Mir Rivera, P., Mochizuki, H., Morgan, J., Munhoz, R., Nishikawa, N., O`sullivan, J., Oeda, T., Oizumi, H., Onodera, O., Ory-Magne, F., Peckham, E., Postuma, R., Quattrone, A., Quinn, J., Ruggieri, S., Sarna, J., Schulz, P. E., Slevin, J., Tagliati, M., Wile, D., Wszolek, Z., Xie, T., Zesiewicz, T., and Albanese A. (ORCID:0000-0002-5864-0006)

Abstract

Background: Progressive supranuclear palsy is a neurodegenerative disorder associated with tau protein aggregation. Tilavonemab (ABBV-8E12) is a monoclonal antibody that binds to the N-terminus of human tau. We assessed the safety and efficacy of tilavonemab for the treatment of progressive supranuclear palsy. Methods: We did a phase 2, multicentre, randomised, placebo-controlled, double-blind study at 66 hospitals and clinics in Australia, Canada, France, Germany, Italy, Japan, Spain, and the USA. Participants (aged ≥40 years) diagnosed with possible or probable progressive supranuclear palsy who were symptomatic for less than 5 years, had a reliable study partner, and were able to walk five steps with minimal assistance, were randomly assigned (1:1:1) by interactive response technology to tilavonemab 2000 mg, tilavonemab 4000 mg, or matching placebo administered intravenously on days 1, 15, and 29, then every 28 days through to the end of the 52-week treatment period. Randomisation was done by the randomisation specialist of the study sponsor, who did not otherwise participate in the study. The sponsor, investigators, and participants were unaware of treatment allocations. The primary endpoint was the change from baseline to week 52 in the Progressive Supranuclear Palsy Rating Scale (PSPRS) total score in the intention-to-treat population. Adverse events were monitored in participants who received at least one dose of study drug. Prespecified interim futility criteria were based on a model-based effect size of 0 or lower when 60 participants had completed the 52-week treatment period and 0·12 or lower when 120 participants had completed the 52-week treatment period. This study is registered at ClinicalTrials.gov, number NCT02985879. Findings: Between Dec 12, 2016, and Dec 31, 2018, 466 participants were screened, 378 were randomised. The study was terminated on July 3, 2019, after prespecified futility criteria were met at the second interim analysis. A total of 3

Published
2021

17. Beneficial effect of 24-month bilateral subthalamic stimulation on quality of sleep in Parkinson's disease

Author

Dafsari, H. S., Ray-Chaudhuri, K., Ashkan, K., Sachse, L., Mahlstedt, P., Silverdale, M., Rizos, A., Strack, M., Jost, S. T., Reker, P., Samuel, M., Visser-Vandewalle, V., Evans, J., Antonini, A., Martinez-Martin, P., Timmermann, L., Schrag, A., Weintraub, D., Barone, P., Brooks, D. J., Brown, R. G., Jenner, P., Jeon, B., Lyons, K., Pavese, N., Politis, M., Postuma, R. B., Schapira, A., Stocchi, F., Tsuboi, Y., Sauerbier, A., Deutsche Forschungsgemeinschaft (Alemania), NIHR - Mental Health Biomedical Research Centre (Reino Unido), Dementia Unit at South London, South London and Maudsley NHS Foundation Trust (Reino Unido), King College London, German Research Foundation, National Institute of Health Research (NIHR) Mental Health Biomedical Research Centre, and Maudsley NHS Foundation Trust and King’s College London

Subjects
0301 basic medicine, Male, Sleep Wake Disorders, Quality of life, medicine.medical_specialty, Deep brain stimulation, Parkinson's disease, Neurology, Activities of daily living, medicine.medical_treatment, Deep Brain Stimulation, Non-motor symptoms, Subthalamic nucleus, 03 medical and health sciences, 0302 clinical medicine, Physical medicine and rehabilitation, Parkinson’s disease sleep scale, Outcome Assessment, Health Care, medicine, Humans, Prospective Studies, Aged, Original Communication, business.industry, Parkinson Disease, Middle Aged, medicine.disease, nervous system diseases, 030104 developmental biology, surgical procedures, operative, Observational study, Female, Neurology (clinical), Analysis of variance, business, 030217 neurology & neurosurgery, Follow-Up Studies
Abstract

