不依赖数据补全的Transformer模型,提升阿尔茨海默病预测鲁棒性与可信度
Imputation-free transformer learning enables robust Alzheimer's disease prediction and calibrated uncertainty quantification across heterogeneous clinical cohorts

- 用掩码与跨样本注意力建模患者内部与群体间关系,跳过传统补全步骤
- 在3个不同队列中均实现校准良好的预测,且对缺失模态有合理置信度调整
- 适合关注临床部署可靠性、可解释性与不确定性量化的研究者
阿尔茨海默病的精准诊断与病情进展预测受限于真实临床数据的不完整与异质性。传统数据补全方法引入系统性偏差,扭曲特征关系,导致过度自信预测,尤其影响诊断场景。本文提出NITROGEN,一种无需数据补全的Transformer模型,通过掩码注意力和跨样本注意力联合建模患者内特征依赖与患者间关系,实现直接从部分观测数据中进行多模态学习。模型在ADNI(N=7858次扫描)上训练,并在两个独立队列OASIS-3(N=2675次扫描)和AIBL(N=1286次扫描)上评估。在跨队列诊断与认知评分预测任务中,NITROGEN在预测校准性和不确定性量化方面优于树基集成方法,同时保持竞争性判别性能。跨队列与跨方法分析揭示颞极皮层厚度、年龄和APOE基因型是重要但非充分的分类特征。我们进一步引入模态感知不确定性调节机制,使预测置信度随缺失模态的重要性成比例增加,实现在信息缺失时的合理信心表达。结果表明,无补全注意力学习在队列迁移下仍保持有效区分能力,且在分布差异更大的队列中表现出预期性能下降;强调评估模型时需兼顾校准性、可解释性与跨队列可靠性,而不仅看准确率。
原文摘要 · Abstract (English)
Accurate diagnostic classification and disease-severity prediction for Alzheimer's disease are hampered by the incompleteness and heterogeneity of real-world clinical data. Left unaddressed, these barriers prevent reliable disease modelling and hinder effective clinical evaluation. Conventional imputation strategies introduce systematic bias, distort inter-feature relationships, and yield overconfident predictions, limitations especially consequential in diagnostic settings. Here, we propose NITROGEN, an imputation-free transformer that jointly models within-patient feature dependencies and between-patient relational structure through masked and intersample attention, enabling robust multimodal learning directly from partially observed records. We trained NITROGEN on ADNI (N=7858 scans), and evaluated it on two independent cohorts: OASIS-3 (N=2675 scans) and AIBL (N=1286 scans). Across cohorts and diagnostic and cognitive score prediction tasks, NITROGEN showed robust calibration and uncertainty quantification advantages over tree-based ensemble methods, while maintaining competitive discriminative performance. Cross-cohort and cross-method analyses identified cortical thickness in the temporal pole, age, and APOE genotype as important, though not individually sufficient, features for AD classification. We further introduced a modality-aware uncertainty adjustment that augments predictive uncertainty proportionally to the importance of absent modalities, enabling calibrated confidence when diagnostic information is unavailable. Together, our results show that imputation-free attention learning preserved meaningful discrimination under cohort shift, revealing expected degradation on more distributionally different cohorts, and demonstrate that evaluating models along calibration, interpretability, and cross-cohort reliability, not accuracy alone, is essential for clinical deployment.
Thank you to arXiv for use of its open access interoperability. PaperDance 不是 arXiv 官方产品;中文卡片由大模型生成,请以原文为准。