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Reconstructing and forecasting disease trajectories of patients with Alzheimer's disease using routine data in resource-constrained settings

This study introduces GNOVA, a GRU-Neural ODE Variational Autoencoder, for bidirectional prediction of cognitive scores (CDR-SB and MMSE) in Alzheimer's disease using only routine clinical data, without MRI, PET, or CSF. The model achieves MAEs of 1.35 and 2.28 on the ADNI dataset, and feature ablation highlights age, BMI, and APOE4 as strong predictors. The framework enables reconstruction of incomplete patient histories and anticipation of future cognitive states.

SourcearXiv AIAuthor: Ratnadeep Das, Atri Chatterjee, Sitikantha Roy

[2606.07798] Reconstructing and forecasting disease trajectories of patients with Alzheimer's disease using routine data in resource-constrained settings

[Submitted on 5 Jun 2026]

Title:Reconstructing and forecasting disease trajectories of patients with Alzheimer's disease using routine data in resource-constrained settings

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Abstract:Alzheimer's disease is a progressive neurodegenerative disorder, and its progression varies substantially across patients. Existing work aims to forecast patients' future cognitive state, with minimal focus on reconstructing the state from past visits. Furthermore, in current research, quantifying predictive uncertainty remains underexplored and relies on costly modalities such as MRI, PET, and CSF, limiting their deployment in resource-limited settings. In this research, our primary objectives are: First, bidirectional prediction of cognitive scores from irregular visits to present the complete disease trajectory. Second, to enable interpolation and extrapolation capabilities to assist clinicians in informed prognostic decision making, and third, to provide a well-calibrated uncertainty estimate for all predictions, and finally, to achieve the objectives using the modalities available during routine visits. We propose a unified framework, GNOVA: A GRU-Neural ODE Variational Autoencoder. The architecture combines a Gated Recurrent Unit encoder and a Neural ODE decoder within a variational autoencoder framework. In our work, we forecast the CDR-SB and MMSE Scores. The GRU encoder allows for any number of inputs at any time point. The Neural-ODE decoder performs continuous estimation, allowing interpolation and extrapolation at any desired time point. The Variational autoencoder allows for uncertainty estimation in predictions. We worked with 1,727 patients from the ADNI dataset over 10 years; the model achieved mean absolute errors of 1.35 and 2.28 for CDR-SB and MMSE scores, respectively, without requiring any neuroimaging or biomarker data. Feature-ablation studies revealed that age, BMI, and APOE4 status were strong predictors. The proposed framework enables the reconstruction of incomplete patient histories and the anticipation of future cognitive states.

Subjects:

Artificial Intelligence (cs.AI); Machine Learning (cs.LG); Neurons and Cognition (q-bio.NC)

Cite as: arXiv:2606.07798 [cs.AI]

(or arXiv:2606.07798v1 [cs.AI] for this version)

https://doi.org/10.48550/arXiv.2606.07798

arXiv-issued DOI via DataCite (pending registration)

Submission history

From: Ratnadeep Das [view email] [v1] Fri, 5 Jun 2026 19:23:56 UTC (1,205 KB)

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