Interpretable AI for neural signal decoding in dementia: an EEG ensemble approach to differential diagnosis

Abstract

The differential diagnosis between Alzheimer’s disease (AD) and frontotemporal dementia (FTD) presents a significant clinical challenge due to overlapping early-stage symptom profiles. Conventional resting-state EEG provides limited sensitivity to the impaired neural plasticity and lateralized cortical degeneration frequently observed in FTD. We developed a domain-informed heterogeneous ensemble framework incorporating dynamic neural reactivity and hemispheric asymmetry metrics from 19-channel EEG recordings acquired from 88 participants (36 AD, 23 FTD, 29 cognitively normal controls) during resting-state and photic stimulation paradigms. A neural reactivity vector (V_diff) was derived to quantify state-dependent spectral transitions. The 1,014-dimensional feature space was reduced to 200 features via recursive feature elimination, prioritizing spectral power distributions, hemispheric asymmetry indices (HAI), and stimulation-induced reactivity parameters. A weighted ensemble of Extreme Gradient Boosting (XGBoost) and Random Forest classifiers was evaluated using a subject-aware 90/10 holdout split with internal five-fold cross-validation. The optimized model achieved a multi-class segment-level accuracy of 95.63% on an independently held-out test partition of 1,281 segments, with an internal five-fold cross-validation mean of 0.9846 ± 0.003. FTD-specific precision reached 0.9907. SHAP analysis identified beta-band hemispheric asymmetry and alpha-band reactivity as the principal contributors to class separation. These findings indicate that the integration of dynamic state-transition measures with structural asymmetry proxies enhances electrophysiological discrimination between dementia subtypes. The framework provides a computationally efficient and biologically interpretable alternative to deep learning–based methodologies for EEG-driven dementia classification.