Introduction
Parkinson’s disease (PD) is a progressive neurodegenerative disease with significant negative consequences on health and quality-of-life despite of pharmacotherapies [1,2]. While its etiology remains largely unknown, numerous factors have been associated with risk of PD [3]. Statins are indicated for primary and secondary prevention of atherosclerotic coronary and cerebrovascular events, but it has also been suggested that due to their pleiotropic effects they could modify the progression of neurodegenerative diseases [4]. Meta-analyses of observational studies have reported a lower risk of PD among statin users [5,6]. However, confounding by indication and healthy user effect might have affected on findings [7]. Furthermore, the inverse risk has not been unequivocally demonstrated, as four studies have shown an increased risk of PD in statin users [8-11]. Based on these earlier observations, studies in specific populations that can better account for confounding by indication are needed.
Risk of atherosclerotic events is particularly increased in persons with diabetes and the 2019 American College of Cardiology and American Heart Association guidelines recommend at least moderate-intensity statin therapy for all persons with diabetes aged 40–75 years old [12]. Persons with diabetes may also have an elevated risk of PD [13,14]. Therefore, investigation of PD risk factors in this population is needed. Yet, there are only few studies on the association of statin use and risk of PD in persons with diabetes, all three of them reporting lower risk of PD among statin users than nonusers [8-10]. However, in these studies even short-term statin exposure was associated with lower risk [8,10], two of the studies were based on same population [8,10], and one that was published as a short commentary in response to Lin et al. [8] compared risk of PD among users of simvastatin and metformin to metformin only users [9]. We investigated whether statin use in persons with diabetes is associated with a risk of PD and whether there is a dose-response relationship.