Progression of clinical markers in prodromal Parkinson's disease and dementia with Lewy bodies: a multicentre study
Language English Country Great Britain, England Media print
Document type Multicenter Study, Journal Article, Research Support, Non-U.S. Gov't
PubMed
36881989
DOI
10.1093/brain/awad072
PII: 7071614
Knihovny.cz E-resources
- Keywords
- Parkinson’s disease, REM sleep behaviour disorder, dementia with Lewy bodies, evolution, prodromal stage,
- MeSH
- Biomarkers MeSH
- Lewy Body Disease * diagnosis MeSH
- Humans MeSH
- Parkinson Disease * complications diagnosis MeSH
- REM Sleep Behavior Disorder * diagnosis MeSH
- Prodromal Symptoms MeSH
- Disease Progression MeSH
- Prospective Studies MeSH
- Check Tag
- Humans MeSH
- Publication type
- Journal Article MeSH
- Multicenter Study MeSH
- Research Support, Non-U.S. Gov't MeSH
- Names of Substances
- Biomarkers MeSH
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.
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 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 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 University Hospital Bern 3010 Bern Switzerland
Department of Neurology University of Rostock 18147 Rostock Germany
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
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
Neurology Unit University Hospital of Rome Tor Vergata 00133 Rome Italy
Paracelsus Elena Klinik Centre for Movement Disorders 34128 Kassel Germany
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
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