Diagnostic classification of mild cognitive impairment in Parkinson's disease using subject-level stratified machine-learning analysis.

Background: The timely identification of mild cognitive impairment (MCI) in Parkinson's disease (PD) is essential for early intervention and clinical management, yet it remains a challenge in practice. Methods: We conducted an analysis of 3,154 clinical visits from 896 participants in the Parkinson'...

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Published in:Frontiers in Aging Neuroscience pp. 1 - 21
Main Authors: Wang, Jing, Chen, Yanfang, Xie, Xiao, Wang, Pengwei, Hu, Hang, Han, Hongfang, Wang, Lihan, Zhang, Li
Format: research tables/charts Journal Article
Published: Frontiers Media S.A. 2025
Online Access:View this record in EBSCOhost
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      jtl: Frontiers in Aging Neuroscience
      issn: 16634365
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      dt: 2025
      pid: 40038
      pub: Frontiers Media S.A.
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        189104466
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        10.3389/fnagi.2025.1687925
        189104466
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        atl: Diagnostic classification of mild cognitive impairment in Parkinson's disease using subject-level stratified machine-learning analysis.
      aug:
        au:
          Wang, Jing
          Chen, Yanfang
          Xie, Xiao
          Wang, Pengwei
          Hu, Hang
          Han, Hongfang
          Wang, Lihan
          Zhang, Li
        affil: School of Computer and Information Technology, Xinyang Normal University, Xinyang, China
      sug:
        subj:
          Mild Cognitive Impairment Diagnosis
          Parkinson Disease Complications
          Machine Learning Utilization
          Diagnosis, Computer Assisted
          Prediction Models Evaluation
          Diagnosis, Neurologic
          Health Personnel
          Early Diagnosis
          Patient Care
          Decision Making, Clinical
          Sensitivity and Specificity Evaluation
          Human
          Funding Source
          Male
          Female
          Prospective Studies
          Disease Duration
          Cognition
          Adult
          Middle Age
          Aged
          Logistic Regression
          Youden's J Statistic
          ROC Curve
          Pearson's Correlation Coefficient
          Mann-Whitney U Test
          Chi Square Test
          Descriptive Statistics
          Data Analysis Software
          Reproducibility of Results
          Random Forest
          Age Factors
          Educational Status
          Geriatric Depression Scale
          Scales
          Correlational Studies
          Depression
          Validation Studies
          Clinical Assessment Tools
          Neuropsychological Tests
          Adult: 19-44 years
          Middle Aged: 45-64 years
          Aged: 65+ years
          Male
          Female
      ab: Background: The timely identification of mild cognitive impairment (MCI) in Parkinson's disease (PD) is essential for early intervention and clinical management, yet it remains a challenge in practice. Methods: We conducted an analysis of 3,154 clinical visits from 896 participants in the Parkinson's Progression Markers Initiative (PPMI) cohort. Participants were divided into two groups: cognitively normal (PD-NC, MoCA ≥ 26) and MCI (PD-MCI, 21 ≤ MoCA ≤ 25). To ensure no visit-level information leakage, subject-level stratified sampling was employed to split the data into training (70%) and hold-out test (30%) sets. From an initial set of 12 routinely assessed clinical features, seven were selected using least absolute shrinkage and selection operator (LASSO) logistic regression: age, sex, years of education, disease duration, UPDRS-I, UPDRS-III, and Geriatric Depression Scale (GDS). Four machine learning models—logistic regression (LR), support vector machine (SVM), random forest (RF), and extreme gradient boosting (XGBoost)—were trained using subject-level stratified 10-fold cross-validation with Bayesian optimization. Probabilistic outputs were dichotomized using three thresholding strategies: default 0.5, F1-score maximization, and Youden index maximization. Results: On the independent test set, SVM achieved the highest overall performance with AUC-ROC of 0.7252 and AUC-PR of 0.5008. LR also performed competitively despite its simplicity. RF achieved the top performance in sensitivity, reaching 0.8150. Feature importance analysis consistently highlighted age, years of education, and disease duration as the most informative predictors for distinguishing PD-MCI. Additionally, more stringent site-level split validation yielded slightly decreased overall performance, with LR showing improved AUC-PR. Importantly, the core feature importance ranking remained largely consistent across validation strategies. Conclusion: This study developed and validated robust machine learning models for PD-MCI classification using standard clinical assessments alone. Through subject-level or site-level stratified cross-validation combined with Bayesian optimization, we achieved rigorous model evaluation while minimizing overfitting risk. These findings demonstrate the potential for implementing data-driven, interpretable diagnostic tools to enhance early cognitive impairment screening in routine PD care.
      pubtype: Academic Journal
      doctype:
        research
        tables/charts
        Journal Article
      ougenre: Article
    language: English
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