用物理启发的神经模型,精准预测阿尔茨海默病认知衰退轨迹。
Physics-Informed Neural Koopman Machine for Interpretable Longitudinal Personalized Alzheimer's Disease Forecasting

- 基于动力系统与注意力机制,融合多模态数据建模
- 同时预测多个认知指标,准确率优于传统方法
- 可解释性强,识别关键脑区和生物标志物贡献
阿尔茨海默病(AD)早期个体认知衰退的预测对疾病评估与管理至关重要。现有方法难以在保持可解释性的同时,整合多模态数据进行纵向个性化预测。为此,我们提出神经库普曼机(NKM),一种受动力系统与注意力机制启发的新型机器学习架构,能够利用遗传、神经影像、蛋白质组学及人口统计学等多模态数据,同步预测多个认知评分。NKM融合解析知识(α)与生物学知识(β),引导特征分组并控制分层注意力机制,以提取相关模式。通过在库普曼算子框架中实现融合分组感知的分层注意力,NKM将复杂的非线性轨迹转化为可解释的线性表示。我们在阿尔茨海默病神经影像计划(ADNI)数据集上验证了NKM的有效性。结果表明,NKM在预测认知衰退轨迹方面持续优于传统机器学习与深度学习模型,具体表现为:(1)可同步预测多个认知评分;(2)量化不同生物标志物对特定认知评分的预测贡献;(3)识别最能预测认知恶化的脑区。NKM通过可解释的显式系统,实现了基于历史多模态数据的个性化、可解释的未来认知衰退预测,并揭示了AD进展的潜在多模态生物学基础。
原文摘要 · Abstract (English)
Early forecasting of individual cognitive decline in Alzheimer's disease (AD) is central to disease evaluation and management. Despite advances, it is as of yet challenging for existing methodological frameworks to integrate multimodal data for longitudinal personalized forecasting while maintaining interpretability. To address this gap, we present the Neural Koopman Machine (NKM), a new machine learning architecture inspired by dynamical systems and attention mechanisms, designed to forecast multiple cognitive scores simultaneously using multimodal genetic, neuroimaging, proteomic, and demographic data. NKM integrates analytical ($α$) and biological ($β$) knowledge to guide feature grouping and control the hierarchical attention mechanisms to extract relevant patterns. By implementing Fusion Group-Aware Hierarchical Attention within the Koopman operator framework, NKM transforms complex nonlinear trajectories into interpretable linear representations. To demonstrate NKM's efficacy, we applied it to study the Alzheimer's Disease Neuroimaging Initiative (ADNI) dataset. Our results suggest that NKM consistently outperforms both traditional machine learning methods and deep learning models in forecasting trajectories of cognitive decline. Specifically, NKM (1) forecasts changes of multiple cognitive scores simultaneously, (2) quantifies differential biomarker contributions to predicting distinctive cognitive scores, and (3) identifies brain regions most predictive of cognitive deterioration. Together, NKM advances personalized, interpretable forecasting of future cognitive decline in AD using past multimodal data through an explainable, explicit system and reveals potential multimodal biological underpinnings of AD progression.
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