Background and ObjectivesThe burden of cerebrovascular disease pathologies is associated with progressive parkinsonism in older adults. We tested the hypothesis that older adults using statins have a lower risk of developing parkinsonism.MethodsWe studied older adults with annual clinical testing of 4 parkinsonian signs and assessment of statin use based on inspection of all medications. Parkinsonism was present if there was clinical evidence of ≥2 parkinsonian signs. Postmortem brain examination collected indices of pathologies, including atherosclerosis of the large vessels of the circle of Willis. We examined whether baseline statin use was related to incident parkinsonism. Then in decedents, we examined whether statin use before death was related to pathologies and whether pathologies linked the association of statin use to parkinsonism.ResultsMean age of the participants (n = 2,841) at study baseline was 76.3 years (SD 7.4 years), and 75% were women. During an average follow-up of 6 years (mean 5.6 years, SD 4.9 years), 50% (n = 1,432) of participants developed parkinsonism. Statin use at baseline (n = 936) was associated with a lower risk of parkinsonism (hazard ratio 0.84, 95% CI 0.74–0.96, p = 0.008), controlling for demographics, vascular risk factors, and diseases. Among the decedents (n = 1,044, mean age at death 89.2 years, SD 6.7 years), statin use before death was associated with a lower odds of atherosclerosis (odds ratio [OR] 0.63, 95% CI 0.50–0.79, p < 0.001). In a mediation analysis, both a direct (OR 0.73, 95% CI 0.54–0.93, p = 0.008) and an indirect (OR 0.92, 95% CI 0.88–0.97, p = 0.002) pathway via less severe atherosclerosis linked statins to parkinsonism, indicating that atherosclerosis mediated 17% of the association between statins and parkinsonism.DiscussionAdults using statins have a lower risk of parkinsonism that may be partially mediated by a lower odds of brain atherosclerosis. These findings highlight the role of cerebrovascular pathologies in late-life parkinsonism and suggest a potential role for statins in decreasing its magnitude.Classification of EvidenceThis study provides Class I evidence that statin use is associated with a lower risk of parkinsonism in older adults.