Multicenter Study

. 2025 Sep;39(9):879-891.

doi: 10.1007/s40263-025-01193-5. Epub 2025 May 25.

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

Aymeric Lanore¹, Edouard Januel^{2

3}, Nathalie Bertille³, Margherita Fabbri⁴, Louise-Laure Mariani^{2

5}, Graziella Mangone², Sara Sambin², Poornima Jayadev Menon², Melissa Tir⁶, Matthieu Bereau⁷, Wassilios G Meissner⁸, Claire Thiriez⁹, Ana Marques¹⁰, Philippe Remy¹¹, Gwendoline Dupont¹², Elena Moro¹³, Luc Defebvre^{14

15}, Jean Luc Houeto¹⁶, Stéphane Thobois^{17

18}, Jean-Philippe Azulay¹⁹, Christian Geny²⁰, Solène Frismand²¹, Philippe Damier²², Caroline Giordana²³, Giovanni Castelnovo²⁴, Solène Ansquer²⁵, Anne Doe De Maindreville²⁶, Sophie Drapier²⁷, David Maltête²⁸, Christine Tranchant²⁹, Olivier Rascol⁴, Florence Tubach³, Yann De Rycke³, Jean-Christophe Corvol²; French NS-Park Network

Affiliations

¹ 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.
² 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.
³ 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.
⁴ 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.
⁵ Assistance Publique Hôpitaux de Paris, Department of Pharmacology, Hôpital Pitié-Salpêtrière, Paris, France.
⁶ Department of Neurology, NS-Park/FCRIN network, Amiens University Hospital, Amiens, France.
⁷ Department of Neurology, Hôpital Jean Minjoz, Besançon, France.
⁸ CHU Bordeaux, Service de Neurologie des Maladies Neurodégénératives, IMNc, NS-Park/FCRIN Network, 33000, Bordeaux, France.
⁹ Department of Neurology, NS-Park/FCRIN Network, CHU Caen, Caen, France.
¹⁰ Department of Neurology, CHU Clermont-Ferrand, Clermont-Ferrand, France.
¹¹ 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.
¹² Department of Neurology, François Mitterrand University Hospital, University de Bourgogne, Dijon, France.
¹³ Division of Neurology, Movement Disorders Unit, CHU de Grenoble, Grenoble Institute of Neurosciences, Grenoble Alpes University, Grenoble, France.
¹⁴ Service de Neurologie et Pathologie du Mouvement, Pôle de Neurosciences et Appareil Locomoteur, CHRU de Lille, Lille, France.
¹⁵ INSERM UMR 1171, LILLE France, Troubles Cognitifs Dégénératifs et Vasculaires, Lille, France.
¹⁶ 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.
¹⁷ 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.
¹⁸ INSERM, Centre de Recherche en Neurosciences de Lyon, PATH-PARK, Bron, France.
¹⁹ Department of Neurology and Movement Disorders, NS-Park/FCRIN Network; APHM, Hôpital Universitaire Timone, 13005, Marseille, France.
²⁰ Centre Expert Maladie de Parkinson, Service de Neurologie, Hôpital Gui de Chauliac, Montpellier, France.
²¹ Department of Neurology, NS-Park/FCRIN Network, University Hospital of Nancy, Nancy, France.
²² CHU de Nantes, CIC1413, Nantes & Université de Nantes, UFR Médecine, Nantes, France.
²³ Neurology Department, NS-Park/FCRIN Network, Centre Hospitalier Universitaire de Nice, Université Côte d'Azur, Nice, France.
²⁴ Department of Neurology, NS-Park/FCRIN Network; CHU de Nîmes, Nîmes, France.
²⁵ Department of Neurology, University Hospital of Poitiers; INSERM-CIC1402, Poitiers, France.
²⁶ Department of Neurology, NS-park/FCRIN Network, CHU Reims, Reims, France.
²⁷ Department of Neurology, CIC INSERM 1414, Pontchaillou University Hospital, Rennes, France.
²⁸ 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.
²⁹ 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.

PMID: 40415148
DOI: 10.1007/s40263-025-01193-5

Multicenter Study

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

Aymeric Lanore et al. CNS Drugs. 2025 Sep.

. 2025 Sep;39(9):879-891.

doi: 10.1007/s40263-025-01193-5. Epub 2025 May 25.

