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Lack of Association Between GBA Mutations and Motor Complications in European and American Parkinson’s Disease Cohorts
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...
Autores principales: | , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
IOS Press
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8609705/ https://www.ncbi.nlm.nih.gov/pubmed/34275908 http://dx.doi.org/10.3233/JPD-212657 |
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author | Maple-Grødem, Jodi 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 |
author_facet | Maple-Grødem, Jodi 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 |
author_sort | Maple-Grødem, Jodi |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-8609705 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | IOS Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-86097052021-12-10 Lack of Association Between GBA Mutations and Motor Complications in European and American Parkinson’s Disease Cohorts Maple-Grødem, Jodi 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 J Parkinsons Dis Michael J. Fox Foundation – Replication Paper 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. IOS Press 2021-10-12 /pmc/articles/PMC8609705/ /pubmed/34275908 http://dx.doi.org/10.3233/JPD-212657 Text en © 2021 – The authors. Published by IOS Press https://creativecommons.org/licenses/by-nc/4.0/This is an open access article distributed under the terms of the Creative Commons Attribution Non-Commercial (CC BY-NC 4.0) License (https://creativecommons.org/licenses/by-nc/4.0/) , which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Michael J. Fox Foundation – Replication Paper Maple-Grødem, Jodi 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 Lack of Association Between GBA Mutations and Motor Complications in European and American Parkinson’s Disease Cohorts |
title | Lack of Association Between GBA Mutations and Motor Complications in European and American Parkinson’s Disease Cohorts |
title_full | Lack of Association Between GBA Mutations and Motor Complications in European and American Parkinson’s Disease Cohorts |
title_fullStr | Lack of Association Between GBA Mutations and Motor Complications in European and American Parkinson’s Disease Cohorts |
title_full_unstemmed | Lack of Association Between GBA Mutations and Motor Complications in European and American Parkinson’s Disease Cohorts |
title_short | Lack of Association Between GBA Mutations and Motor Complications in European and American Parkinson’s Disease Cohorts |
title_sort | lack of association between gba mutations and motor complications in european and american parkinson’s disease cohorts |
topic | Michael J. Fox Foundation – Replication Paper |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8609705/ https://www.ncbi.nlm.nih.gov/pubmed/34275908 http://dx.doi.org/10.3233/JPD-212657 |
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