Aims: This study aimed to characterize convergent biochemical and cardiovascular imaging endophenotypes of atherosclerotic risk in early PD and to implement an interpretable machine-learning architecture integrating multimodal clinical and imaging parameters for precision cardiovascular risk profiling and cardiometabolic classification.
Methods: A total of 125 early-stage idiopathic PD patients and age- and sex-matched controls were analyzed. Feature space was reduced using cross-validated Least Absolute Shrinkage and Selection Operator (LASSO) with penalty tuning and stability selection to mitigate multicollinearity. XGBoost, Random Forest, RBF-kernel Support Vector Machine, and Stochastic Gradient Boosting models were trained under a train–hold-out framework with Bayesian hyperparameter optimization. Model performance was assessed via bootstrapping, and interpretability was provided using SHapley Additive exPlanations (SHAP).
Results: PD patients showed increased hypertension (54.4%; OR 3.2, p=0.007) and hypercholesterolemia (OR 2.8, p=0.01), with excess left ventricular systolic dysfunction (28.8% vs 0%, p<0.001), aortic insufficiency (20.0% vs 0%, p=0.001), and high-risk carotid plaques (unstable 40.8% vs 2.0%; calcified 49.6% vs 18.0%; both p<0.001). Inflammation was elevated (CRP 7.70±7.22 vs 3.34±1.31 mg/L, p<0.001) with reduced lymphocyte-to-monocyte ratio (LMR) (3.99±1.94 vs 5.13±1.45, p<0.001). XGBoost achieved superior discrimination (accuracy 0.941, 95% CI 0.911–0.971; sensitivity 0.923; specificity 0.889; PPV 0.960, 95% CI 0.930–0.990; AUC 0.95, 95% CI 0.91–0.983; Brier 0.07), with explainability dominated by LMR (SHAP 100%), followed by CRP (92.6%) and glucose-metabolic markers (65.6%).
Conclusion: PD demonstrates a convergent inflammatory–metabolic endophenotype with elevated carotid and cardiac risk burden. An explainable XGBoost-based multimodal framework implicated LMR and C-RP as discriminative biomarkers for targeted surveillance in early PD.
Accelerated atherosclerosis carotid plaque vulnerability lymphocyte-to-monocyte ratio machine learning risk stratification Parkinson's disease XGBoost algorithm
The study was conducted in accordance with the Declaration of Helsinki, and approved by the Institutional Ethics Committee of Ankara Etlik City Hospital (AEŞH-BADEK2024-331). Informed Consent Statement: Written informed consent was obtained from all subjects involved in the study.
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| Primary Language | English |
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| Subjects | Computational Neuroscience, Central Nervous System |
| Journal Section | Research Article |
| Authors | |
| Submission Date | February 4, 2026 |
| Acceptance Date | February 28, 2026 |
| Publication Date | March 27, 2026 |
| IZ | https://izlik.org/JA93BG98HZ |
| Published in Issue | Year 2026 Volume: 7 Issue: 2 |
TR DİZİN ULAKBİM and International Indexes (1d)
Interuniversity Board (UAK) Equivalency: Article published in Ulakbim TR Index journal [10 POINTS], and Article published in other (excuding 1a, b, c) international indexed journal (1d) [5 POINTS]
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