他汀类药物与老年人脑动脉粥样硬化和帕金森病发病的相关性。
Association of Statins With Cerebral Atherosclerosis and Incident Parkinsonism in Older Adults.
机构信息
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.
出版信息
Neurology. 2022 May 10;98(19):e1976-e1984. doi: 10.1212/WNL.0000000000200182. Epub 2022 Mar 23.
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, = 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, < 0.001). In a mediation analysis, both a direct (OR 0.73, 95% CI 0.54-0.93, = 0.008) and an indirect (OR 0.92, 95% CI 0.88-0.97, = 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.
背景与目的
脑血管病病理学的负担与老年人进行性帕金森病有关。我们检验了这样一个假设，即使用他汀类药物的老年人发生帕金森病的风险较低。
方法
我们研究了每年进行 4 项帕金森病体征临床检测的老年人，并根据对所有药物的检查来评估他汀类药物的使用情况。如果存在≥2 项帕金森病体征的临床证据，则存在帕金森病。尸检时采集病理学指标，包括大脑 Willis 环大血管的动脉粥样硬化。我们研究了基线时使用他汀类药物是否与新发帕金森病有关。然后，在死者中，我们研究了死亡前使用他汀类药物是否与病理学有关，以及病理学是否将他汀类药物的使用与帕金森病联系起来。
结果
参与者（n=2841）在研究开始时的平均年龄为 76.3 岁（SD 7.4 岁），75%为女性。在平均 6 年（平均 5.6 年，SD 4.9 年）的随访期间，50%（n=1432）的参与者出现帕金森病。基线时使用他汀类药物（n=936）与帕金森病风险降低相关（风险比 0.84，95%CI 0.74-0.96， = 0.008），控制了人口统计学、血管危险因素和疾病因素。在死者中（n=1044，死亡时的平均年龄为 89.2 岁，SD 6.7 岁），死亡前使用他汀类药物与动脉粥样硬化的可能性降低相关（比值比[OR]0.63，95%CI 0.50-0.79， < 0.001）。在中介分析中，通过较少的严重动脉粥样硬化，他汀类药物与帕金森病之间的直接（OR 0.73，95%CI 0.54-0.93， = 0.008）和间接（OR 0.92，95%CI 0.88-0.97， = 0.002）途径均与帕金森病相关，表明动脉粥样硬化介导了他汀类药物与帕金森病之间 17%的关联。
讨论
使用他汀类药物的成年人患帕金森病的风险较低，这可能部分是由于大脑动脉粥样硬化的可能性降低所致。这些发现强调了脑血管病理学在老年帕金森病中的作用，并提示他汀类药物可能在降低其严重程度方面发挥作用。
证据分类
本研究提供了 I 级证据，表明他汀类药物的使用与老年人帕金森病的风险降低有关。
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