Risk and predictors of dementia and parkinsonism in idiopathic REM sleep behaviour disorder: a multicentre study - Université de Montpellier
Article Dans Une Revue Brain - A Journal of Neurology Année : 2019

Risk and predictors of dementia and parkinsonism in idiopathic REM sleep behaviour disorder: a multicentre study

Ronald B. Postuma (1) , Alex Iranzo , Michele Hu , Birgit Högl (2) , Bradley Boeve (3) , Raffaele Manni , Wolfgang Oertel (4) , Isabelle Arnulf (5) , Luigi Ferini-Strambi (6) , Monica Puligheddu , Elena Antelmi (7) , Valérie Cochen de Cock (8) , Dario Arnaldi (9) , Brit Mollenhauer (10) , Aleksandar Videnovic , Karel Sonka (11) , Ki-Young Jung (12) , Dieter Kunz , Yves M Dauvilliers (13, 14) , Federica Provini , Simon Lewis , Jitka Buskova , Milena Pavlova , Anna Heidbreder (15) , Jacques Montplaisir (16) , Joan Santamaria (8) , Thomas Barber (17) , Ambra Stefani (2) , Erik St Louis , Michele Terzaghi , Annette Janzen , Smandra Leu-Semenescu (5) , Guiseppe Plazzi , Flavio Nobili (9) , Friederike Sixel-Doering , Petr Dusek , Frederik Bes , Pietro Cortelli (18) , Kaylena Ehgoetz Martens , Jean-François Gagnon (19) , Carles Gaig , Marco Zucconi (6) , Claudia Trenkwalder (9) , Ziv Gan-Or (1) , Christine Lo , Michal Rolinski (17) , Philip Mahlknecht , Evi Holzknecht , Angel Boeve , Luke Teigen , Gianpaolo Toscano , Geert Mayer , Silvia Morbelli (9) , Benjamin Dawson , Amélie Pelletier (16) , Erik St.Louis
1 McGill University = Université McGill [Montréal, Canada]
2 IMU - Innsbruck Medical University = Medizinische Universität Innsbruck
3 Mayo Clinic [Rochester]
4 Philipps Universität Marburg = Philipps University of Marburg
5 CHU Pitié-Salpêtrière [AP-HP]
6 UniSR - Universita Vita Salute San Raffaele = Vita-Salute San Raffaele University [Milan, Italie]
7 UNIBO - Alma Mater Studiorum Università di Bologna = University of Bologna
8 EuroMov - Euromov
9 UniGe - Università degli studi di Genova = University of Genoa
10 UMG - University Medical Center Göttingen
11 1. LF UK / 1st Faculty of Medicine - 1. lékařská fakulta, Univerzita Karlova [Praha, Česká republika] = First Faculty of Medicine, Charles University [Prague, Czech Republic]
12 Seoul National University Hospital
13 PSNREC - Neuropsychiatrie : recherche épidémiologique et clinique
14 CHRU Montpellier - Centre Hospitalier Régional Universitaire [Montpellier]
15 WWU - Westfälische Wilhelms-Universität Münster = University of Münster
16 Hôpital du Sacré-Coeur de Montréal
17 University of Oxford
18 Ospedale Bellaria [Bologna, Italy]
19 UQAM - Université du Québec à Montréal = University of Québec in Montréal
Ronald B. Postuma
  • Fonction : Auteur
McGill University = Université McGill [Montréal, Canada]
Alex Iranzo
  • Fonction : Auteur
Michele Hu
  • Fonction : Auteur
Birgit Högl
  • Fonction : Auteur
Innsbruck Medical University = Medizinische Universität Innsbruck
Bradley Boeve
  • Fonction : Auteur
Mayo Clinic [Rochester]
Raffaele Manni
  • Fonction : Auteur
Wolfgang Oertel
  • Fonction : Auteur
Philipps Universität Marburg = Philipps University of Marburg
Isabelle Arnulf
CHU Pitié-Salpêtrière [AP-HP]
Luigi Ferini-Strambi
Universita Vita Salute San Raffaele = Vita-Salute San Raffaele University [Milan, Italie]
Monica Puligheddu
Elena Antelmi
Alma Mater Studiorum Università di Bologna = University of Bologna
Valérie Cochen de Cock
Euromov
Dario Arnaldi
  • Fonction : Auteur
Università degli studi di Genova = University of Genoa
Brit Mollenhauer
University Medical Center Göttingen
Aleksandar Videnovic
Karel Sonka
1. lékařská fakulta, Univerzita Karlova [Praha, Česká republika] = First Faculty of Medicine, Charles University [Prague, Czech Republic]
Ki-Young Jung
  • Fonction : Auteur
Seoul National University Hospital
Dieter Kunz
  • Fonction : Auteur
Yves M Dauvilliers
  • Fonction : Auteur
Neuropsychiatrie : recherche épidémiologique et clinique
Centre Hospitalier Régional Universitaire [Montpellier]
Federica Provini
  • Fonction : Auteur
Simon Lewis
Jitka Buskova
  • Fonction : Auteur
Milena Pavlova
  • Fonction : Auteur
Anna Heidbreder
Westfälische Wilhelms-Universität Münster = University of Münster
Jacques Montplaisir
  • Fonction : Auteur
Hôpital du Sacré-Coeur de Montréal
Joan Santamaria
Euromov
Thomas Barber
University of Oxford
Ambra Stefani
Innsbruck Medical University = Medizinische Universität Innsbruck
Erik St Louis
  • Fonction : Auteur
Michele Terzaghi
  • Fonction : Auteur
Annette Janzen
  • Fonction : Auteur
Smandra Leu-Semenescu
  • Fonction : Auteur
CHU Pitié-Salpêtrière [AP-HP]
Guiseppe Plazzi
  • Fonction : Auteur
Flavio Nobili
  • Fonction : Auteur
Università degli studi di Genova = University of Genoa
Friederike Sixel-Doering
  • Fonction : Auteur
Petr Dusek
  • Fonction : Auteur
Frederik Bes
  • Fonction : Auteur
Pietro Cortelli
  • Fonction : Auteur
Ospedale Bellaria [Bologna, Italy]
Kaylena Ehgoetz Martens
  • Fonction : Auteur
Jean-François Gagnon
  • Fonction : Auteur
Université du Québec à Montréal = University of Québec in Montréal
Carles Gaig
  • Fonction : Auteur
Marco Zucconi
  • Fonction : Auteur
Universita Vita Salute San Raffaele = Vita-Salute San Raffaele University [Milan, Italie]
Claudia Trenkwalder
  • Fonction : Auteur
Università degli studi di Genova = University of Genoa
Ziv Gan-Or
McGill University = Université McGill [Montréal, Canada]
Christine Lo
  • Fonction : Auteur
Michal Rolinski
  • Fonction : Auteur
University of Oxford
Philip Mahlknecht
  • Fonction : Auteur
Evi Holzknecht
  • Fonction : Auteur
Angel Boeve
  • Fonction : Auteur
Luke Teigen
  • Fonction : Auteur
Gianpaolo Toscano
  • Fonction : Auteur
Geert Mayer
Silvia Morbelli
  • Fonction : Auteur
Università degli studi di Genova = University of Genoa
Benjamin Dawson
  • Fonction : Auteur
Amélie Pelletier
  • Fonction : Auteur
Hôpital du Sacré-Coeur de Montréal
Erik St.Louis
  • Fonction : Auteur

