Motor and Non-motor Complications Following Different Early Therapies in Parkinson’s Disease: Longitudinal Analysis of Real-Life Clinical and Therapeutic Data from the French NS-PARK Cohort.

May 26, 2025

Experts: Aymeric Lanore,Edouard Januel,Nathalie Bertille,Margherita Fabbri,Louise-Laure Mariani,Graziella Mangone,Sara Sambin,Poornima Jayadev Menon,Melissa Tir,Matthieu Bereau,Wassilios G Meissner,Claire Thiriez,Ana Marques,Philippe Remy,Gwendoline Dupont,Elena Moro,Luc Defebvre,Jean Luc Houeto,Stéphane Thobois,Jean-Philippe Azulay,Christian Geny,Solène Frismand,Philippe Damier,Caroline Giordana,Giovanni Castelnovo,Solène Ansquer,Anne Doe De Maindreville,Sophie Drapier,David Maltête,Christine Tranchant,Olivier Rascol,Florence Tubach,Yann De Rycke,Jean-Christophe Corvol,

Levodopa, dopamine agonists (DA) and monoamine oxidase inhibitors (MAOI) are all approved first-line therapies for Parkinson’s disease (PD), as monotherapy or in combination. Data on their use in the early management of patients with PD in real-life are lacking. Our objective was to assess the impact of early therapeutic strategies on the development of motor and neuropsychiatric complications using a nationwide PD cohort.
NS-PARK is a cohort of patients with PD recruited between 2011 and 2021 from 26 expert centres for PD in France. We analysed the patients with less than 5-years disease duration and no motor complications at inclusion. We used interval censoring survival models to assess the associations between therapeutic strategies (levodopa monotherapy, levodopa alternative therapies or levodopa combinations) and motor fluctuations, dyskinesia, impulse control and related behaviours (ICRBs), apathy, psychosis/hallucination and daytime sleepiness. Analyses were adjusted for sex, age, disease duration, dopaminergic dose and disease severity.
We included 1722 patients (38.4% female, median age 67.7 years). At inclusion, 41% received levodopa monotherapy, 31% received levodopa alternative therapies and 28% received levodopa combinations. Compared with levodopa monotherapy, levodopa alternative therapies were associated with a lower dyskinesia risk (hazard ratio (HR) 0.48, 95% confidence interval (CI)[0.28-0.84]), but there was no significant difference in motor fluctuations. Both levodopa alternative and combinations therapies increased ICRBs risk (HR 4.06, 95% CI [2.48-6.67]; HR 5.16, 95% CI [3.00-8.86]) and decreased apathy risk (HR 0.36, 95% CI [0.26-0.49]; HR 0.52, 95% CI [0.39-0.69]). No association was found with psychosis/hallucination or daytime sleepiness.
In this real-life cohort, our data supported an association between levodopa alternative therapies and a lower risk of dyskinesia and apathy, but a higher risk of ICRBs compared with levodopa monotherapy.
NCT04888364. Registered June 2021.

© 2025. The Author(s), under exclusive licence to Springer Nature Switzerland AG.

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ABOUT THE EXPERTS

Aymeric Lanore,Edouard Januel,Nathalie Bertille,Margherita Fabbri,Louise-Laure Mariani,Graziella Mangone,Sara Sambin,Poornima Jayadev Menon,Melissa Tir,Matthieu Bereau,Wassilios G Meissner,Claire Thiriez,Ana Marques,Philippe Remy,Gwendoline Dupont,Elena Moro,Luc Defebvre,Jean Luc Houeto,Stéphane Thobois,Jean-Philippe Azulay,Christian Geny,Solène Frismand,Philippe Damier,Caroline Giordana,Giovanni Castelnovo,Solène Ansquer,Anne Doe De Maindreville,Sophie Drapier,David Maltête,Christine Tranchant,Olivier Rascol,Florence Tubach,Yann De Rycke,Jean-Christophe Corvol,

Aymeric Lanore

Department of Neurology, CIC Neurosciences, Hôpital Pitié-Salpêtrière, Sorbonne Université, Institut du Cerveau-Paris Brain Institute-ICM, Inserm, CNRS, Assistance Publique Hôpitaux de Paris, NS-Park/FCRIN Network, Paris, France. aymeric.lanore@icm-institute.org.

