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

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.

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.

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.

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.

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.