# Learning the irreversible progression trajectory of Alzheimer's disease

arXiv: https://arxiv.org/abs/2403.06087 · HTML: https://mlsanity.com/paper/2403.06087/

## Key facts

- Cited by 2 papers in the map (data through 14 Oct 2026).
- Builds on 10 of its 26 references that are in the map.
- First posted on arXiv 10 Mar 2024.

## Builds on (most cited first, 10 of 10)

- [XGBoost: A Scalable Tree Boosting System](https://mlsanity.com/paper/1603.02754/) (2016)
- [Revisiting Deep Learning Models for Tabular Data](https://mlsanity.com/paper/2106.11959/) (2021)
- [Tabular Data: Deep Learning is Not All You Need](https://mlsanity.com/paper/2106.03253/) (2021)
- [Right for the Right Reasons: Training Differentiable Models by Constraining their Explanations](https://mlsanity.com/paper/1703.03717/) (2017)
- [Interpretations are useful: penalizing explanations to align neural networks with prior knowledge](https://mlsanity.com/paper/1909.13584/) (2019)
- [Convolutional Neural Networks for Classification of Alzheimer's Disease: Overview and Reproducible Evaluation](https://mlsanity.com/paper/1904.07773/) (2019)
- [Proper Network Interpretability Helps Adversarial Robustness in Classification](https://mlsanity.com/paper/2006.14748/) (2020)
- [Self-Interpretable Model with TransformationEquivariant Interpretation](https://mlsanity.com/paper/2111.04927/) (2021)
- [Longitudinal Pooling & Consistency Regularization to Model Disease Progression from MRIs](https://mlsanity.com/paper/2003.13958/) (2020)
- [XADLiME: eXplainable Alzheimer's Disease Likelihood Map Estimation via Clinically-guided Prototype Learning](https://mlsanity.com/paper/2207.13223/) (2022)

## Built on by (most cited first, 2 of 2)

- [Temporally Detailed Hypergraph Neural ODEs for Disease Progression Modeling](https://mlsanity.com/paper/2510.17211/) (2025)
- [Longitudinal Bayesian Learning of Continuous Disease Position across the Alzheimer's Disease Continuum](https://mlsanity.com/paper/2608.19436/) (2026)

## Abstract (arXiv)

Alzheimer's disease (AD) is a progressive and irreversible brain disorder that unfolds over the course of 30 years. Therefore, it is critical to capture the disease progression in an early stage such that intervention can be applied before the onset of symptoms. Machine learning (ML) models have been shown effective in predicting the onset of AD. Yet for subjects with follow-up visits, existing techniques for AD classification only aim for accurate group assignment, where the monotonically increasing risk across follow-up visits is usually ignored. Resulted fluctuating risk scores across visits violate the irreversibility of AD, hampering the trustworthiness of models and also providing little value to understanding the disease progression. To address this issue, we propose a novel regularization approach to predict AD longitudinally. Our technique aims to maintain the expected monotonicity of increasing disease risk during progression while preserving expressiveness. Specifically, we introduce a monotonicity constraint that encourages the model to predict disease risk in a consistent and ordered manner across follow-up visits. We evaluate our method using the longitudinal structural MRI and amyloid-PET imaging data from the Alzheimer's Disease Neuroimaging Initiative (ADNI). Our model outperforms existing techniques in capturing the progressiveness of disease risk, and at the same time preserves prediction accuracy.