Objective: To elucidate longitudinal changes in the dopamine transporter (DAT) availability in association with the prodromal markers in idiopathic rapid-eye-movement sleep behavior disorder (iRBD), we analyzed a longitudinal prospective iRBD cohort data.

Method: The study cohort consisted of iRBD, Parkinson’s disease (PD) patients and healthy controls. All participants were evaluated for olfaction, neuropsychological tests, the Movement disorders society-Unified Parkinson’s disease Rating Scale and underwent ¹⁸F-FP-CIT PET scans every 2 years. We calculated the DAT pattern by performing the principal component analysis of tracer uptakes in 6 striatal regions.

Results: DAT patterns in iRBD patients with baseline hyposmia, constipation and mild parkinsonian signs distributed toward PD-pattern and clearly distinguished from the healthy control pattern. The DAT pattern moved toward PD-pattern over time in some iRBD patients during the follow-up and baseline hyposmia was the only biomarker significantly associated with this change. Baseline PD-pattern of DAT predicted 58% of disease converters (Hazard Ratio=4.95 [1.16~21.08]). The combination of hyposmia and baseline PD pattern of DAT predicted 67% of the conversion (Hazard Ratio=7.89 [1.85~33.69]). The estimated sample size required for a simulated neuroprotective clinical trial was 63 per group when the annual change of DAT pattern was used as an outcome in the subgroup with baseline DAT PD-pattern and hyposmia, which is the smallest number reported so far.

Conclusion: Baseline and longitudinal monitoring of the DAT pattern can be a useful biomarker in identifying individuals with a high risk of disease conversion and in selecting the potential population for clinical trials in iRBD.