Statin Use and Incidence of Parkinson's Disease in Women from the French E3N Cohort Study
Background Statins represent candidates for drug repurposing in Parkinson's disease (PD). Few studies examined the role of reverse causation, statin subgroups, and dose–response relations based on time‐varying exposures. Objectives We examined whether statin use is associated with PD incidence...
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Published in | Movement disorders Vol. 38; no. 5; pp. 854 - 865 |
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Main Authors | , , , , , , , , , , , , |
Format | Journal Article |
Language | English |
Published |
Hoboken, USA
John Wiley & Sons, Inc
01.05.2023
Wiley Subscription Services, Inc Wiley |
Subjects | |
Online Access | Get full text |
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Summary: | Background
Statins represent candidates for drug repurposing in Parkinson's disease (PD). Few studies examined the role of reverse causation, statin subgroups, and dose–response relations based on time‐varying exposures.
Objectives
We examined whether statin use is associated with PD incidence while attempting to overcome the limitations described previously, especially reverse causation.
Method
We used data from the E3N cohort study of French women (follow‐up, 2004–2018). Incident PD was ascertained using multiple sources and validated by experts. New statin users were identified through linked drug claims. We set up a nested case‐control study to describe trajectories of statin prescriptions and medical consultations before diagnosis. We used time‐varying multivariable Cox proportional hazards regression models to examine the statins–PD association. Exposure indexes included ever use, cumulative duration/dose, and mean daily dose and were lagged by 5 years to address reverse causation.
Results
The case‐control study (693 cases, 13,784 controls) showed differences in case‐control trajectories, with changes in the 5 years before diagnosis in cases. Of 73,925 women (aged 54–79 years), 524 developed PD and 11,552 started using statins in lagged analyses. Ever use of any statin was not associated with PD (hazard ratio [HR] = 0.87, 95% confidence interval [CI] = 0.67–1.11). Alternatively, ever use of lipophilic statins was significantly associated with lower PD incidence (HR = 0.70, 95% CI = 0.51–0.98), with a dose–response relation for the mean daily dose (P‐linear trend = 0.02). There was no association for hydrophilic statins.
Conclusion
Use of lipophilic statins at least 5 years earlier was associated with reduced PD incidence in women, with a dose–response relation for the mean daily dose. © 2023 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society. |
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Bibliography: | T.T.H.N. was supported by postdoctoral grants from The Michael J. Fox Foundation and the France Parkinson Association. E.C. was supported by postdoctoral grants from The Michael J. Fox foundation. F.A., S.E., P.T.‐B., I.A., and A.C.M.T. report no disclosures. M.‐C.B.‐R. received speaker fees in 2020 from Mayoli‐Spindler and Gilead outside the field of the present article. I.D. reports no disclosures. E.R. received honorarium for speeches from Orkyn Aguettant and Elivie and for participating in an advisory board from Allergan and has received research support from Merz‐Pharma, Orkyn, Aguettant, Elivie, Ipsen, Allergan, Everpharma, Fondation Desmarest, AMADYS ADCY5.org This project was funded by the Michael J. Fox Foundation for Parkinson's Research and the France Parkinson Association. French National Research Agency (ANR), Societé Française de Médecine Esthétique, and the Dystonia Medical Research Foundation. M.C. obtained a research grant from the ANR. A.E. has obtained research grants from Plan Ecophyto (French Ministry of Agriculture) and France Parkinson Association. The work reported in this article was performed during A.F.'s term as a visiting scientist at the International Agency for Research on Cancer. The authors declare no other relationships or activities that could appear to have influenced the submitted work. Relevant conflicts of interest/financial disclosures Funding agencies ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 |
ISSN: | 0885-3185 1531-8257 |
DOI: | 10.1002/mds.29349 |