Authors

Affiliations

¹ 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.
² 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.
³ 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.
⁴ 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.
⁵ Assistance Publique Hôpitaux de Paris, Department of Pharmacology, Hôpital Pitié-Salpêtrière, Paris, France.
⁶ Department of Neurology, NS-Park/FCRIN network, Amiens University Hospital, Amiens, France.
⁷ Department of Neurology, Hôpital Jean Minjoz, Besançon, France.
⁸ CHU Bordeaux, Service de Neurologie des Maladies Neurodégénératives, IMNc, NS-Park/FCRIN Network, 33000, Bordeaux, France.
⁹ Department of Neurology, NS-Park/FCRIN Network, CHU Caen, Caen, France.
¹⁰ Department of Neurology, CHU Clermont-Ferrand, Clermont-Ferrand, France.
¹¹ 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.
¹² Department of Neurology, François Mitterrand University Hospital, University de Bourgogne, Dijon, France.
¹³ Division of Neurology, Movement Disorders Unit, CHU de Grenoble, Grenoble Institute of Neurosciences, Grenoble Alpes University, Grenoble, France.
¹⁴ Service de Neurologie et Pathologie du Mouvement, Pôle de Neurosciences et Appareil Locomoteur, CHRU de Lille, Lille, France.
¹⁵ INSERM UMR 1171, LILLE France, Troubles Cognitifs Dégénératifs et Vasculaires, Lille, France.
¹⁶ 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.
¹⁷ 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.
¹⁸ INSERM, Centre de Recherche en Neurosciences de Lyon, PATH-PARK, Bron, France.
¹⁹ Department of Neurology and Movement Disorders, NS-Park/FCRIN Network; APHM, Hôpital Universitaire Timone, 13005, Marseille, France.
²⁰ Centre Expert Maladie de Parkinson, Service de Neurologie, Hôpital Gui de Chauliac, Montpellier, France.
²¹ Department of Neurology, NS-Park/FCRIN Network, University Hospital of Nancy, Nancy, France.
²² CHU de Nantes, CIC1413, Nantes & Université de Nantes, UFR Médecine, Nantes, France.
²³ Neurology Department, NS-Park/FCRIN Network, Centre Hospitalier Universitaire de Nice, Université Côte d'Azur, Nice, France.
²⁴ Department of Neurology, NS-Park/FCRIN Network; CHU de Nîmes, Nîmes, France.
²⁵ Department of Neurology, University Hospital of Poitiers; INSERM-CIC1402, Poitiers, France.
²⁶ Department of Neurology, NS-park/FCRIN Network, CHU Reims, Reims, France.
²⁷ Department of Neurology, CIC INSERM 1414, Pontchaillou University Hospital, Rennes, France.
²⁸ 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.
²⁹ 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.

PMID: 40415148
DOI: 10.1007/s40263-025-01193-5

Abstract

Background: 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.

Methods: 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.

Results: 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.

Conclusions: 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.

Gov identifier: NCT04888364. Registered June 2021.

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Conflict of interest statement

Declarations. Funding: The research leading to these results has received funding from the program ‘Investissements d’avenir’ ANR-10- IAIHU-06, French National Institute of Health and Medical Research (INSERM), Ministère des Solidarités et de la Santé – DGOS, Paris, France, and Agence nationale de la recherche, PIA 1 ‘INBS¡, F-CRIN, Paris, France. We are very grateful to the patients and family members who participated in the study. Conflicts of Interest: O.R. is an Editorial Board member of CNS Drugs. O.R. was not involved in the selection of peer reviewers for the manuscript nor any of the subsequent editorial decisions. The authors report no other competing interests. Ethics Approval: The study received approval from an ethical committee in June 2020 (CPPIDF1-2020-ND58) and authorisation from the CNIL in February 2021 (DR-2021-039). Consent to Participate: All patients received information about the study and had the opportunity to exercise their right to refuse participation through the cohort transparency website in accordance with EU General Protection Data Regulation rules ( https://parkinson.network/la-cohorte-ns-park ). Consent for Publication: Not applicable. Availability of Data and Material: The supporting data for this study are not publicly available owing to their proprietary nature. However, they can be provided upon reasonable request to the corresponding author, subject to compliance with applicable regulations and institutional policies. Code Availability: Not applicable. Author Contributions: A.L.: conceptualisation, data curation, formal analysis, methodology, visualisation, writing – original draft and writing – review and editing. E.J.: conceptualisation, methodology, statistical analysis support and critical review and editing. N.B.: database management, data curation and critical review. M.F., L.-L.M., G.M., S.S., P.J.M., M.T., M.B., W.G.M., C.T., A.M., P.R., G.D., E.M., L.D., J.L.H., S.T., J.-P.A., C.G., S.F., P.D., C.Gi., G.C, C.Ta., S.A., A.D.D.M., S.D., D.M. and C.Tra.: data acquisition and patient recruitment, critical review and editing. O.R., F.T., Y.D.R. and J.-C.C.: conceptualisation, supervision, methodology, statistical analysis support, critical review and editing.

References

1. Postuma RB, Berg D, Stern M, Poewe W, Olanow CW, Oertel W, et al. MDS clinical diagnostic criteria for Parkinson’s disease. Mov Disord. 2015;30(12):1591–601. - PubMed
1. Fox SH, Katzenschlager R, Lim SY, Barton B, de Bie RMA, Seppi K, et al. International Parkinson and movement disorder society evidence-based medicine review: update on treatments for the motor symptoms of Parkinson’s disease: treatment of motor symptoms in PD. Mov Disord. 2018;33(8):1248–66. - PubMed
1. Hauser RA. Factors associated with the development of motor fluctuations and dyskinesias in Parkinson disease. Arch Neurol. 2006;63(12):1756. - PubMed
1. Warren Olanow C, Kieburtz K, Rascol O, Poewe W, Schapira AH, Emre M, et al. Factors predictive of the development of Levodopa-induced dyskinesia and wearing-off in Parkinson’s disease. Mov Disord. 2013;28(8):1064–71. - PubMed
1. Fox SH, Katzenschlager R, Lim SY, Ravina B, Seppi K, Coelho M, et al. The Movement Disorder Society evidence-based medicine review update: treatments for the motor symptoms of Parkinson’s disease. Mov Disord. 2011;26(Suppl 3):S2-41. - PubMed

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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

Affiliations

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

Authors

Affiliations

Abstract

Conflict of interest statement

References

Publication types

MeSH terms

Substances

Associated data

Grants and funding

LinkOut - more resources

Full Text Sources

Medical

Miscellaneous