Background Subthalamic nucleus (STN) deep brain stimulation (DBS) improves quality of life (QoL), motor, and sleep symptoms in Parkinson’s disease (PD). However, the long-term effects of STN-DBS on sleep and its relationship with QoL outcome are unclear. Methods In this prospective, observational, multicenter study including 73 PD patients undergoing bilateral STN-DBS, we examined PDSleep Scale (PDSS), PDQuestionnaire-8 (PDQ-8), Scales for Outcomes in PD-motor examination, -activities of daily living, and -complications (SCOPA-A, -B, -C), and levodopa-equivalent daily dose (LEDD) preoperatively, at 5 and 24 months follow-up. Longitudinal changes were analyzed with Friedman-tests or repeated-measures ANOVA, when parametric tests were applicable, and Bonferroni-correction for multiple comparisons. Post-hoc, visits were compared with Wilcoxon signed-rank/t-tests. The magnitude of clinical responses was investigated using effect size. Results Significant beneficial effects of STN-DBS were observed for PDSS, PDQ-8, SCOPA-A, -B, and -C. All outcomes improved significantly at 5 months with subsequent decrements in gains at 24 months follow-up which were significant for PDSS, PDQ-8, and SCOPA-B. Comparing baseline and 24 months follow-up, we observed significant improvements of PDSS (small effect), SCOPA-A (moderate effect), -C, and LEDD (large effects). PDSS and PDQ-8 improvements correlated significantly at 5 and 24 months follow-up. Conclusions In this multicenter study with a 24 months follow-up, we report significant sustained improvements after bilateral STN-DBS using a PD-specific sleep scale and a significant relationship between sleep and QoL improvements. This highlights the importance of sleep in holistic assessments of DBS outcomes.

Published
2020
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18. A brain signature of prodromal Lewy body dementia in isolated REM sleep behavior disorder

Author

Rahayel, S., Postuma, R., Montplaisir, J., Misic, B., Tremblay, C., Vo, A., Lewis, S., Matar, E., Martens, K. Ehgoetz, Blanc, F., Yao, C., Pelletier, Amandine, Gaubert, M., Carrier, J., Monchi, O., Chouinard, S., Panisset, M., Dagher, A., Gagnon, J. -F., Université Laval [Québec] (ULaval), The Open University [Milton Keynes] (OU), Institut des Sciences Moléculaires d'Orsay (ISMO), Université Paris-Sud - Paris 11 (UP11)-Centre National de la Recherche Scientifique (CNRS), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Université de Montpellier (UM), Périnatalité et Risques Toxiques - UMR INERIS_I 1 (PERITOX), Institut National de l'Environnement Industriel et des Risques (INERIS)-Université de Picardie Jules Verne (UPJV)-CHU Amiens-Picardie, Service de cardiologie [Hôpital Nord - APHM], Aix Marseille Université (AMU)-Assistance Publique - Hôpitaux de Marseille (APHM)- Hôpital Nord [CHU - APHM], IFP Energies nouvelles (IFPEN), Université de Pau et des Pays de l'Adour (UPPA), Montreal Neurological Institute and Hospital, and McGill University = Université McGill [Montréal, Canada]

Subjects
Cognitive dysfunction, Dementia with Lewy bodies (DLB), [SDV]Life Sciences [q-bio], Magnetic resonance imaging(MRI)
Abstract

25th Congress of the European-Sleep-Research-Society (ESRS), ELECTR NETWORK, SEP 22-24, 2020; International audience

