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Leakage-Controlled Multimodal Learning for Diagnosis and Progression Prediction in Alzheimer's Disease Research

arXiv机器学习 2026-10-09 12:00 7 阅读 查看原文

Alzheimer's disease prediction involves irregular visits, heterogeneous measurements and incomplete modalities.

This study presents a multimodal multitask framework combining an adapted SFCN MRI encoder, four causal clinical Transformers, shared fusion and task-specific ODE-GRU dynamics.

Fine-tuning and LoRA adapt the final two MRI blocks.

Task-DRO balances task losses, while Group-CVaR targets cohort and comorbidity strata.

Branch-specific input controls, subject-grouped partitions and empirical causality checks support longitudinal evaluation.

Across 2,649 subjects and 17,317 visits from ADNI, OASIS-2 and MIRIAD, internal validation yields diagnosis, stage-1 progression and first-stage-1-visit progression AUROCs of 0.935 +/- 0.002, 0.884 +/- 0.003 and 0.870 +/- 0.005, respectively (mean +/- SD across three seeds). Corresponding hybrid AUROCs are 0.951, 0.909 and 0.896.

Next-visit MMSE mean absolute error (MAE) is 1.61 points; worst-stratum diagnosis AUROC is 0.827 +/- 0.008.

Sampled ADNI explanations identify task-specific input dependence.

OASIS-3 external validation yields network and hybrid diagnosis AUROCs of 0.763 and 0.767, hybrid next-visit progression AUROC of 0.764, diagnosis calibration error decreasing from 0.197 to 0.052, and next-visit MMSE MAE of 0.86.

Seed-42 paired ablations of six components yield pooled diagnosis and progression AUROC differences between -0.004 and +0.004; removing clinical encoder inputs lowers diagnosis AUROC by 0.272.

The framework integrates longitudinal prediction, missing-modality handling, auxiliary comorbidity modelling and subgroup evaluation within a common pipeline.