Non-motor symptoms as critical predictors of quality of life in Parkinson's disease: a machine learning approach.

BACKGROUND: Parkinson's disease (PD) considerably impacts health-related quality of life (HRQoL) through motor and non-motor symptoms. The Parkinson's Disease Questionnaire-39 (PDQ-39) is the most widely used tool to assess HRQoL, encompassing eight dimensions and a Summary Index providing an overall score. Despite advances in machine learning (ML) for predicting disease symptoms and progression, its application to predict HRQoL across these dimensions remains underexplored. METHODS: This study uses complete-case data for 478 of 861 patients from PRISM, a cross-sectional observational survey conducted in six European countries in 2018-2019. Participants were adults with PD recruited through advocacy groups and clinical centers who completed online assessments, providing data on demographics, medication, comorbidities, and disease characteristics (Tolosa et al., 2021). ML models were trained to predict PDQ-39 dimensions and Summary Index scores (0-100; higher = worse HRQoL). Features were preselected using the Boruta algorithm on the training data. Model selection was based on the lowest mean RMSE from 100 bootstrap resamples on the training set. Selected models were then retrained using 1000 bootstrap resamples for robust performance estimation. Final performance was evaluated on a held-out 20% validation set using R², MAE, and RMSE. Feature importance was assessed using permutation importance with MAE loss (100 permutations) on the held-out validation set. Factor Analysis of Mixed Data (FAMD) was used to explore patterns between non-motor symptoms and PDQ-39. RESULTS: Selected models: xgbTree (Summary Index; Activities of Daily Living) and gaussprPoly (all other PDQ-39 dimensions). On the validation set, Summary Index/ Cognitions showed the strongest performance with R² = 0.56/0.53, MAE = 9.60/12.39, RMSE = 12.66/16.20. Permutation feature importance ranked the Non-Motor Symptoms Questionnaire score (sum of 30 non-motor symptoms, range 0-30) as the most important predictor across all models. FAMD showed clustering of Social Support, Bodily Discomfort, and Stigma dimensions with Anxiety. CONCLUSIONS: Our findings demonstrate the critical role of non-motor symptoms in predicting HRQoL in patients with PD. While ML models effectively predict overall HRQoL and cognitive aspects, achieving comparable performance on other dimensions may require additional variables to reduce error. These insights emphasize comprehensive treatment strategies addressing both motor and non-motor symptoms.