Lack of Association Between GBA Mutations and Motor Complications in European and American Parkinson's Disease Cohorts
Grødem, Jodi Maple; Paul, Kimberly C.; Dalen, Ingvild; Ngo, Kathie J.; Wong, Darice; Macleod, Angus D.; Counsell, Carl E.; Bäckström, David; Forsgren, Lars; Tysnes, Ole-Bjørn; Kusters, Cynthia D.J.; Fogel, Brent L.; Bronstein, Jeff M.; Ritz, Beate; Alves, Guido Werner
Peer reviewed, Journal article
Published version
Date
2021Metadata
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Original version
Maple-Grødem, J., Paul, K. C., Dalen, I., Ngo, K. J., Wong, D., Macleod, A. D., ... & Alves, G. (2021). Lack of association between GBA mutations and motor complications in European and American Parkinson’s disease cohorts. Journal of Parkinson's disease, 11(4), 1569-1578. 10.3233/JPD-212657Abstract
Background:
Motor complications are a consequence of the chronic dopaminergic treatment of Parkinson’s disease (PD) and include levodopa-induced dyskinesia (LIDs) and motor fluctuations (MF). Currently, evidence is on lacking whether patients with GBA-associated PD differ in their risk of developing motor complications compared to the general PD population.
Objective:
To evaluate the association of GBA carrier status with the development of LIDS and MFs from early PD.
Methods:
Motor complications were recorded prospectively in 884 patients with PD from four longitudinal cohorts using part IV of the UPDRS or MDS-UPDRS. Subjects were followed for up to 11 years and the associations of GBA mutations with the development of motor complications were assessed using parametric accelerated failure time models.
Results:
In 439 patients from Europe, GBA mutations were detected in 53 (12.1%) patients and a total of 168 cases of LIDs and 258 cases of MF were observed. GBA carrier status was not associated with the time to develop LIDs (HR 0.78, 95%CI 0.47 to 1.26, p = 0.30) or MF (HR 1.19, 95%CI 0.84 to 1.70, p = 0.33). In the American cohorts, GBA mutations were detected in 36 (8.1%) patients and GBA carrier status was also not associated with the progression to LIDs (HR 1.08, 95%CI 0.55 to 2.14, p = 0.82) or MF (HR 1.22, 95%CI 0.74 to 2.04, p = 0.43).
Conclusion:
This study does not provide evidence that GBA-carrier status is associated with a higher risk of developing motor complications. Publication of studies with null results is vital to develop an accurate summary of the clinical features that impact patients with GBA-associated PD.