TEMPO: Transformers for Temporal Disease Progression from Cross-Sectional Data

Electronic Health Record (EHR) prediction models in the intensive care unit must learn from sparse and irregular measurements while preserving the clinical meaning of time and supporting transparent decision-making. We present INTERVenE, a family of Transformer architectures whose input is an interval-based, knowledge-based temporal abstraction (KBTA), a token stream of named clinical concepts (states, trends, events, contexts) drawn from a curated medical ontology, rather than an unnamed bin index or a raw measurement triplet. This naming layer is what we ask KBTA to do: it makes the model's per-token attributions resolve to clinical concepts by construction. INTERVenE offers two complementary variants: an auto-regressive decoder that generates future abstraction trajectories with a per-step risk readout (localizing \emph{when} and \emph{after which events} risk rises), and a bidirectional encoder for single-pass joint risk and time-to-event prediction. Evaluated on 57,078 MIMIC-IV admissions against GRU-D, STraTS, and KarmaLego, INTERVenE-Enc reaches a support-weighted AUPRC$_w$ of 0.672, improving by 0.041 over the strongest neural baseline with non-overlapping 95% bootstrap CIs, while also taking the best AUROC$_w$ (0.901) and length-of-stay MAE (44.4,h). INTERVenE-Ar (AUROC$_w$ $0.854$, AUPRC$_w$ $0.587$ under the same evaluation contract - a strictly harder generative readout) provides a complementary token-level risk trajectory. An input-representation ablation confirms the lift transfers across structured discretizations, positioning KBTA-based intervals as the interpretable substrate that makes per-token attributions resolve to meaningful clinical concepts within the deployed model.

Accurately predicting the temporal evolution of clinical biomarkers is crucial for the early diagnosis and management of neurodegenerative diseases such as Alzheimer's disease. However, this relies on longitudinal data to capture biomarker changes over time, which is often sparse and irregular due to the high cost, labor-intensive nature, and patient burden. To address these challenges, we propose ENC-ODE, an Event-level Neurodegenerative modeling in Continuous time with neural Ordinary Differential Equations. ENC-ODE predicts future biomarker evolution by modeling clinical events through diagnosis-conditioned continuous dynamics. A target-conditioned attention mechanism weights and aggregates event-level predictions for the target time and modality without history compression. Extensive experiments on Alzheimer's Disease Neuroimaging Initiative (ADNI) dataset demonstrate that ENC-ODE outperforms representative sequence models while offering a scalable and neuroscientifically grounded solution for clinical support. The code is available at https://github.com/JardinDelSol/enc-ode.

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.