Published
2020

24. Full sequencing and haplotype analysis of MAPT in Parkinson's disease and rapid eye movement sleep behavior disorder

Author

Li, J, Ruskey, J, Arnulf, I, Dauvilliers, Y, Hu, M, Högl, B, Leblond, C, Zhou, S, Ambalavanan, A, Ross, J, Bourassa, C, Spiegelman, D, Laurent, S, Stefani, A, Charley Monaca, C, Cochen De Cock, V, Boivin, M, Ferini-Strambi, L, Plazzi, G, Antelmi, E, Young, P, Heidbreder, A, Labbe, C, Ferman, T, Dion, P, Fan, D, Desautels, A, Gagnon, J, Dupré, N, Fon, E, Montplaisir, J, Boeve, B, Postuma, R, Rouleau, G, Ross, O, Gan-Or, Z, Li, J., Ruskey, J. A., Arnulf, I., Dauvilliers, Y., M. T. M., Hu, Hogl, B., Leblond, C. S., Zhou, S., Ambalavanan, A., Ross, J. P., Bourassa, C. V., Spiegelman, D., Laurent, S. B., Stefani, A., Charley Monaca, C., Cochen De Cock, V., Boivin, M., Ferini-Strambi, L., Plazzi, G., Antelmi, E., Young, P., Heidbreder, A., Labbe, C., Ferman, T. J., Dion, P. A., Fan, D., Desautels, A., Gagnon, J. -F., Dupre, N., Fon, E. A., Montplaisir, J. Y., Boeve, B. F., Postuma, R. B., Rouleau, G. A., Ross, O. A., Gan-Or, Z., Service des Pathologies du sommeil [CHU Pitié-Salpêtrière], CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Institut du Cerveau et de la Moëlle Epinière = Brain and Spine Institute (ICM), Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Département de neurologie [Montpellier], Université Montpellier 1 (UM1)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Hôpital Gui de Chauliac [Montpellier]-Université de Montpellier (UM), Neuropsychiatrie : recherche épidémiologique et clinique (PSNREC), Université Montpellier 1 (UM1)-Université de Montpellier (UM)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de neurophysiologie clinique (CHRU Lille), Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Euromov (EuroMov), Université de Montpellier (UM), Clinique Beau Soleil [Montpellier], Li, Jiao, Ruskey, Jennifer A., Arnulf, Isabelle, Dauvilliers, Yve, Hu, Michele T.M., Högl, Birgit, Leblond, Claire S., Zhou, Sirui, Ambalavanan, Amirthagowri, Ross, Jay P., Bourassa, Cynthia V., Spiegelman, Dan, Laurent, Sandra B, Stefani, Ambra, Charley Monaca, Christelle, Cochen De Cock, Valérie, Boivin, Michel, Ferini-Strambi, Luigi, Plazzi, Giuseppe, Antelmi, Elena, Young, Peter, Heidbreder, Anna, Labbe, Catherine, Ferman, Tanis J., Dion, Patrick A., Fan, Dongsheng, Desautels, Alex, Gagnon, Jean-Françoi, Dupré, Nicola, Fon, Edward A., Montplaisir, Jacques Y., Boeve, Bradley F., Postuma, Ronald B., Rouleau, Guy A., Ross, Owen A., and Gan-Or, Ziv

Subjects
Lewy Body Disease, Male, Principal Component Analysis, Genotype, Parkinson's disease, REM sleep behavior disorder, Parkinson Disease, tau Proteins, Middle Aged, Polymorphism, Single Nucleotide, Cohort Studies, Neurology, Gene Frequency, genetics, MAPT, Neurology (clinical), Humans, [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], Female, Genetic Predisposition to Disease, genetic, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, Aged
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.

Published
2018
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39. High burden of neurological disease in the older general population: results from the Canadian Longitudinal Study on Aging.

Author

Wolfson, C., Fereshtehnejad, S.‐M., Pasquet, R., Postuma, R., and Keezer, M. R.

Subjects
PARKINSON'S disease, NEUROLOGICAL disorders, MEDICAL care, DISEASE prevalence, NEUROLOGY
Abstract

Background and purpose: Our objective was to study the association between the presence of a neurological disease and the comorbidity burden as well as healthcare utilization (HCU). Methods: Using baseline data from the Canadian Longitudinal Study on Aging (CLSA), we examined the burden of five neurological conditions. The CLSA is a population‐based study of approximately 50 000 individuals, aged 45–85 years at baseline. We used multivariable Poisson regression to identify correlates of comorbidity burden and HCU. Results: The lifetime prevalence of five neurological diseases is presented: epilepsy, Parkinson's disease/parkinsonism, stroke/transient ischaemic attack, multiple sclerosis and migraine. We found the somatic and psychiatric comorbidity burden to be higher in those individuals with a neurological disease (an 18–45% mean increase in the number of chronic conditions) as compared with the comparison group without a neurological disease, except for Parkinson's disease/parkinsonism. The presence of a neurological disease was associated with only a modest increase in the probability of visiting a general practitioner but was associated with a greatly increased probability of visiting a medical specialist (up to 68% more likely) or an emergency department (up to 79% more likely) and an overnight hospitalization (up to 108% more likely). Conclusions: We found striking associations between our neurological diseases and increased comorbidity burdens and HCU. These findings are important for informing public policy planning as well as driving avenues for future research. The present study established the CLSA as an important research platform for the study of neurological conditions in an aging general population. [ABSTRACT FROM AUTHOR]

Published
2019
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40. The GBA p.Trp378Gly mutation is a probable French‐Canadian founder mutation causing Gaucher disease and synucleinopathies.

