Dopamine transporter imaging deficit predicts early transition to synucleinopathy in idiopathic rapid eye movement sleep behavior disorder

Objective To determine the usefulness of dopamine transporter (DAT) imaging to identify idiopathic rapid eye movement sleep behavior disorder (IRBD) patients at risk for short‐term development of clinically defined synucleinopathy. Methods Eighty‐seven patients with polysomnography‐confirmed IRBD underwent 123 I‐FP‐CIT DAT‐SPECT. Results were compared to 20 matched controls without RBD who underwent DAT‐SPECT. In patients, FP‐CIT uptake was considered abnormal when values were two standard deviations below controls’ mean uptake. After DAT‐SPECT, patients were followed up during 5.7 ± 2.2 (range, 2.6‐9.9) years. Results Baseline DAT deficit was found in 51 (58.6%) patients. During follow‐up, 25 (28.7%) subjects developed clinically defined synucleinopathy (Parkinson's disease in 11, dementia with Lewy bodies in 13, and multiple system atrophy in 1) with mean latency of 3.2 ± 1.9 years from imaging. Kaplan‐Meier survival analysis showed increased risk of incident synucleinopathy in patients with abnormal DAT‐SPECT than with normal DAT‐SPECT (20% vs 6% at 3 years, 33% vs 18% at 5 years; log rank test, p = 0.006). Receiver operating characteristics curve revealed that reduction of FP‐CIT uptake in putamen greater than 25% discriminated patients with DAT deficit who developed synucleinopathy from patients with DAT deficit that remained disease free after 3 years of follow‐up. At 5‐year follow‐up, DAT‐SPECT had 75% sensitivity, 51% specificity, 44% positive predictive value, 80% negative predictive value, and likelihood ratio 1.54 to predict synucleinopathy. Interpretation DAT‐SPECT identifies IRBD patients at short‐term risk for synucleinopathy. Decreased FP‐CIT putamen uptake greater than 25% predicts synucleinopathy after 3 years’ follow‐up. These observations may be useful to select candidates for disease modification trials in IRBD. Ann Neurol 2017;82:419–428