Abstract
INTRODUCTION: Parkinson's disease (PD) is the second most common neurodegenerative disorder. The risk of frailty is significantly higher in patients with PD than in age-matched individuals without PD. This study aimed to develop a machine learning-based predictive model for frailty in PD. METHODS: We conducted a cross-sectional study of early- and middle-stage PD patients recruited from June 2024 to June 2025 at Shenzhen People's Hospital. Frailty was assessed using the Fried criteria (five components: gait speed, grip strength, physical activity, fatigue, and weight loss). A total of 42 demographic and clinical variables, including disease history, Montreal cognitive assessment (MoCA), and unified Parkinson's disease rating scale (MDS-UPDRS) scores, were collected and compared between PD patients with and without frailty. Spearman correlation and LASSO regression were used to identify independent risk factors. Multiple machine learning algorithms were applied to construct predictive models. Model performance was evaluated using receiver operating characteristic (ROC) curves, area under the ROC curve (AUC), decision curve analysis (DCA), calibration plots, and forest plots. RESULTS: A total of 205 PD patients were enrolled (133 non-frail, 72 frail; mean age non-frail 62.92 ± 9.69 years, frail 68.13 ± 8.44 years). Significant group differences were found in sex (p = 0.013), age (p < 0.001), disease severity (MDS-UPDRS, p < 0.001; modified Hoehn-Yahr stage (H&Y stage), p < 0.001), alcohol consumption (p = 0.010), MoCA (p < 0.001), HAMD (p = 0.001), and Hamilton anxiety rating scale (HAMA) (p < 0.001). Eight features were identified as independent predictors of frailty: sex, age, alcohol use, Modified H&Y stage, UPDRS-IV score, HAMA score, executive function, and naming. Among all tested algorithms, logistic regression achieved the best predictive performance (AUC = 0.83 in the test set), outperforming other machine learning models. CONCLUSION: Frailty in PD was associated with female sex, older age, alcohol use, and more advanced disease severity. Patients with PD and frailty exhibited higher MDS-UPDRS scores, more severe cognitive impairment, and greater levels of depression and anxiety. Integrating clinical data with machine learning, especially logistic regression, provides a reliable and scalable tool for early identification and risk stratification of frailty in PD.