Predictive markers for early conversion of iRBD to neurodegenerative synucleinopathy diseases

Objective: To determine the predictive value of clinical assessment and dopamine transporter (DAT) uptake for the early development of neurodegenerative synucleinopathy diseases from idiopathic REM sleep behavior disorder (iRBD) over 5 years in a Chinese population. Methods: Forty-three patients with iRBD were administered clinical assessment tests, and 35 were examined by DAT-SPECT imaging during 2011. Cox proportional hazard and Kaplan-Meier analyses were used to evaluate the predictive value of the markers in a follow-up study over 5 years. Results: Eighteen patients (41.9%) developed neurodegenerative synucleinopathy diseases after a median of 4.1 years of prospective follow-up (median interval of 10.5 years from the estimated onset of iRBD symptoms). Patients with higher scores on the Nonmotor Symptom Questionnaire (hazard ratio [HR] 3.11, 95% confidence interval [CI] 1.15-8.40, p = 0.026) and Scale for Outcomes in Parkinson Disease-Autonomic questionnaire (HR 4.46, 95% CI 1.64-12.10, p = 0.003) were more likely to develop neurodegenerative synucleinopathy diseases. Furthermore, the population with decreased Tc-99m-TRODAT-1 binding in the left striatum (HR 2.7, 95% CI 1.02-7.14, p = 0.046) and putamen (HR 3.23, 95% CI 1.16-8.33, p = 0.024) had a relatively higher risk of developing neurodegenerative synucleinopathy diseases. Conclusions: Our findings elucidate the predictive value of autonomic dysfunction and DAT uptake in identifying patients with iRBD at a high risk of progressing into neurodegenerative synucleinopathy diseases and could form a basis for future disease-prevention trials.