Author

Ruskey, J. A., Zhou, S., Santiago, R., Franche, L.‐A., Alam, A., Roncière, L., Spiegelman, D., Fon, E. A., Trempe, J.‐F., Kalia, L. V., Postuma, R. B., Dupre, N., Rivard, G.‐E., Assouline, S., Amato, D., and Gan‐Or, Z.

Subjects
GAUCHER'S disease, PARKINSON'S disease, RAPID eye movement sleep, HAPLOTYPES, SINGLE nucleotide polymorphisms
Abstract

Biallelic GBA mutations cause Gaucher disease (GD), and heterozygous carriers are at risk for synucleinopathies. No founder GBA mutations in French‐Canadians are known. GBA was fully sequenced using targeted next generation and Sanger sequencing in French‐Canadian Parkinson disease (PD) patients (n = 436), rapid eye movement (REM)‐sleep behavior disorder (RBD) patients (n = 189) and controls (n = 891). Haplotype, identity‐by‐descent (IBD) and principal component analyses (PCA) were performed using single nucleotide polymorphism‐chip data. Data on GD patients from Toronto and Montreal were collected from patients' files. A GBA p.Trp378Gly mutation was identified in two RBD and four PD patients (1% of all patients combined), and not in controls. The two RBD patients had converted to DLB within 3 years of their diagnosis. Haplotype, IBD and PCA analysis demonstrated that this mutation is from a single founder. Out of 167 GD patients screened, 15 (9.0%) carried the p.Trp378Gly mutation, all in trans with p.Asn370Ser. Three (20%) of the GD patients with the p.Trp378Gly mutation had developed Parkinsonism, and 11 patients had family history of PD. The p.Trp378Gly mutation is the first French‐Canadian founder GBA mutation to be described, which leads to synucleinopathies and to GD type 1 when in compound heterozygosity with p.Asn370Ser. [ABSTRACT FROM AUTHOR]

Published
2018
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44. Comorbidity and medication in REM sleep behavior disorder: A multicenter case-control study

Author

Frauscher, B., primary, Jennum, P., additional, Ju, Y.-E. S., additional, Postuma, R. B., additional, Arnulf, I., additional, Cochen De Cock, V., additional, Dauvilliers, Y., additional, Fantini, M. L., additional, Ferini-Strambi, L., additional, Gabelia, D., additional, Iranzo, A., additional, Leu-Semenescu, S., additional, Mitterling, T., additional, Miyamoto, M., additional, Miyamoto, T., additional, Montplaisir, J. Y., additional, Oertel, W., additional, Pelletier, A., additional, Prunetti, P., additional, Puligheddu, M., additional, Santamaria, J., additional, Sonka, K., additional, Unger, M., additional, Wolfson, C., additional, Zucconi, M., additional, Terzaghi, M., additional, Hogl, B., additional, Mayer, G., additional, and Manni, R., additional

Published
2014
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46. Corrigendum to “Rapid eye movement sleep behavior disorder: devising controlled active treatment studies for symptomatic and neuroprotective therapy—a consensus statement from the International Rapid Eye Movement Sleep Behavior Disorder Study Group” [Sleep Med 14(8) (2013) 795–806]

Author

Schenck, C.H., primary, Montplaisir, J.Y., additional, Frauscher, B., additional, Hogl, B., additional, Gagnon, J.-F., additional, Postuma, R., additional, Sonka, K., additional, Jennum, P., additional, Partinen, M., additional, Arnulf, I., additional, de Cock, V. Cochen, additional, Dauvilliers, Y., additional, Luppi, P.-H., additional, Heidbreder, A., additional, Mayer, G., additional, Sixel-Döring, F., additional, Trenkwalder, C., additional, Unger, M., additional, Young, P., additional, Wing, Y.K., additional, Ferini-Strambi, L., additional, Ferri, R., additional, Plazzi, G., additional, Zucconi, M., additional, Inoue, Y., additional, Iranzo, A., additional, Santamaria, J., additional, Bassetti, C., additional, Möller, J.C., additional, Boeve, B.F., additional, Lai, Y.Y., additional, Pavlova, M., additional, Saper, C., additional, Schmidt, P., additional, Siegel, J.M., additional, Singer, C., additional, St Louis, E., additional, Videnovic, A., additional, and Oertel, W., additional

