Lack of Association Between GBA Mutations and Motor Complications in European and American Parkinson's Disease Cohorts

Jodi Maple-Grodem*, Kimberly C. Paul, Ingvild Dalen, Kathie J. Ngo, Darice Wong, Angus D. Macleod, Carl E. Counsell, David Backstrom, Lars Forsgren, Ole-Bjorn Tysnes, Cynthia D. J. Kusters, Brent L. Fogel, Jeff M. Bronstein, Beate Ritz, Guido Alves

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

Abstract

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.

Original languageEnglish
Pages (from-to)1569-1578
Number of pages10
Journal Journal of Parkinson's Disease
Volume11
Issue number4
DOIs
Publication statusPublished - 12 Oct 2021

Keywords

  • GBA
  • Parkinson's disease
  • motor complications
  • dyskinesias
  • motor fluctuations
  • LEVODOPA-INDUCED DYSKINESIA
  • GLUCOCEREBROSIDASE MUTATIONS
  • CLINICAL-FEATURES
  • RISK
  • GENE
  • PROGRESSION
  • FREQUENCY
  • DEMENTIA
  • GENOTYPE
  • DECLINE

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