Development and validation of a combined clinical and MRI-based biomarker model to differentiate mild cognitive impairment from mild Alzheimer's disease

Abstract

Background: Two of the most common complaints seen in neurology clinics are Alzheimer's disease (AD) and mild cognitive impairment (MCI), characterized by similar symptoms. The aim of this study was to develop and internally validate the diagnostic value of combined neurological and radiological predictors in differentiating mild AD from MCI as the outcome variable, which helps in preventing AD development. Methods: A cross-sectional study of 161 participants was conducted in a general healthcare setting, including 30 controls, 71 mild AD, and 60 MCI. Binary logistic regression was used to identify predictors of interest, with collinearity assessment conducted prior to model development. Model performance was assessed through calibration, shrinkage, and decision-curve analyses. Finally, the combined clinical and radiological model was compared to models utilizing only clinical or radiological predictors. Results: The final model included age, sex, education status, Montreal cognitive assessment, Global Cerebral Atrophy Index, Medial Temporal Atrophy Scale, mean hippocampal volume, and Posterior Parietal Atrophy Index, with the area under the curve of 0.978 (0.934–0.996). Internal validation methods did not show substantial reduction in diagnostic performance. Combined model showed higher diagnostic performance compared to clinical and radiological models alone. Decision curve analysis highlighted the usefulness of this model for differentiation across all probability levels. Conclusion: A combined clinical-radiological model has excellent diagnostic performance in differentiating mild AD from MCI. Notably, the model leveraged straightforward neuroimaging markers, which are relatively simple to measure and interpret, suggesting that they could be integrated into practical, formula-driven diagnostic workflows without requiring computationally intensive deep learning models.