Explainable Graph-theoretical Machine Learning with Application to Alzheimer's Disease Prediction

Narmina Baghirova; Duy-Thanh Vũ; Duy-Cat Can; Christelle Schneuwly Diaz; Julien Bodlet; Guillaume Blanc; Georgi Hrusanov; Bernard Ries; Oliver Y. Chén

arXiv · 2503.16286

Explainable Graph-theoretical Machine Learning with Application to Alzheimer's Disease Prediction

Narmina Baghirova·Duy-Thanh Vũ·Duy-Cat Can·Christelle Schneuwly Diaz·Julien Bodlet·Guillaume Blanc·Georgi Hrusanov·Bernard Ries·Oliver Y. Chén

View original source ↗Read source document ↗Export metadata ↓

Abstract

Dementia affects over 55 million people worldwide, projected to reach 139 million by 2050, with Alzheimer's disease (AD) accounting for 60-70% of cases. AD is associated with disruptions in metabolic brain connectivity. Detecting these disruptions early is crucial for AD management. FDG-PET is a useful tool for identifying such impairments. However, most studies rely on group-level analyses or thresholding, potentially masking individual differences and overlooking weaker yet biologically critical brain connections. Moreover, AD prediction largely focuses on univariate rather than multivariate outcomes. To address this, we introduce explainable graph-theoretical machine learning (XGML), a framework for constructing individual metabolic brain graphs and identifying subgraphs most predictive of multivariate disease-related outcomes. Using Alzheimer's Disease Neuroimaging Initiative (ADNI) FDG-PET data, we compared six graph representations against three non-graph baselines, each with six machine learning models using repeated stratified 3-fold cross-validation (10 repeats). The best configuration combined kernel density estimation with Hellinger distance and random forest. Across eight cognitive scores, it reached an overall Fisher-z-averaged Pearson correlation of r=0.595, with strongest performance for ADAS13 (r=0.67), ADAS11 (r=0.65), and ADASQ4 (r=0.62). We identified key edges that were jointly but differentially predictive across outcomes, suggesting their potential as network biomarkers of cognitive decline. Preliminary external feasibility validation on an OASIS3 cohort yielded weak predictive performance for CDRSB (r=0.26) and MMSE (r=0.18), likely reflecting cohort, protocol, and diagnostic differences. Overall, our results suggest the promise of graph-theoretical machine learning for biomarker discovery, disease prediction, and understanding the neural mechanisms underlying AD.

Explore related subjects

cs.LG

Keep this discovery

Explore connections, maps & timelines

BibTeX RIS

Narmina Baghirova, Duy-Thanh Vũ, Duy-Cat Can, Christelle Schneuwly Diaz, Julien Bodlet, Guillaume Blanc, Georgi Hrusanov, Bernard Ries, Oliver Y. Chén. 2026-09-16. Explainable Graph-theoretical Machine Learning with Application to Alzheimer's Disease Prediction. https://arxiv.org/abs/2503.16286

Cite the original work for its findings. Save a collection to share your selection of sources.

KEEP EXPLORING

Related papers

arXiv2026

A Probabilistic Approach for Model Alignment with Human Comparisons

A growing trend involves integrating human knowledge into learning frameworks, leveraging subtle human feedback to refine AI models. While these approaches have shown promising results in practice, the theoretical understanding of when and why such approaches are effective remains limited. This work takes steps toward developing a theoretical framework for analyzing the conditions under which human comparisons can enhance the traditional supervised learning process. Specifically, this paper studies the effective use of noisy-labeled data and human comparison data to address challenges arising from noisy environment and high-dimensional models. We propose a two-stage "Supervised Learning+Learning from Human Feedback" (SL+LHF) framework that connects machine learning with human feedback through a probabilistic bisection approach. The two-stage framework first learns low-dimensional representations from noisy-labeled data via an SL procedure and then uses human comparisons to improve the model alignment. To examine the efficacy of the alignment phase, we introduce a concept, termed the "label-noise-to-comparison-accuracy" (LNCA) ratio. This paper identifies from a theoretical perspective the conditions under which the "SL+LHF" framework outperforms the pure SL approach; we then leverage this LNCA ratio to highlight the advantage of incorporating human evaluators in reducing sample complexity. We validate the framework on a real high-dimensional crowdfunding-prediction task: under a fixed query budget, trading labels for comparisons improves accuracy precisely when labels are scarce, and the findings hold when the evaluator is replaced by real large language models. A study conducted via Amazon Mechanical Turk (MTurk) further validates the model primitives.

cs.LG↗

arXiv2026

An Initial Introduction to Cooperative Multi-Agent Reinforcement Learning

Multi-agent reinforcement learning (MARL) has exploded in popularity in recent years. While numerous approaches have been developed, they can be broadly categorized into three main types: centralized training and execution (CTE), centralized training for decentralized execution (CTDE), and decentralized training and execution (DTE). CTE methods assume centralization during training and execution (e.g., with fast, free, and perfect communication) and have the most information during execution. CTDE methods are the most common, as they leverage centralized information during training while enabling decentralized execution -- using only information available to that agent during execution. Decentralized training and execution methods make the fewest assumptions and are often simple to implement. This text is an introduction to cooperative MARL -- MARL in which all agents share a single, joint reward. It is meant to explain the setting, basic concepts, and common methods for the CTE, CTDE, and DTE settings. It does not cover all work in cooperative MARL as the area is quite extensive. I have included work that I believe is important for understanding the main concepts in the area and apologize to those that I have omitted. Topics include simple applications of single-agent methods to CTE as well as some more scalable methods that exploit the multi-agent structure, independent Q-learning and policy gradient methods and their extensions, as well as value function factorization methods including the well-known VDN, QMIX, and QPLEX approaches, and centralized critic methods including MADDPG, COMA, and MAPPO. I also discuss common misconceptions, the relationship between different approaches, and some open questions.

cs.LG↗

arXiv2026

Transductive Off-policy Proximal Policy Optimization

Proximal Policy Optimization (PPO) is a popular model-free reinforcement learning algorithm, esteemed for its simplicity and efficacy. However, due to its inherent on-policy nature, its proficiency in harnessing data from disparate policies is constrained. This paper introduces a novel off-policy extension to the original PPO method, christened Transductive Off-policy PPO (ToPPO). Herein, we provide theoretical justification for incorporating off-policy data in PPO training and prudent guidelines for its safe application. Our contribution includes a novel formulation of the policy improvement lower bound for prospective policies derived from off-policy data, accompanied by a computationally efficient mechanism to optimize this bound, underpinned by assurances of monotonic improvement. Comprehensive experimental results across six representative tasks underscore ToPPO's promising performance.

cs.LG↗