Abstract
BackgroundWhile experimental data provided some compelling evidence on the benefits of statins on dopaminergic neurons, observational studies reported conflicting results regarding the potential of statins to effect the risk of Parkinson’s disease (PD).ObjectivesTo evaluate the association between changes in statin adherence over time and PD risk.MethodsA population-based cohort of new statin users (ages 40-79, years 1999-2012) was derived from a large Israeli healthcare services organization. Data included history of statin purchases and low density lipoprotein cholesterol (LDL-C) levels. Personal statin adherence was measured annually by the proportion of days covered (PDC). PD was detected employing a drug-tracer approach. Stratified (by sex, LDL-C levels at baseline and age) Cox proportional hazards models with time-dependent covariates were used to compute adjusted Hazard Ratio (HR) with 95%CI.ResultsThe cohort included 232,877 individuals, 49.3% men. Mean age at first statin purchase was 56.5 (±9.8) years for men and 58.7 (±9.2) years for women. PDC distribution for the whole follow up period differed between men and women: medians 58.3% and 54.1% respectively. During a mean follow up of 7.6 (±3.4) years, 2,550 (1.1%) PD cases were identified. In a 1-year lagged analysis, we found no association between annual statin adherence and PD risk in all age-groups regardless of statin type and potency. Age-pooled HR (95%CI) for men and women with LDL-C levels at baseline ≤160mg/dL were: 0.99 (0.99-1.01), 1.01 (1.00-1.02); and for men and women with LDL-C >160mg/dL levels: 0.99 (0.98-1.01), 0.97 (0.98-1.01).ConclusionsOur findings suggest that statin adherence over time does not affect PD risk. Future studies should use large-scale cohorts and refining assessments of long-term profiles in statin adherence.
Highlights
Previous experimental studies demonstrated beneficial biochemical effects of statins on dopaminergic neurons, including suppressed formation of α-synuclein aggregation [1] and the development of Lewy-bodies in Parkinson’s disease (PD) as well as their anti-oxidant [1] and anti-inflammatory properties [1,2,3]
proportion of days covered (PDC) distribution for the whole follow up period differed between men and women: medians 58.3% and 54.1% respectively
In a 1year lagged analysis, we found no association between annual statin adherence and PD risk in all age-groups regardless of statin type and potency
Summary
Previous experimental studies demonstrated beneficial biochemical effects of statins on dopaminergic neurons, including suppressed formation of α-synuclein aggregation [1] and the development of Lewy-bodies in Parkinson’s disease (PD) as well as their anti-oxidant [1] and anti-inflammatory properties [1,2,3]. Most observational studies involving large populations (6,465-23,780) found no associations between statin use and PD risk [4,5,6,7], findings are inconsistent, varying from significant decrease (43%-63%) [8,9,10,11,12,13] to significant increase (two fold) [14] in the risk of PD occurrence. While experimental data provided some compelling evidence on the benefits of statins on dopaminergic neurons, observational studies reported conflicting results regarding the potential of statins to effect the risk of Parkinson’s disease (PD)
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