Risk and course of motor complications in a population-based incident Parkinson's disease cohort
Introduction
Parkinson disease (PD) is a relentlessly progressive movement disorder of unknown etiology [1]. With PD progression, the efficacy of pharmacotherapy deteriorates [2] and patients may develop motor complications, which can be broadly subdivided into motor fluctuations and dyskinesias. The risk for and time to emergence of these motor complications vary substantially among patients for reasons that are probably complex, including both disease- and drug-related factors, particularly treatment with levodopa [3], [4].
Although motor fluctuations and dyskinesias may compromise quality of life [5], their evolution and prognosis are still incompletely investigated, as most previous studies assessed cross-sectional cohorts with established disease [6] or followed patients recruited from movement disorders centers or clinical trials [7]. This may result in both under- and overestimation of the risk of these motor complications. In addition, as treatment options have changed during the last decades, previous estimates might no longer be accurate. Finally, device-aided therapies have emerged as second-line treatments in patients with otherwise intractable motor complications [8], [9]. Recent studies promote early initiation of these advanced therapies [9], [10], which – however – are costly and may cause serious adverse events. Therefore, precise information on the evolution and potential reversal of motor fluctuations and dyskinesias using conventional pharmacotherapy is crucial for optimal patient selection to and timing of second-line treatment in PD.
To gain this important knowledge, we recruited a large, population-based, and initially drug-naive PD cohort that we monitored closely for emergence of motor complications for five years from diagnosis.
Section snippets
Subjects
All subjects participate in the Norwegian ParkWest project, a prospective, population-based, multicenter, longitudinal cohort study investigating the incidence, neurobiology and prognosis of PD. In order to establish a population-representative, incident PD cohort, we recruited patients with newly-diagnosed and untreated PD from the general population between November, 2004, and August, 2006, using multiple recruitment strategies, as previously described [11]. Briefly, all patients were
Baseline characteristics and subject flow
Baseline characteristics are given in Table 1 and the flow of subjects in Fig. 1. Of the 189 patients included at baseline, 183 (97%) completed 1 year, 173 (92%) 3 years and 158 (84%) 5 years of biannual follow-up, generating 1911 observations in total. Few subjects (7/189, 4%) withdrew from the study, whereas remaining loss to follow-up (24/189, 13%) was due to death. Median follow-up time was 5.0 (interquartile range 4.9–5.1) years.
Frequency of motor complications
Point prevalence rates increased progressively, reaching
Discussion
Our study highlights a high risk of early motor complications in the general PD population and also provides important insights into their evolution and associated risk factors, with implications for both understanding and management of motor fluctuations and dyskinesias in PD.
We are aware of only two previous longitudinal studies of dyskinesias [16] or motor complications [17] in patients with early PD derived from the community. Our study differs importantly from these in several ways,
Funding
This study was supported by the Research Council of Norway (grant# 177966), the Western Norway Regional Health Authority (grant# 911218 and 911949), and the Norwegian Parkinson's disease Association. Sponsors had no role in study design; the collection, analysis and interpretation of data; in the writing of the report; or in the decision to submit the article for publication.
Financial disclosures
Anders Bjornestad reports no disclosures.
Elin Bjelland Forsaa reports no disclosures.
Kenn Freddy Pedersen reports no disclosures.
Ole-Bjørn Tysnes reports no disclosures.
Jan Petter Larsen reports no disclosures.
Guido Alves has received payment for lecturing from AbbVie and research support from the Norwegian Parkinson's Disease Association.
Author’s roles
Study concept and design: Drs. Bjornestad, Tysnes, Larsen, Alves.
Acquisition, analysis, or interpretation of data: All authors.
Drafting of the manuscript: Dr. Bjornestad.
Critical revision of the manuscript for important intellectual content: All authors.
Statistical analysis: Drs. Bjornestad, Alves.
Obtained funding: Dr. Larsen
Administrative, technical, or material support: Drs. Tysnes, Larsen.
Study supervision: Drs. Tysnes, Larsen.
Dr. Bjornestad takes responsibility for the integrity of the data
Acknowledgments
We are grateful to all patients for their participation in this study and thank the members of the Norwegian ParkWest study group and all other personnel involved in this study for their contributions.
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