Objective: To examine whether incident statin use is associated with lower Parkinson’s disease (PD) incidence while considering the potential for reverse causation.

Background: Drug repurposing has recently emerged as a promising approach to identify potential PD treatments. Statins represent an interesting candidate [1]. However, the long prodromal phase of PD raises the issue of reverse causation which was rarely addressed in previous observational studies. Thus, additional studies with a long follow-up are needed.

Method: E3N is a French cohort study of 98,995 women recruited in 1990 and surveyed every 24-36 months through self-administered questionnaires on lifestyle, medical history and drug claims databases (since 2004) [2]. Incident users who initiated statins (any/lipophilic/hydrophilic) from 1/7/2004 (baseline) were identified by their Anatomical Therapeutic Chemical codes (C10AA, C10BA, C10BX) through linked drug claims databases. Incident PD cases were ascertained using multiple sources and validated by an expert panel [3]. The association of time-varying statin use with PD incidence until 31/12/2018 was assessed using time-varying Cox proportional hazards regression models with age as the time scale and adjusted for confounders. Several statin exposure indices were considered: ever use, cumulative dose/duration, mean daily dose. To address reverse causation, statin exposure was included in the models with a lag-time of 5 years, during which we assumed no impact of statin exposure on PD.

Results: Over 15 years of follow-up (mean=9.1 years) of 73,925 women aged 54-79 years, 524 developed PD. 18,759 (25.4%) women started using statins (lipophilic, 11,552 [15.6%]; hydrophilic, 11,198 [15.1%]). Ever use of any statin was not associated with PD incidence. Alternatively, ever use of lipophilic statins was significantly associated with decreased PD incidence (hazard ratio=0.70, 95% confidence interval=0.51-0.98) with a dose-response relation for the mean daily dose (p-linear trend=0.0212). There was no evidence of association for any of the indices of exposure to hydrophilic statins.

Conclusion: Use of lipophilic, but not hydrophilic, statins at least 5 years earlier was associated with lower incidence of PD, with a dose-repose relation for increasing mean daily dose of use. Further studies are needed to confirm the potential beneficial role of lipophilic statins in PD, with special reference to type and dose of statin.

References: 1. Yan, J., et al., Effect of statins on Parkinson’s disease: A systematic review and meta-analysis. Medicine (Baltimore), 2019. 98(12): p. e14852.
2. Clavel-Chapelon, F., Cohort Profile: The French E3N Cohort Study. Int J Epidemiol, 2015. 44(3): p. 801-9.
3. Canonico, M., et al., Incidence of Parkinson’s disease in French women from the E3N cohort study over 27 years of follow-up. European Journal of Epidemiology, 2022. doi: 10.1007/s10654-022-00851-y.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/statin-use-and-incidence-of-parkinsons-disease-in-women-from-the-french-e3n-cohort-study/