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Progression of clinical markers in prodromal Parkinson's disease and dementia with Lewy bodies: a multicentre study

S. Joza, MT. Hu, KY. Jung, D. Kunz, A. Stefani, P. Dušek, M. Terzaghi, D. Arnaldi, A. Videnovic, MC. Schiess, W. Hermann, JY. Lee, L. Ferini-Strambi, SJG. Lewis, L. Leclair-Visonneau, WH. Oertel, E. Antelmi, F. Sixel-Döring, V. Cochen De Cock, C....

. 2023 ; 146 (8) : 3258-3272. [pub] 2023Aug01

Jazyk angličtina Země Anglie, Velká Británie

Typ dokumentu multicentrická studie, časopisecké články, práce podpořená grantem

Perzistentní odkaz   https://www.medvik.cz/link/bmc23016775

The neurodegenerative synucleinopathies, including Parkinson's disease and dementia with Lewy bodies, are characterized by a typically lengthy prodromal period of progressive subclinical motor and non-motor manifestations. Among these, idiopathic REM sleep behaviour disorder is a powerful early predictor of eventual phenoconversion, and therefore represents a critical opportunity to intervene with neuroprotective therapy. To inform the design of randomized trials, it is essential to study the natural progression of clinical markers during the prodromal stages of disease in order to establish optimal clinical end points. In this study, we combined prospective follow-up data from 28 centres of the International REM Sleep Behavior Disorder Study Group representing 12 countries. Polysomnogram-confirmed REM sleep behaviour disorder subjects were assessed for prodromal Parkinson's disease using the Movement Disorder Society criteria and underwent periodic structured sleep, motor, cognitive, autonomic and olfactory testing. We used linear mixed-effect modelling to estimate annual rates of clinical marker progression stratified by disease subtype, including prodromal Parkinson's disease and prodromal dementia with Lewy bodies. In addition, we calculated sample size requirements to demonstrate slowing of progression under different anticipated treatment effects. Overall, 1160 subjects were followed over an average of 3.3 ± 2.2 years. Among clinical variables assessed continuously, motor variables tended to progress faster and required the lowest sample sizes, ranging from 151 to 560 per group (at 50% drug efficacy and 2-year follow-up). By contrast, cognitive, olfactory and autonomic variables showed modest progression with higher variability, resulting in high sample sizes. The most efficient design was a time-to-event analysis using combined milestones of motor and cognitive decline, estimating 117 per group at 50% drug efficacy and 2-year trial duration. Finally, while phenoconverters showed overall greater progression than non-converters in motor, olfactory, cognitive and certain autonomic markers, the only robust difference in progression between Parkinson's disease and dementia with Lewy bodies phenoconverters was in cognitive testing. This large multicentre study demonstrates the evolution of motor and non-motor manifestations in prodromal synucleinopathy. These findings provide optimized clinical end points and sample size estimates to inform future neuroprotective trials.

Centre d'Études Avancées en Médecine du Sommeil Hôpital du Sacré Cœur de Montréal Montréal Quebec H4J 1C5 Canada

Clinic for Sleep and Chronomedicine St Hedwig Krankenhaus 10115 Berlin Germany

Clinical Neurophysiology Research Unit Oasi Research Institute IRCCS 94018 Troina Italy

Department of Biomedical and Neuromotor Sciences University of Bologna 40127 Bologna Italy

Department of Biomedical Metabolic and Neural Sciences University of Modena and Reggio Emilia 41121 Modena Italy

Department of Brain and Behavioral Sciences University of Pavia 27100 Pavia Italy

Department of Clinical Neurophysiology CHU de Nantes 44000 Nantes France

Department of Kinesiology and Health Sciences University of Waterloo Waterloo Ontario N2L 3G1 Canada

Department of Medical Surgical Sciences and Advanced Technologies GF Ingrassia University of Catania 95124 Catania Italy

Department of Neurology and Center of Clinical Neuroscience 1st Faculty of Medicine Charles University and General University Hospital 116 36 Prague Czech Republic

Department of Neurology and Section on Clinical Neuroscience Philipps University Marburg 35037 Marburg Germany

Department of Neurology and Sleep Beau Soleil Clinic 34070 Montpellier France

Department of Neurology Kangbuk Samsung Hospital 04514 Seoul Republic of Korea

Department of Neurology Massachusetts General Hospital Harvard Medical School Boston MA 02114 USA

Department of Neurology Montreal Neurological Institute Montreal Quebec H3A 2B4 Canada

Department of Neurology Ruijin Hospital Shanghai Jiao Tong University School of Medicine 200025 Shanghai China

Department of Neurology Seoul National University College of Medicine Seoul Metropolitan Government Seoul National University Boramae Medical Center 07061 Seoul South Korea

Department of Neurology Seoul National University College of Medicine Seoul National University Hospital 03080 Seoul Republic of Korea

Department of Neurology The University of Texas Health Science Center at Houston Houston TX 77030 USA

Department of Neurology University Hospital Bern 3010 Bern Switzerland

Department of Neurology University of Rostock 18147 Rostock Germany

Department of Neuroscience Rehabilitation Ophthalmology Genetics Maternal and Child Health Clinical Neurology University of Genoa 16132 Genoa Italy

Department of Neurosciences Biomedicine and Movement Sciences University of Verona 37121 Verona Italy

Department of Neurosurgery University Medical Center Goettingen 37075 Göttingen Germany

Department of Psychology Université du Québec à Montréal Montréal Quebec H2L 2C4 Canada

Department of Surgery and Medical Surgical Specialties University of Catania 95123 Catania Italy

EuroMov Digital Health in Motion University of Montpellier IMT Mines Ales 34090 Montpellier France

ForeFront Parkinson's Disease Research Clinic Brain and Mind Centre School of Medical Sciences University of Sydney Sydney NSW 2006 Australia

Institute for Neurogenomics Helmholtz Center for Health and Environment 85764 München Neuherberg Germany

IRCCS Istituto delle Scienze Neurologiche di Bologna 40127 Bologna Italy

IRCCS Ospedale Policlinico San Martino 16132 Genoa Italy

Medical University Innsbruck Department of Neurology 6020 Innsbruck Austria

Nantes Université Inserm TENS The Enteric Nervous System in Gut and Brain Diseases 44000 Nantes France

National Institute of Mental Health Klecany 3rd Faculty of Medicine Charles University 110 00 Prague Czech Republic

Neurology Unit University Hospital of Rome Tor Vergata 00133 Rome Italy

Nuffield Department of Clinical Neurosciences Division of Neurology and Oxford Parkinson's Disease Centre University of Oxford Oxford OX3 9DU UK

Paracelsus Elena Klinik Centre for Movement Disorders 34128 Kassel Germany

School of Social and Community Medicine Bristol Medical School University of Bristol Bristol BS8 1QU UK

Sleep Center Department of Medical Sciences and Public Health University of Cagliari 09124 Cagliari Italy

Sleep Disorders Center Vita Salute San Raffaele University 20132 Milan Italy

Sleep Medicine and Epilepsy Unit IRCCS Mondino Foundation 27100 Pavia Italy

Sleep Medicine Center Department of Systems Medicine University of Rome Tor Vergata 00133 Rome Italy

Sleep Unit Department of Neurology Hôpital Gui de Chauliac Montpellier F 34093 Cedex 5 France

Citace poskytuje Crossref.org

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