Comprehensive Methodology for Sample Augmentation in EEG Biomarker Studies for Alzheimers Risk Classification

Background: Dementia, characterized by progressive cognitive decline, is a major global health challenge. Alzheimer's disease (AD) is the predominant type, accounting for approximately 70% of dementia cases worldwide. Electroencephalography (EEG)-derived measures have shown potential in identifying AD risk, but obtaining sufficiently large samples for reliable comparisons remains a challenge. Objective: This study implements a comprehensive methodology that integrates signal processing, data harmonization, and statistical techniques to increase sample size and improve the reliability of Alzheimer's disease risk classification models. Methods: We used a multi-step approach combining advanced EEG preprocessing, feature extraction, harmonization techniques, and propensity score matching (PSM) to optimize the balance between healthy non-carriers (HC) and asymptomatic E280A mutation Alzheimer's disease carriers (ACr). Data were harmonized across four databases, adjusting for site effects while preserving important covariate effects such as age and sex. PSM was applied at different ratios (2:1, 5:1, and 10:1) to explore the impact of sample size differences on model performance. The final dataset was subjected to machine learning analysis using decision trees, with cross-validation to ensure robust model performance.