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

Background: Dementia, marked by cognitive decline, is a global health challenge. Alzheimer's disease (AD), the leading type, accounts for ~70% of cases. Electroencephalography (EEG) measures show promise in identifying AD risk, but obtaining large samples for reliable comparisons is challenging. Objective: This study integrates signal processing, harmonization, and statistical techniques to enhance sample size and improve AD risk classification reliability. Methods: We used advanced EEG preprocessing, feature extraction, harmonization, and propensity score matching (PSM) to balance healthy non-carriers (HC) and asymptomatic E280A mutation carriers (ACr). Data from four databases were harmonized to adjust site effects while preserving covariates like age and sex. PSM ratios (2:1, 5:1, 10:1) were applied to assess sample size impact on model performance. The final dataset underwent machine learning analysis with decision trees and cross-validation for robust results. Results: Balancing sample sizes via PSM significantly improved classification accuracy, ranging from 0.92 to 0.96 across ratios. This approach enabled precise risk identification even with limited samples. Conclusion: Integrating data processing, harmonization, and balancing techniques improves AD risk classification accuracy, offering potential for other neurodegenerative diseases.

FAST functional connectivity implicates P300 connectivity in working memory deficits in Alzheimer's disease

Measuring transient functional connectivity is an important challenge in Electroencephalogram (EEG) research. Here, the rich potential for insightful, discriminative information of brain activity offered by high temporal resolution is confounded by the inherent noise of the medium and the spurious nature of correlations computed over short temporal windows. We propose a novel methodology to overcome these problems called Filter Average Short-Term (FAST) functional connectivity. First, long-term, stable, functional connectivity is averaged across an entire study cohort for a given pair of Visual Short Term Memory (VSTM) tasks. The resulting average connectivity matrix, containing information on the strongest general connections for the tasks, is used as a filter to analyse the transient high temporal resolution functional connectivity of individual subjects. In simulations, we show that this method accurately discriminates differences in noisy Event-Related Potentials (ERPs) between two conditions where standard connectivity and other comparable methods fail. We then apply this to analyse activity related to visual short-term memory binding deficits in two cohorts of familial and sporadic Alzheimer's disease. Reproducible significant differences were found in the binding task with no significant difference in the shape task in the P300 ERP range. This allows new sensitive measurements of transient functional connectivity, which can be implemented to obtain results of clinical significance.