Presynaptic dopamine depletion predicts levodopa-induced dyskinesia in de novo patients with Parkinson's disease

Abstract

Although presynaptic dopamine depletion has been considered essential for the development of levodopa-induced dyskinesia (LID) in patients with Parkinson’s disease (PD), this association has been difficult to demonstrate. It was investigated whether the magnitude of presynaptic dopamine depletion is a risk factor for the development of LID in this study by quantitatively analyzing 18F-FP-CIT positron emission tomography (PET) data. This retrospective cohort study enrolled a total of 127 drug-naïve de novo patients with PD who completed 18F-FP-CIT PET scanning at their initial evaluation. The patients visited our outpatient clinic every 3–6 months and had been followed for a minimum of 2 years since beginning dopaminergic medication. The predictive power of the 18F-FP-CIT uptake of striatal subregions and other clinical factors for the development of LID was evaluated using Cox proportional hazard models. During a mean follow-up period of 3.4 years, 35 patients with PD (27.6%) developed LID. Patients with LID showed less dopamine transporter (DAT) activity in the putamen than did those without LID. Multivariate Cox proportional hazard models revealed that the DAT uptakes of the anterior, posterior, and whole putamen were significant predictors of the development of LID, whereas DAT activity in the caudate and ventral striatum were not significantly correlated with the development of LID. Additionally, younger age at onset of PD and higher dose of levodopa were also significant predictors of LID. The present results provide convincing evidence that presynaptic dopaminergic denervation plays a crucial role in the development of LID