Edouard Januel

Department of Neurology, CIC Neurosciences, Hôpital Pitié-Salpêtrière, Sorbonne Université, Institut du Cerveau-Paris Brain Institute-ICM, Inserm, CNRS, Assistance Publique Hôpitaux de Paris, NS-Park/FCRIN Network, Paris, France.

Département de Santé Publique, Centre de Pharmacoépidémiologie (Cephepi), Sorbonne Université, INSERM, Institut Pierre Louis d’Epidémiologie et de Santé Publique, AP-HP, Hôpital Pitié Salpêtrière, CIC-1901, 75013, Paris, France.

Nathalie Bertille

Département de Santé Publique, Centre de Pharmacoépidémiologie (Cephepi), Sorbonne Université, INSERM, Institut Pierre Louis d’Epidémiologie et de Santé Publique, AP-HP, Hôpital Pitié Salpêtrière, CIC-1901, 75013, Paris, France.

Margherita Fabbri

Clinical Investigation Center CIC1436, Parkinson Expert Center, Department of Clinical, Pharmacology and Neuroscience, NS-Park/FCRIN Network, NeuroToul COEN Center, Toulouse, University Hospital, INSERM and University of Toulouse 3, Toulouse, France.

Louise-Laure Mariani

Department of Neurology, CIC Neurosciences, Hôpital Pitié-Salpêtrière, Sorbonne Université, Institut du Cerveau-Paris Brain Institute-ICM, Inserm, CNRS, Assistance Publique Hôpitaux de Paris, NS-Park/FCRIN Network, Paris, France.

Assistance Publique Hôpitaux de Paris, Department of Pharmacology, Hôpital Pitié-Salpêtrière, Paris, France.

Graziella Mangone

Department of Neurology, CIC Neurosciences, Hôpital Pitié-Salpêtrière, Sorbonne Université, Institut du Cerveau-Paris Brain Institute-ICM, Inserm, CNRS, Assistance Publique Hôpitaux de Paris, NS-Park/FCRIN Network, Paris, France.

Sara Sambin

Department of Neurology, CIC Neurosciences, Hôpital Pitié-Salpêtrière, Sorbonne Université, Institut du Cerveau-Paris Brain Institute-ICM, Inserm, CNRS, Assistance Publique Hôpitaux de Paris, NS-Park/FCRIN Network, Paris, France.

Poornima Jayadev Menon

Department of Neurology, CIC Neurosciences, Hôpital Pitié-Salpêtrière, Sorbonne Université, Institut du Cerveau-Paris Brain Institute-ICM, Inserm, CNRS, Assistance Publique Hôpitaux de Paris, NS-Park/FCRIN Network, Paris, France.

Melissa Tir

Department of Neurology, NS-Park/FCRIN network, Amiens University Hospital, Amiens, France.

Matthieu Bereau

Department of Neurology, Hôpital Jean Minjoz, Besançon, France.

Wassilios G Meissner

CHU Bordeaux, Service de Neurologie des Maladies Neurodégénératives, IMNc, NS-Park/FCRIN Network, 33000, Bordeaux, France.

Claire Thiriez

Department of Neurology, NS-Park/FCRIN Network, CHU Caen, Caen, France.

Ana Marques

Department of Neurology, CHU Clermont-Ferrand, Clermont-Ferrand, France.

Philippe Remy

Centre Expert Parkinson and NS-Park/FCRIN Network, CHU Henri Mondor, AP-HP et Equipe Neuropsychologie Interventionnelle, INSERM-IMRB, Faculté de Santé, Université Paris-Est Créteil et Ecole Normale Supérieure PSL Université, Créteil, France.

Gwendoline Dupont

Department of Neurology, François Mitterrand University Hospital, University de Bourgogne, Dijon, France.

Elena Moro

Division of Neurology, Movement Disorders Unit, CHU de Grenoble, Grenoble Institute of Neurosciences, Grenoble Alpes University, Grenoble, France.

