# Dual Model Deep Learning for Alzheimer Prognostication

arXiv: https://arxiv.org/abs/2512.19099 · HTML: https://mlsanity.com/paper/2512.19099/

## Key facts

- No citing papers in the map yet (data through 14 Oct 2026).
- Builds on 12 of its 65 references that are in the map.
- First posted on arXiv 22 Dec 2025.

## Builds on (most cited first, 12 of 12)

- [PyTorch: An Imperative Style, High-Performance Deep Learning Library](https://mlsanity.com/paper/1912.01703/) (2019)
- [Dropout as a Bayesian Approximation: Representing Model Uncertainty in Deep Learning](https://mlsanity.com/paper/1506.02142/) (2015)
- [Gaussian Error Linear Units (GELUs)](https://mlsanity.com/paper/1606.08415/) (2016)
- [What Uncertainties Do We Need in Bayesian Deep Learning for Computer Vision?](https://mlsanity.com/paper/1703.04977/) (2017)
- [Recurrent Neural Networks for Multivariate Time Series with Missing Values](https://mlsanity.com/paper/1606.01865/) (2016)
- [DeepSurv: Personalized Treatment Recommender System Using A Cox Proportional Hazards Deep Neural Network](https://mlsanity.com/paper/1606.00931/) (2016)
- [RETAIN: An Interpretable Predictive Model for Healthcare using Reverse Time Attention Mechanism](https://mlsanity.com/paper/1608.05745/) (2016)
- [The role of explainability in creating trustworthy artificial intelligence for health care: a comprehensive survey of the terminology, design choices, and evaluation strategies](https://mlsanity.com/paper/2007.15911/) (2020)
- [Deep Learning for Survival Analysis: A Review](https://mlsanity.com/paper/2305.14961/) (2023)
- [Deep Representation Learning of Patient Data from Electronic Health Records (EHR): A Systematic Review](https://mlsanity.com/paper/2010.02809/) (2020)
- [Multimodal Machine Learning in Image-Based and Clinical Biomedicine: Survey and Prospects](https://mlsanity.com/paper/2311.02332/) (2023)
- [Transformer Model for Alzheimer's Disease Progression Prediction Using Longitudinal Visit Sequences](https://mlsanity.com/paper/2507.03899/) (2025)

## Abstract (arXiv)

Disease modifying therapies for Alzheimer's disease demand precise timing decisions, yet current predictive models require longitudinal observations and provide no uncertainty quantification, rendering them impractical at the critical first visit when treatment decisions must be made. We developed PROGRESS (PRognostic Generalization from REsting Static Signatures), a dual-model deep learning framework that transforms a single baseline cerebrospinal fluid biomarker assessment into actionable prognostic estimates without requiring prior clinical history. The framework addresses two complementary clinical questions: a probabilistic trajectory network predicts individualized cognitive decline with calibrated uncertainty bounds achieving near-nominal coverage, enabling honest prognostic communication; and a deep survival model estimates time to conversion from mild cognitive impairment to dementia. Using data from over 3,000 participants across 43 Alzheimer's Disease Research Centers in the National Alzheimer's Coordinating Center database, PROGRESS substantially outperforms Cox proportional hazards, Random Survival Forests, and gradient boosting methods for survival prediction. Risk stratification identifies patient groups with seven-fold differences in conversion rates, enabling clinically meaningful treatment prioritization. Leave-one-center-out validation demonstrates robust generalizability, with survival discrimination remaining strong across held-out sites despite heterogeneous measurement conditions spanning four decades of assay technologies. By combining superior survival prediction with trustworthy trajectory uncertainty quantification, PROGRESS bridges the gap between biomarker measurement and personalized clinical decision-making.