Task-Related EEG as a Biomarker for Preclinical Alzheimer's Disease: An Explainable Deep Learning Approach.

The early detection of Alzheimer's disease (AD) in cognitively healthy individuals remains a major preclinical challenge. EEG is a promising tool that has shown effectiveness in detecting AD risk. Task-related EEG has been rarely used in Alzheimer's disease research, as most studies have focused on resting-state EEG. An interpretable deep learning framework-Interpretable Convolutional Neural Network (InterpretableCNN)-was utilized to identify AD-related EEG features. EEG data were recorded during three cognitive task conditions, and samples were labeled based on APOE genotype and polygenic risk scores. A 100-fold leave-p%-subjects-out cross-validation (LPSO-CV) was used to evaluate model performance and generalizability. The model achieved an ROC AUC of 60.84% across the tasks and subjects, with a Kappa value of 0.22, indicating fair agreement. Interpretation revealed a consistent focus on theta and alpha activity in the parietal and temporal regions-areas commonly associated with AD pathology. Task-related EEG combined with interpretable deep learning can reveal early AD risk signatures in healthy individuals. InterpretableCNN enhances transparency in feature identification, offering a valuable tool for preclinical screening.