Published
2014
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47. Rapid eye movement sleep behavior disorder:devising controlled active treatment studies for symptomatic and neuroprotective therapy—a consensus statement from the International Rapid Eye Movement Sleep Behavior Disorder Study Group

Author

Schenck, C H, Montplaisir, J Y, Frauscher, B, Hogl, B, Gagnon, J-F, Postuma, R, Sonka, K, Jennum, P, Partinen, M, Arnulf, I, Cochen de Cock, V, Dauvilliers, Y, Luppi, P-H, Heidbreder, A, Mayer, G, Sixel-Döring, F, Trenkwalder, C, Unger, M, Young, P, Wing, Y K, Ferini-Strambi, L, Ferri, R, Plazzi, G, Zucconi, M, Inoue, Y, Iranzo, A, Santamaria, J, Bassetti, C, Möller, J C, Boeve, B F, Lai, Yoke-Chin, Pavlova, M, Saper, C, Schmidt, P, Siegel, J M, Singer, C, St Louis, E, Videnovic, A, Oertel, W, Schenck, C H, Montplaisir, J Y, Frauscher, B, Hogl, B, Gagnon, J-F, Postuma, R, Sonka, K, Jennum, P, Partinen, M, Arnulf, I, Cochen de Cock, V, Dauvilliers, Y, Luppi, P-H, Heidbreder, A, Mayer, G, Sixel-Döring, F, Trenkwalder, C, Unger, M, Young, P, Wing, Y K, Ferini-Strambi, L, Ferri, R, Plazzi, G, Zucconi, M, Inoue, Y, Iranzo, A, Santamaria, J, Bassetti, C, Möller, J C, Boeve, B F, Lai, Yoke-Chin, Pavlova, M, Saper, C, Schmidt, P, Siegel, J M, Singer, C, St Louis, E, Videnovic, A, and Oertel, W

Published
2013

48. De leerling voelt zich thuis bij de opleiding Helpende Zorg en Welzijn.

Author

Postuma, R., Sol, Y. B. (Thesis Advisor), Stokking, K.M., Postuma, R., Sol, Y. B. (Thesis Advisor), and Stokking, K.M.

Abstract

Jongeren die een opleiding bij het ROC op niveau 1 of 2 doen, hebben veel kans hebben om voortijdig schoolverlater te worden. Oorzaken hiervoor liggen zowel buiten de school als binnen de leeromgeving. Uit onderzoek blijkt dat het belangrijk is voor leerlingen dat ze zich “thuis voelen” bij de opleiding. Via een literatuur studie zijn factoren gegenereerd die voor de leerling belangrijk zijn om zich thuis te voelen bij de opleiding. De volgende factoren kwamen naar voren: relatie leerling docent, relatie peers en schoolklimaat. Met behulp van een vragenlijst is onderzocht wat de ervaringen en de wensen van leerlingen en docenten zijn met betrekking tot het zich thuis voelen bij de opleiding en deze onderliggende factoren.

Published
2012

49. Environmental risk factors for REM sleep behavior disorder:a multicenter case-control study

Author

Postuma, R B, Montplaisir, J Y, Pelletier, A, Dauvilliers, Y, Oertel, W, Iranzo, A, Ferini-Strambi, L, Arnulf, I, Hogl, B, Manni, R, Miyamoto, T, Mayer, G, Stiasny-Kolster, K, Puligheddu, M, Ju, Y, Jennum, P, Sonka, K, Santamaria, J, Fantini, M L, Zucconi, M, Leu-Semenescu, S, Frauscher, B, Terzaghi, M, Miyamoto, M, Unger, M M, Cochen De Cock, V, Wolfson, C, Postuma, R B, Montplaisir, J Y, Pelletier, A, Dauvilliers, Y, Oertel, W, Iranzo, A, Ferini-Strambi, L, Arnulf, I, Hogl, B, Manni, R, Miyamoto, T, Mayer, G, Stiasny-Kolster, K, Puligheddu, M, Ju, Y, Jennum, P, Sonka, K, Santamaria, J, Fantini, M L, Zucconi, M, Leu-Semenescu, S, Frauscher, B, Terzaghi, M, Miyamoto, M, Unger, M M, Cochen De Cock, V, and Wolfson, C

Abstract

Idiopathic REM sleep behavior disorder is a parasomnia characterized by dream enactment and is commonly a prediagnostic sign of parkinsonism and dementia. Since risk factors have not been defined, we initiated a multicenter case-control study to assess environmental and lifestyle risk factors for REM sleep behavior disorder.

Published
2012

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