A Neurosymbolic Approach for Explainable Early Diagnosis of Alzheimer's Disease

Alzheimer's disease (AD) progression is often described through the amyloid-tau-neurodegeneration, or AT(N), cascade. However, most longitudinal models represent this cascade either as a fixed sequence of biomarkers or as a black-box forecasting task. This makes it difficult to determine when biologically guided biomarker relationships influence future regional pathology. In this study, we introduce Bayesian Networks with Latent Time Embedding (BN-LTE), a Bayesian structural framework for stage-aware modeling of AD progression. BN-LTE estimates disease pseudotime from baseline biomarker profiles and constrains directed dependencies according to biologically plausible AT(N) ordering. Posterior spline-varying structural equations are then used to link initial multimodal measurements with future annualized regional tau-PET change. Across repeated subject-disjoint evaluations using ADNI data, BN-LTE shows strong spatial reconstruction of tau progression compared with the included forecasting baselines. Beyond spatial reconstruction, BN-LTE recovers posterior stage-varying AT(N)-constrained effects and identifies a mid-pseudotime window of amyloid sensitivity. This window is supported by model-implied g-formula contrasts, root-adjusted AIPW, mechanism-sensitive ablations, and robustness analyses across spline and prior specifications. Overall, these findings position BN-LTE as a Bayesian structural framework for forecasting tau progression while examining stage-dependent AT(N)-cascade mechanisms in observational longitudinal neuroimaging data. Our code is available at https://github.com/danleneurocom/BN-LTE.

Acoustic biomarkers show promise for detecting Alzheimer's Disease (AD), yet whether the cues driving diagnostic AI align with those salient to human listeners is underexplored across languages and genders, where pathological markers and perceptual strategies differ. We train models to predict clinical AD status (pathology) and human perceptual scores across Mandarin and Greek, male and female speakers. Using SHAP for interpretability and statistical models for validation, we compare feature importance by subgroup. Results reveal a context-dependent divergence: pathological-perceptual alignment is significant for Mandarin and female speakers but disappears for Greek and male speakers, where pathology models did not exceed chance; this is a failure mode that population-specific auditing surfaces. Global Explainable AI (XAI) explanations can mask critical demographic divergences, highlighting the need for population-specific explainability auditing for equitable deployment of clinical speech AI.

Speech-based automatic detection of Alzheimer's disease (AD) provides a non-invasive and scalable approach to early cognitive screening. AD affects both lexical-semantic organization and speech production, including atypical pauses and word elongations. However, existing methods have yet to fully integrate these paralinguistic cues with linguistic content. We propose LLM-Anchored Paralinguistic Enrichment (LAPE), which enriches LLM-derived linguistic representations with paralinguistic cues through three coordinated innovations. The first is prosodic event textualization, which enables the LLM to model pauses and elongations jointly with lexical content by encoding them as explicit markers with bounded duration-aware repetition. The second is lexico-prosodic unitization and chunking, which preserves event identity and magnitude in both modalities by pooling only consecutive word units. The third is text-anchored paralinguistic fusion, which integrates local and utterance-level speech features by using NormGate to normalize and dynamically scale them relative to text. We evaluate LAPE on ADReSS and ADReSSo using participant-level cross-validation and leave-one-subject-out evaluation. LAPE achieves state-of-the-art performance across all four primary settings. Code will be released upon acceptance.