Predicting Cognitive Decline in Parkinson’s Disease Using Artificial Neural Networks: An Explainable AI Approach

Background/Objectives: The study aims to identify key cognitive and non-cognitive\r\nvariables (e.g., clinical, neuroimaging, and genetic data) predicting cognitive decline in\r\nParkinson’s disease (PD) patients using machine learning applied to a sample (N = 618) from the Parkinson’s Progression Markers Initiative database. Traditional research has mainly employed explanatory approaches to explore variable relationships, rather than maximizing predictive accuracy for future cognitive decline. In the present study, we implemented a predictive framework that integrates a broad range of baseline cognitive, clinical, genetic, and imaging data to accurately forecast changes in cognitive functioning in PD patients. Methods: An artificial neural network was trained on baseline data to predict general cognitive status three years later. Model performance was evaluated using 5-fold stratified cross-validation. We investigated model interpretability using explainable artificial intelligence techniques, including Shapley Additive Explanations (SHAP) values, Group-Wise Feature Masking, and Brute-Force Combinatorial Masking, to identify the most influential predictors of cognitive decline. Results: The model achieved a recall of 0.91 for identifying patients who developed cognitive decline, with an overall classification accuracy of 0.79. All applied explainability techniques consistently highlighted baseline MoCA scores, memory performance, the motor examination score (MDS-UPDRS Part III), and anxiety as the most predictive features. Conclusions: From a clinical perspective, the findings can support the early detection of PD patients who are more prone to developing\r\ncognitive decline, thereby helping to prevent cognitive impairments by designing specific treatments. This can improve the quality of life for patients and caregivers, supporting patient autonomy.