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.