Longitudinal Trajectory of Dopamine and Serotonin Transporters in Parkinson Disease

Abstract

Parkinson disease (PD) is a multisystem disorder marked by progressive dopaminergic neuronal degeneration in the substantia nigra, as well as nondopaminergic systems. Our aim was to investigate longitudinal changes in N-(3-[¹⁸F]fluoropropyl-2β-carbomethoxy-3β-(4-iodophenyl)nortropane (¹⁸F-FP-CIT) binding at the putamen, substantia nigra, and raphe nuclei in PD. Methods: This retrospective cohort study enrolled 127 patients with PD, who underwent ¹⁸F-FP-CIT PET scans twice or more, and 71 age- and sex-matched healthy controls. A temporal trajectory model was created to estimate the longitudinal trajectories of ¹⁸F-FP-CIT PET specific binding ratios (SBRs) of the putamen, substantia nigra, and raphe nuclei from the prodromal to advanced stages. Associations between SBRs and age and motor severity were evaluated. Results: At baseline, the PD group showed significantly lower ¹⁸F-FP-CIT SBR of the putamen and substantia nigra and higher ¹⁸F-FP-CIT SBR of the median raphe than did the control group. Longitudinally, ¹⁸F-FP-CIT decline of the putamen and substantia nigra began 11.3 and 3.4 y, respectively, before clinical onset on the more affected side. ¹⁸F-FP-CIT decline of the raphe nuclei remained constant for up to 20 y of disease duration. Topographically, ¹⁸F-FP-CIT SBR of the substantia nigra progressed from the caudal and anterolateral to the rostral and posteromedial regions. Conclusion: These results provide in vivo evidence of decreased striatal synaptic dopamine transporter availability approximately 8 y before decreased nigral neuronal dopamine transporter availability, which is strongly correlated with motor deficit. Serotonin transporter availability in the raphe nuclei was elevated in and remained largely unchanged during the disease span.