Multi-cohort machine learning identifies predictors of cognitive impairment in Parkinson’s disease

Abstract Cognitive impairment is a frequent complication of Parkinson’s disease (PD), affecting up to half of newly diagnosed patients. To improve early detection and risk assessment, we developed machine learning models using clinical data from three independent PD cohorts, which are (LuxPARK, PPMI, ICEBERG). Models were trained to predict mild cognitive impairment ( PD-MCI ) and subjective cognitive decline ( SCD ) using Explainable Artificial Intelligence (XAI) for classification and time-to-event analysis. Multi-cohort models showed greater performance stability over single-cohort models, while retaining competitive average performance. Age at diagnosis and visuospatial ability were identified as key predictors. Significant sex differences observed highlight the importance of considering sex-specific factors in cognitive assessment. Men were more likely to report SCD . Our findings highlight the potential of multi-cohort machine learning for early identification and personalized management of cognitive decline in PD.