用多模态数据与有序回归,自动精准评估阿尔茨海默病严重程度。
Multimodal Ordinal Modeling of Alzheimer's Disease Severity Using Structural MRI and Clinical Data
- 融合结构MRI、人口与遗传数据,用注意力机制建模多源信息。
- 有序回归模型在临床分期一致性上表现最佳(QWK 0.549)。
- 模型结果可解释,适合临床辅助决策与疾病进展研究。
阿尔茨海默病(AD)的严重程度评估亟需准确且可扩展的方法,但当前临床分期耗时且易受主观差异影响。本文提出一种基于注意力增强的多模态机器学习框架,结合T1加权MRI、人口统计学和遗传变量,采用有序回归实现自动化、可解释的疾病分期。在来自ADNI、AIBL和NIFD的数据集上,通过分层队列划分进行训练与验证,并构建严格独立测试集(所有训练、验证、预处理及超参数调优均排除测试个体)。单模态中,影像模型邻近阶段准确率达0.963,与临床分期一致性(QWK)为0.444,优于表格模型(QWK 0.433)。多模态融合提升整体性能:非有序基线模型误差最低(MAE 0.340),而有序多模态模型达到最高邻近阶段准确率(0.970)和最强一致性(QWK 0.549)。说明有序建模更契合CDR量表的顺序特性。通过Grad CAM++与SHAP分析验证了模型具有解剖与临床合理性,支持透明决策。该方法为智能辅助临床诊断提供了稳健、可解释且可扩展的解决方案。
原文摘要 · Abstract (English)
Neurodegenerative diseases such as Alzheimer's disease (AD) require accurate and scalable tools for assessing disease severity, yet current clinical staging remains time-intensive and prone to variability. We propose an attention-enhanced multimodal machine learning framework with ordinal regression for automated and interpretable AD severity staging. The framework integrates T1-weighted MRI with demographic and genetic variables and compares unimodal and multimodal architectures using ordinal and non-ordinal prediction heads. Models were trained and validated using cohort-stratified splits derived from the ADNI, AIBL, and NIFD datasets. A strictly held-out test set was constructed using subjects excluded from all training, validation, preprocessing, and hyperparameter tuning procedures, with subject-level splitting employed throughout to prevent data leakage. Among unimodal approaches, the T1-weighted MRI model achieved slightly higher adjacent-stage accuracy (0.963) and agreement with clinical staging (QWK 0.444) than the tabular model (QWK 0.433). Integrating imaging, demographic, and genetic information improved overall performance. The multimodal non-ordinal baseline achieved the lowest prediction error (MAE 0.340), whereas the ordinal multimodal model achieved the highest adjacent-stage accuracy (0.970) and strongest agreement with clinical staging (QWK 0.549). These findings indicate that ordinal formulations better capture the ordered structure of the CDR scale and yield predictions more consistent with clinical staging. Explainability analyses using Grad CAM++ and SHAP demonstrated anatomically and clinically plausible model behavior, supporting transparent decision-making. Overall, attention-based multimodal learning with ordinal regression represents a robust, interpretable, and scalable approach for automated AD severity staging and AI-assisted clinical decision support.
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