한빛사논문
- 조회350
Seong Ho Jeong 1,2, Hye Sun Lee 3, Seok Jong Chung 1,4, Han Soo Yoo 1, Jin Ho Jung 5, Kyoungwon Baik 1, Yang Hyun Lee 1, Young H Sohn 1, Phil Hyu Lee 1,6,*
1Department of Neurology, Yonsei University College of Medicine, Seoul, South Korea.
2Department of Neurology, Sanggye Paik Hospital, Inje University College of Medicine, Seoul, South Korea.
3Biostatistics Collaboration Unit, Yonsei University College of Medicine, Seoul, South Korea.
4Department of Neurology, Yongin Severance Hospital, Yonsei University Health System, Yongin, South Korea.
5Department of Neurology, Busan Paik Hospital, Inje University College of Medicine, Busan, South Korea.
6Severance Biomedical Science Institute, Yonsei University College of Medicine, Seoul, South Korea.
*Corresponding author.
Abstract
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 prior 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 inter-group 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 statin had a lower baseline dopamine transporter availability in the anterior (2.13 ± 0.55 vs. 2.37 ± 0.67; p = 0.002), posterior (1.31 ± 0.43 vs. 1.49 ± 0.54; p = 0.003), and ventral putamina (1.40 ± 0.39 vs. 1.56 ± 0.47; p = 0.002) than that in matched patients with Parkinson's disease without statin. After adjusting for age at symptom onset, sex, disease duration and vascular risk factors, linear regression models showed that a prior treatment of statin 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 statin had a faster longitudinal increase in levodopa-equivalent dose than those without statin. A survival analysis showed that the rate of dementia conversion was significantly higher in patients with Parkinson's disease with statin (hazard ratio, 2.019; 95% CI, 1.108 - 3.678; P = 0.022) than those without statin. 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.
논문정보
- Research article
- 2021년 08월 (BRIC 등록일 2021-08-18)
- 국내 연구진
- 의약학 > 신경의학
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