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Effects of statins on dopamine loss and prognosis in Parkinson's disease

 Seong Ho Jeong  ;  Hye Sun Lee  ;  Seok Jong Chung  ;  Han Soo Yoo  ;  Jin Ho Jung  ;  Kyoungwon Baik  ;  Yang Hyun Lee  ;  Young H Sohn  ;  Phil Hyu Lee 
 BRAIN, Vol.144(10) : 3191-3200, 2021-10 
Journal Title
Issue Date
Aged ; Corpus Striatum / diagnostic imaging ; Corpus Striatum / drug effects ; Corpus Striatum / metabolism* ; Dopamine / metabolism* ; Female ; Humans ; Hydroxymethylglutaryl-CoA Reductase Inhibitors / adverse effects ; Hydroxymethylglutaryl-CoA Reductase Inhibitors / pharmacology ; Hydroxymethylglutaryl-CoA Reductase Inhibitors / therapeutic use* ; Male ; Middle Aged ; Parkinson Disease / diagnostic imaging ; Parkinson Disease / drug therapy* ; Parkinson Disease / metabolism* ; Prognosis ; Retrospective Studies
Parkinson’s disease ; dopamine transporter imaging ; prognosis ; statin
Statins are more widely used not only for the primary and secondary prevention of cardiovascular disease by 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-naïve 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.
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1. College of Medicine (의과대학) > Dept. of Neurology (신경과학교실) > 1. Journal Papers
Yonsei Authors
Baik, Kyoungwon(백경원) ORCID logo https://orcid.org/0000-0001-7215-375X
Sohn, Young Ho(손영호) ORCID logo https://orcid.org/0000-0001-6533-2610
Yoo, Han Soo(유한수) ORCID logo https://orcid.org/0000-0001-7846-6271
Lee, Yang Hyun(이양현)
Lee, Phil Hyu(이필휴) ORCID logo https://orcid.org/0000-0001-9931-8462
Lee, Hye Sun(이혜선) ORCID logo https://orcid.org/0000-0001-6328-6948
Chung, Seok Jong(정석종) ORCID logo https://orcid.org/0000-0001-6086-3199
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