Tracking prodromal Parkinson’s disease: a five-year follow-up of the PARCAS cohort

Background The updated International Parkinson and Movement Disorders Society (MDS) research criteria for prodromal Parkinson’s disease (pPD) enable pPD probability assessment. In the PARkinson’s disease associated Colonic Alpha-Synuclein biomarker (PARCAS) study, we previously identified 12 possible (7.5%) and 10 probable (6.3%) pPD cases among 160 elderly individuals undergoing colonoscopy at baseline. Objective To apply MDS pPD criteria in the PARCAS cohort at five-year follow-up (FU), evaluating pPD detection, longitudinal stability, and conversion rates to Parkinson’s disease (PD) or other neurodegenerative diseases. Methods We assessed all risk and prodromal markers except genetic testing; DaTscan and polysomnography (PSG)-confirmed idiopathic REM sleep behavior disorder (iRBD) were available only in a subset of participants. Criteria accuracy was retrospectively evaluated in phenoconverters. Results Among 87/160 participants completing FU, 3 possible (3.5%) and 6 probable (7%) pPD cases were detected. Most remained stable in pPD classification (73 negative, 2 possible, 2 probable pPD), while 4 regressed and 5 progressed in their risk category. Two patients converted to PD and one to corticobasal syndrome (CBS). Baseline sensitivity was 0% at 80% probable pPD threshold (rising to 66% at 50% possible pPD threshold) and reached 100% at 80% threshold at FU. Conclusion pPD probability showed high agreement between baseline and FU assessments. However, absence of key specific markers (PSG-confirmed iRBD and DaTscan) limited baseline sensitivity, which improved only near phenoconversion as additional prodromal symptoms accumulated. Identification of a prodromal CBS case illustrates the potential for detection of atypical parkinsonisms, even with non-α-synuclein pathology, suggesting limited specificity for PD.