Effects of statins on dopamine loss and prognosis in Parkinson's disease
Effects of statins on dopamine loss and prognosis in Parkinson's disease
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DOI：
10.1093/brain/awab292
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发表时间：
2021-08-04
期刊：
影响因子：
14.5
通讯作者：
Lee, Phil Hyu
中科院分区：
文献类型：
--
作者：
Jeong, Seong Ho;Lee, Hye Sun;Lee, Phil Hyu
他汀类药物不仅被广泛用于心血管疾病的一级和二级预防，阻断胆固醇生物合成，而且由于其多效性作用，也被广泛用于神经系统疾病期间的潜在神经保护剂。在这项研究中，我们调查是否以前使用他汀类药物的影响基线黑质纹状体多巴胺的损失在诊断时，纵向运动和认知结果的帕金森病patients.Five百药物初治帕金森病患者进行多巴胺转运蛋白成像分为两组，根据以前使用他汀类药物：患者和不使用他汀类药物。多元线性回归用于确定多巴胺转运蛋白可用性的组间差异。我们分别使用线性混合模型和生存分析评估了两组之间左旋多巴等效剂量和痴呆转换的纵向变化。此外，中介分析被应用于检查总胆固醇的影响。帕金森病患者接受他汀类药物治疗，其前额叶多巴胺转运蛋白的基线可用性较低，（2.13 ± 0.55 vs 2.37 ± 0.67; P = 0.002），后（1.31 +/- 0.43对1.49 +/- 0.54; P = 0.003）和腹侧壳核（1.40 +/- 0.39对1.56 +/- 0.47; P = 0.002）的比例高于未使用他汀类药物的帕金森病患者。在校正了症状发作时的年龄、性别、病程和血管危险因素后，线性回归模型显示，既往使用他汀类药物治疗与前壳核中多巴胺转运蛋白可用性的严重降低显著相关，（Beta =-0.140，P = 0.004）、后壳核（Beta =-0.162，P = 0.001）和腹壳核（Beta =-0.140，P = 0.004）。线性混合模型显示，帕金森病患者接受他汀类药物治疗时，左旋多巴等效剂量的纵向增加速度比未接受他汀类药物治疗的患者快。一项生存分析显示，与未使用他汀类药物的帕金森病患者相比，使用他汀类药物的帕金森病患者的痴呆转换率显著更高（风险比，2.019; 95%置信区间，1.108-3.678; P = 0.022）。中介分析显示，他汀类药物治疗对基线多巴胺转运蛋白利用率和纵向结局的影响不受总胆固醇水平的介导。这项研究表明，他汀类药物的使用可能对帕金森病患者的黑质纹状体多巴胺变性和长期预后产生不利影响。
Statins are more widely used not only for the primary and secondary prevention of cardiovascular disease blocking cholesterol biosynthesis but also for the potential neuroprotective agents during neurological disorders due to their pleiotropic effects. In this study, we investigate whether the previous use of statins affect baseline nigrostriatal dopamine loss at the time of diagnosis and longitudinal motor and cognitive outcomes in patients with Parkinson's disease.Five hundred drug-naive patients with Parkinson's disease who underwent dopamine transporter imaging were classified into two groups according to the prior use of statins: patients with and without statin use. Multivariate linear regression was used to determine intergroup differences in dopamine transporter availability. We evaluated the longitudinal changes in levodopa-equivalent dose and dementia conversion between the groups using a linear mixed model and survival analysis, respectively. In addition, mediation analysis was applied to examine the effect of total cholesterol.Patients with Parkinson's disease treated with statins had a lower baseline dopamine transporter availability in the anterior (2.13 +/- 0.55 versus 2.37 +/- 0.67; P = 0.002), posterior (1.31 +/- 0.43 versus 1.49 +/- 0.54; P = 0.003) and ventral putamina (1.40 +/- 0.39 versus 1.56 +/- 0.47; P = 0.002) than that in matched patients with Parkinson's disease without statins. After adjusting for age at symptom onset, sex, disease duration and vascular risk factors, linear regression models showed that a previous treatment with statins remained significantly and independently associated with more severely decreased dopamine transporter availability in the anterior putamen (Beta = -0.140, P = 0.004), posterior putamen (Beta = -0.162, P = 0.001) and ventral putamen (Beta = -0.140, P = 0.004). A linear mixed model revealed that patients with Parkinson's disease being treated with statins had a faster longitudinal increase in levodopa-equivalent dose than those without. A survival analysis showed that the rate of dementia conversion was significantly higher in patients with Parkinson's disease with statins (hazard ratio, 2.019; 95% confidence interval, 1.108-3.678; P = 0.022) than those without. Mediation analyses revealed that the effect of statin treatment on baseline dopamine transporter availability and longitudinal outcome was not mediated by total cholesterol levels. This study suggests that statin use may have a detrimental effect on baseline nigrostriatal dopamine degeneration and long-term outcomes in patients with Parkinson's disease.