Development and Validation of a Machine Learning Model for Dementia Staging in a Heterogeneous Cognitive Impairment...

With the emergence of disease-modifying therapies, precise staging of dementia is urgent. This study aimed to develop a machine learning model integrating multimodal data to achieve objective staging of dementia severity in patients with cognitive impairment.

A total of 149 patients (100 with Alzheimer's disease) were recruited. Demographic data, neuropsychological scores, and multimodal PET features were collected. Subjects were randomly split (7:3) into training and validation cohorts. PET features were screened using Boruta and LASSO to generate composite SUVR scores, while key demographic and neuropsychological predictors were identified through univariate and multivariate logistic regression analyses. Seven machine learning algorithms (logistic regression, decision tree, random forest, XGBoost, LightGBM, support vector machine, and artificial neural network) were trained using grid search and fivefold cross-validation. Model performance was assessed using the area under the receiver operating characteristic curve (AUC), calibration plots, and decision curve analysis (DCA), with SHAP analysis employed for interpretability.

The cohort comprised 80 very mild-to-mild (CDR 0.5-1) and 69 moderate-to-severe (CDR 2-3) dementia cases. Key predictors included years of education, MMSE, and composite amyloid and FDG SUVR scores. The XGBoost model demonstrated robust performance, achieving an AUC of 0.888 (95% CI: 0.777-0.967) in the independent validation cohort. SHAP analysis identified MMSE and composite FDG SUVR scores as the most significant contributors to disease staging.

This study constructed and internally validated an interpretable multimodal model for dementia severity staging. While the results are promising, the developed web-based tool currently serves as a proof-of-concept to demonstrate how such models could potentially assist in optimizing patient management and screening candidates for novel therapies, pending further external validation.