构建个性化认知衰退数字孪生模型,融合多模态数据与不确定性分析。
Toward Personalized Digital Twins for Cognitive Decline Assessment: A Multimodal, Uncertainty-Aware Framework

- 基于隐状态空间模型建模个体化时间动态
- 多模态融合使五年内ADAS13等指标预测误差最低
- 适合临床研究与个性化治疗规划者使用
认知衰退在个体间高度异质,影响预后评估、试验设计和治疗规划。本文提出个性化认知衰退评估数字孪生(PCD-DT),一种多模态且具备不确定性感知能力的框架,用于从稀疏、噪声大且不规则的纵向数据中建模患者特异性疾病轨迹。该框架包含三个组件:(1) 隐状态空间模型实现个体化时间动态建模,(2) 多模态融合整合临床、生物标志物与影像特征,(3) 不确定性感知验证与自适应更新机制以增强数字孪生鲁棒性。此外,我们探讨了条件生成模型在数据增强与罕见进展模式压力测试中的应用。初步可行性研究基于TADPOLE纵向数据,显示正常与阿尔茨海默病群体在五年内ADAS13、脑室体积和海马体积上具有明显分离。在3,003个就诊对序列上,采用LSTM的多模态预测实验表明,结合认知与MRI的配置在ADAS13(标准化RMSE=0.4419)和脑室体积(标准化RMSE=0.5842)上表现最优,优于最后一次观测值继承基线。还讨论了高维影像融合的贝叶斯张量建模方法。结果支持该架构的可行性,同时指出需加强不确定性校准与长时序预测评估。PCD-DT为神经退行性疾病个性化体外建模提供了原则性起点,是迈向临床可部署、不确定性感知数字孪生系统的基石。
原文摘要 · Abstract (English)
Cognitive decline is highly heterogeneous across individuals, which complicates prognosis, trial design, and treatment planning. We present the Personalized Cognitive Decline Assessment Digital Twin (PCD-DT), a multimodal and uncertainty-aware framework for modeling patient-specific disease trajectories from sparse, noisy, and irregular longitudinal data. The framework combines three methodological components: (1) latent state-space models for individualized temporal dynamics, (2) multimodal fusion for clinical, biomarker, and imaging features, and (3) uncertainty-aware validation and adaptive updating for robust digital twin operation. We also outline how conditional generative models can support data augmentation and stress testing for underrepresented progression patterns. As a preliminary feasibility study, we analyze longitudinal TADPOLE trajectories and show clear separation between cognitively normal and Alzheimer's disease cohorts in ADAS13, ventricle volume, and hippocampal volume over five years. We further conduct a multimodal next-visit prediction ablation using an LSTM sequence model on 3{,}003 visit-pair sequences derived from TADPOLE, where the combined cognitive plus MRI configuration achieves the lowest standardized RMSE for both ADAS13 (0.4419) and ventricle volume (0.5842), outperforming a Last Observation Carried Forward baseline. A Bayesian tensor modeling component for high-dimensional imaging fusion is also discussed. These results support the feasibility of the proposed architecture while also highlighting the need for stronger uncertainty calibration and longer-horizon predictive evaluation. The PCD-DT framework provides a principled starting point for personalized in silico modeling in neurodegenerative disease. This work positions PCD-DT as a foundational step toward clinically deployable, uncertainty-aware digital twin systems.
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