Jung Hwan Shin1, Jee-Young Lee2, Yu-Kyeong Kim2, Sung-A Shin1, Heejung Kim2, Hyunwoo Nam1, Beomseok Jeon1. 1. From the Department of Neurology (J.H.S., J.-Y.L., H.N.), Seoul Metropolitan Government-Seoul National University Boramae Medical Center and Seoul National University College of Medicine; Department of Nuclear Medicine (Y.-K.K., S.-A.S., H.K.), Seoul Metropolitan Government-Seoul National University Boramae Medical Center; and Department of Neurology (B.J.), Seoul National University Hospital and Seoul National University College of Medicine, South Korea. 2. From the Department of Neurology (J.H.S., J.-Y.L., H.N.), Seoul Metropolitan Government-Seoul National University Boramae Medical Center and Seoul National University College of Medicine; Department of Nuclear Medicine (Y.-K.K., S.-A.S., H.K.), Seoul Metropolitan Government-Seoul National University Boramae Medical Center; and Department of Neurology (B.J.), Seoul National University Hospital and Seoul National University College of Medicine, South Korea. wieber04@snu.ac.kr yk3181@snu.ac.kr.
Abstract
OBJECTIVE: To elucidate longitudinal changes in the dopamine transporter (DAT) availability in association with the prodromal markers in idiopathic REM sleep behavior disorder (iRBD), we analyzed a longitudinal prospective iRBD cohort data. METHOD: The study cohort consisted of patients with iRBD, individuals with Parkinson disease (PD), and healthy controls. All participants were evaluated for olfaction, neuropsychological tests, and 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. RESULT: DAT patterns in patients with iRBD with baseline hyposmia, constipation, and mild parkinsonian signs distributed toward the PD pattern and clearly distinguished from the healthy control pattern. The DAT pattern moved toward the PD pattern over time in some patients with iRBD 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 [95% confidence interval 1.16-21.08]). The combination of hyposmia and baseline PD pattern of DAT predicted 67% of the conversion (hazard ratio 7.89 [confidence interval 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.
OBJECTIVE: To elucidate longitudinal changes in the dopamine transporter (DAT) availability in association with the prodromal markers in idiopathic REM sleep behavior disorder (iRBD), we analyzed a longitudinal prospective iRBD cohort data. METHOD: The study cohort consisted of patients with iRBD, individuals with Parkinson disease (PD), and healthy controls. All participants were evaluated for olfaction, neuropsychological tests, and 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. RESULT: DAT patterns in patients with iRBD with baseline hyposmia, constipation, and mild parkinsonian signs distributed toward the PD pattern and clearly distinguished from the healthy control pattern. The DAT pattern moved toward the PD pattern over time in some patients with iRBD 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 [95% confidence interval 1.16-21.08]). The combination of hyposmia and baseline PD pattern of DAT predicted 67% of the conversion (hazard ratio 7.89 [confidence interval 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.