Shahram Oveisgharan1, Lei Yu1, Lisa L Barnes1, Sonal Agrawal1, Julie A Schneider1, David A Bennett1, Aron S Buchman1. 1. From the Rush Alzheimer's Disease Center (S.O., L.Y., L.L.B., S.A., J.A.S., D.A.B., A.S.B.), Department of Neurological Sciences (S.O., L.Y., L.L.B., J.A.S., D.A.B., A.S.B.), Department of Behavioral Sciences (L.L.B.), and Department of Pathology (S.A., J.A.S.), Rush University Medical Center, Chicago, IL.
Abstract
BACKGROUND AND OBJECTIVES: The 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. METHODS: We 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. RESULTS: Mean 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. DISCUSSION: Adults 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 EVIDENCE: This study provides Class I evidence that statin use is associated with a lower risk of parkinsonism in older adults.
BACKGROUND AND OBJECTIVES: The 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. METHODS: We 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. RESULTS: Mean 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. DISCUSSION: Adults 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 EVIDENCE: This study provides Class I evidence that statin use is associated with a lower risk of parkinsonism in older adults.
Authors: Aron S Buchman; Patricia A Boyle; Sue E Leurgans; Lisa L Barnes; David A Bennett Journal: Am J Geriatr Psychiatry Date: 2011-06 Impact factor: 4.105
Authors: Aron S Buchman; Lei Yu; Shahram Oveisgharan; Jose M Farfel; Julie A Schneider; David A Bennett Journal: J Gerontol A Biol Sci Med Sci Date: 2021-03-31 Impact factor: 6.053
Authors: Lisa L Barnes; Raj C Shah; Neelum T Aggarwal; David A Bennett; Julie A Schneider Journal: Curr Alzheimer Res Date: 2012-07 Impact factor: 3.498
Authors: Zoe Arvanitakis; Ana W Capuano; Sue E Leurgans; David A Bennett; Julie A Schneider Journal: Lancet Neurol Date: 2016-06-14 Impact factor: 44.182