Résumé

Idiopathic REM sleep behaviour disorder (iRBD) is a powerful early sign of Parkinson's disease, dementia with Lewy bodies, and multiple system atrophy. This provides an unprecedented opportunity to directly observe prodromal neurodegenerative states, and potentially intervene with neuroprotective therapy. For future neuroprotective trials, it is essential to accurately estimate phenoconversion rate and identify potential predictors of phenoconversion. This study assessed the neurodegenerative disease risk and predictors of neurodegeneration in a large multicentre cohort of iRBD. We combined prospective follow-up data from 24 centres of the International RBD Study Group. At baseline, patients with polysomnographically-confirmed iRBD without parkinsonism or dementia underwent sleep, motor, cognitive, autonomic and special sensory testing. Patients were then prospectively followed, during which risk of dementia and parkinsonsim were assessed. The risk of dementia and parkinsonism was estimated with Kaplan-Meier analysis. Predictors of phenoconversion were assessed with Cox proportional hazards analysis, adjusting for age, sex, and centre. Sample size estimates for disease-modifying trials were calculated using a time-to-event analysis. Overall, 1280 patients were recruited. The average age was 66.3 ± 8.4 and 82.5% were male. Average follow-up was 4.6 years (range = 1-19 years). The overall conversion rate from iRBD to an overt neurodegenerative syndrome was 6.3% per year, with 73.5% converting after 12-year follow-up. The rate of phenoconversion was significantly increased with abnormal quantitative motor testing [hazard ratio (HR) = 3.16], objective motor examination (HR = 3.03), olfactory deficit (HR = 2.62), mild cognitive impairment (HR = 1.91-2.37), erectile dysfunction (HR = 2.13), motor symptoms (HR = 2.11), an abnormal DAT scan (HR = 1.98), colour vision abnormalities (HR = 1.69), constipation (HR = 1.67), REM atonia loss (HR = 1.54), and age (HR = 1.54). There was no significant predictive value of sex, daytime somnolence, insomnia, restless legs syndrome, sleep apnoea, urinary dysfunction, orthostatic symptoms, depression, anxiety, or hyperechogenicity on substantia nigra ultrasound. Among predictive markers, only cognitive variables were different at baseline between those converting to primary dementia versus parkinsonism. Sample size estimates for definitive neuroprotective trials ranged from 142 to 366 patients per arm. This large multicentre study documents the high phenoconversion rate from iRBD to an overt neurodegenerative syndrome. Our findings provide estimates of the relative predictive value of prodromal markers, which can be used to stratify patients for neuroprotective trials.

Domaines

Neurosciences [q-bio.NC] Médecine humaine et pathologie

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https://hal.umontpellier.fr/hal-02886582

Soumis le : mercredi 1 juillet 2020-16:12:57

Dernière modification le : mercredi 11 septembre 2024-20:12:11

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Dates et versions

hal-02886582 , version 1 (01-07-2020)

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Ronald B. Postuma, Alex Iranzo, Michele Hu, Birgit Högl, Bradley Boeve, et al.. Risk and predictors of dementia and parkinsonism in idiopathic REM sleep behaviour disorder: a multicentre study. Brain - A Journal of Neurology , 2019, 142 (3), pp.744-759. ⟨10.1093/brain/awz030⟩. ⟨hal-02886582⟩

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