Comparative Value of Cognitive and Functional Assessments for Predicting 24-Month Progression from Mild Cognitive Impairment to Alzheimer's Disease: An ADNI Cohort Study

Accurate prediction of progression from mild cognitive impairment (MCI) to Alzheimer's disease (AD) is important for prognosis, patient management, and clinical trial enrollment. Cognitive and functional assessments are routinely used in memory clinics, but their relative predictive value remains unclear. We sought to identify which assessments are most predictive of 24-month progression from MCI to AD. We analyzed 2,430 participants with baseline MCI from the Alzheimer's Disease Neuroimaging Initiative (ADNI) who were classified by 24-month progression to AD. Extreme Gradient Boosting (XGBoost) models were trained using repeated stratified 5-fold cross-validation with 10 repetitions. We compared demographic and genetic variables, global cognitive measures (MMSE, ADAS-Cog13, CDR-SB, MoCA), episodic memory, executive function, functional status, and Everyday Cognition (ECog) questionnaires. The baseline clinical model (age, sex, education, APOE {varepsilon}4 status) achieved an area under the receiver operating characteristic curve (AUC) of 0.692. Episodic memory showed the highest predictive performance (AUC = 0.915), followed by the Functional Activities Questionnaire (AUC = 0.913). Combining episodic memory, functional assessment, and executive function achieved the best performance (AUC = 0.943, sensitivity = 0.857, specificity = 0.889). Among individual memory measures, Logical Memory Delayed Recall achieved the highest standalone performance (AUC = 0.896), whereas RAVLT Learning provided minimal incremental value. Episodic memory demonstrated the strongest predictive performance among the individual assessment domains evaluated of 24-month progression from MCI to AD, with functional assessment providing substantial complementary value. Streamlined assessment batteries emphasizing episodic memory and functional status may improve efficient risk stratification in memory clinics and AD clinical trials.