Tracking Prodromal Parkinson´s Disease: A Five-Year Follow-Up of the PARCAS Cohort

Kristína Kulcsárová^1*Petronela Christová¹Martina Bekeová¹Soňa Muránska¹Soňa Mrázová¹Zuzana Mrázová¹Barbora Žecová¹Filip Faglic¹Simona Suváková¹Norbert Leško¹Laura Gombošová²Zuzana Gdovinová¹Matej Škorvánek¹

• ¹Department of Neurology, University of Pavol Jozef Šafárik, Košice, Slovakia
• ²2nd Department of Internal Medicine, University of Pavol Jozef Šafárik, Košice, Slovakia

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. CONCLUSIONS: 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.