Luc Defebvre

Service de Neurologie et Pathologie du Mouvement, Pôle de Neurosciences et Appareil Locomoteur, CHRU de Lille, Lille, France.

INSERM UMR 1171, LILLE France, Troubles Cognitifs Dégénératifs et Vasculaires, Lille, France.

Jean Luc Houeto

Department of Neurology, NS-Park/FCRIN Network, Limoges University Hospital, Inserm, U1094, EpiMaCT-Epidemiology of Chronic Diseases in Tropical Zone, Limoges University Hospital, 87042, Limoges, France.

Stéphane Thobois

Hospices Civils de Lyon, Hopital Neurologique Pierre Wertheimer, Department of Neurology C, NS-Park/FCRIN Network, Univ Lyon, Université Claude Bernard Lyon 1, Faculté de Médecine Lyon Sud Charles Mérieux, Lyon, France.

INSERM, Centre de Recherche en Neurosciences de Lyon, PATH-PARK, Bron, France.

Jean-Philippe Azulay

Department of Neurology and Movement Disorders, NS-Park/FCRIN Network; APHM, Hôpital Universitaire Timone, 13005, Marseille, France.

Christian Geny

Centre Expert Maladie de Parkinson, Service de Neurologie, Hôpital Gui de Chauliac, Montpellier, France.

Solène Frismand

Department of Neurology, NS-Park/FCRIN Network, University Hospital of Nancy, Nancy, France.

Philippe Damier

CHU de Nantes, CIC1413, Nantes & Université de Nantes, UFR Médecine, Nantes, France.

Caroline Giordana

Neurology Department, NS-Park/FCRIN Network, Centre Hospitalier Universitaire de Nice, Université Côte d’Azur, Nice, France.

Giovanni Castelnovo

Department of Neurology, NS-Park/FCRIN Network; CHU de Nîmes, Nîmes, France.

Solène Ansquer

Department of Neurology, University Hospital of Poitiers; INSERM-CIC1402, Poitiers, France.

Anne Doe De Maindreville

Department of Neurology, NS-park/FCRIN Network, CHU Reims, Reims, France.

Sophie Drapier

Department of Neurology, CIC INSERM 1414, Pontchaillou University Hospital, Rennes, France.

David Maltête

Department of Neurology, Rouen University Hospital and University of Rouen, France, INSERM U1239, Laboratory of Neuronal and Neuroendocrine Differentiation and Communication, NS-Park/FCRIN Network, Mont-Saint-Aignan, France.

Christine Tranchant

Service de Neurologie, NS-Park/FCRIN Network; Hôpitaux Universitaires de Strasbourg, Institut de Génétique et de Biologie Moléculaire et Cellulaire (IGBMC), INSERM-U964/CNRS-UMR7104/Université de Strasbourg, Fédération de Médecine Translationnelle de Strasbourg (FMTS), Strasbourg, France.

Olivier Rascol

Clinical Investigation Center CIC1436, Parkinson Expert Center, Department of Clinical, Pharmacology and Neuroscience, NS-Park/FCRIN Network, NeuroToul COEN Center, Toulouse, University Hospital, INSERM and University of Toulouse 3, Toulouse, France.

Florence Tubach

Département de Santé Publique, Centre de Pharmacoépidémiologie (Cephepi), Sorbonne Université, INSERM, Institut Pierre Louis d’Epidémiologie et de Santé Publique, AP-HP, Hôpital Pitié Salpêtrière, CIC-1901, 75013, Paris, France.

Yann De Rycke

Département de Santé Publique, Centre de Pharmacoépidémiologie (Cephepi), Sorbonne Université, INSERM, Institut Pierre Louis d’Epidémiologie et de Santé Publique, AP-HP, Hôpital Pitié Salpêtrière, CIC-1901, 75013, Paris, France.

Jean-Christophe Corvol

Department of Neurology, CIC Neurosciences, Hôpital Pitié-Salpêtrière, Sorbonne Université, Institut du Cerveau-Paris Brain Institute-ICM, Inserm, CNRS, Assistance Publique Hôpitaux de Paris, NS-Park/FCRIN Network, Paris, France.