Clinical and dopaminergic imaging characteristics of the "FARPRESTO" cohort of trial-ready idiopathic REM sleep behavior patients

Introduction: Idiopathic/isolated REM Sleep Behavior disorder (iRBD) is considered the prodromal stage of alpha-synucleinopathies. Thus, iRBD patients are the ideal target for disease-modifying therapy. The risk FActoRs PREdictive of phenoconversion in iRBD Italian STudy (FARPRESTO) is an ongoing Italian database aimed at identifying risk factors of phenoconversion, and eventually to ease clinical trial enrollment of well characterized subjects. Methods: Polysomnography-confirmed iRBD patients were retrospectively and prospectively enrolled. Baseline harmonized clinical and nigro-striatal functioning data were collected at baseline. Nigro-striatal functioning was evaluated by dopamine transporter (DaT) SPECT and categorized with visual semi-quantification. Longitudinal data were evaluated to assess phenoconversion. Cox regressions were applied to calculate Hazard Ratios. Results: 365 patients were enrolled, and 289 patients with follow-up (67.7±7.3 yo, 237 males, mean follow-up 40±37 months) were included in this study. At follow-up, 97 iRBD patients (33.6%) phenoconverted to an overt synucleinopathy. Older age, motor and cognitive impairment, constipation, urinary and sexual disfunction, depression, and visual semi-quantification of nigro-striatal functioning predicted phenoconversion. The remaining 268 patients are in follow-up within the FARPRESTO project. Conclusion: Clinical data (older age, motor and cognitive impairment, constipation, urinary and sexual disfunction, depression) predicted phenoconversion in this multicenter longitudinal observational study. A standardized visual approach for semi-quantification of DaT-SPECT is proposed as practical risk factor for phenoconversion in iRBD patients. To note, non-converted and newly diagnosed iRBD patients, who represent a trial-ready cohort for upcoming disease-modification trials, are currently being enrolled and followed in the FARPRESTO study. New data are expected to allow better risk characterization.