Charting Disease Trajectories from Isolated REM Sleep Behavior Disorder to Parkinson's Disease

Author:

Di Folco Cécile12345,Couronné Raphaël12345,Arnulf Isabelle23456ORCID,Mangone Graziella23456,Leu‐Semenescu Smaranda23456,Dodet Pauline23456ORCID,Vidailhet Marie23456ORCID,Corvol Jean‐Christophe23456ORCID,Lehéricy Stéphane23456,Durrleman Stanley12345ORCID

Affiliation:

1. Inria, Centre de Paris Paris France

2. Paris Brain Institute–ICM Paris France

3. Inserm Paris France

4. CNRS Paris France

5. Sorbonne Université Paris France

6. AP‐HP, Hôpital de la Pitié Salpêtrière Paris France

Abstract

AbstractBackgroundClinical presentation and progression dynamics are variable in patients with Parkinson's disease (PD). Disease course mapping is an innovative disease modelling technique that summarizes the range of possible disease trajectories and estimates dimensions related to onset, sequence, and speed of progression of disease markers.ObjectiveTo propose a disease course map for PD and investigate progression profiles in patients with or without rapid eye movement sleep behavioral disorders (RBD).MethodsData of 919 PD patients and 88 isolated RBD patients from three independent longitudinal cohorts were analyzed (follow‐up duration = 5.1; 95% confidence interval, 1.1–8.1] years). Disease course map was estimated by using eight clinical markers (motor and non‐motor symptoms) and four imaging markers (dopaminergic denervation).ResultsPD course map showed that the first changes occurred in the contralateral putamen 13 years before diagnosis, followed by changes in motor symptoms, dysautonomia, sleep—all before diagnosis—and finally cognitive decline at the time of diagnosis. The model showed earlier disease onset, earlier non‐motor and later motor symptoms, more rapid progression of cognitive decline in PD patients with RBD than PD patients without RBD. This pattern was even more pronounced in patients with isolated RBD with early changes in sleep, followed by cognition and non‐motor symptoms and later changes in motor symptoms.ConclusionsOur findings are consistent with the presence of distinct patterns of progression between patients with and without RBD. Understanding heterogeneity of PD progression is key to decipher the underlying pathophysiology and select homogeneous subgroups of patients for precision medicine. © 2023 International Parkinson and Movement Disorder Society.

Funder

Agence Nationale de la Recherche

Association France Parkinson

Fondation EDF

H2020 European Research Council

H2020 Health

Publisher

Wiley

Subject

Neurology (clinical),Neurology

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