用常规就诊数据重建和预测阿尔茨海默病进展轨迹,无需昂贵检查。
Reconstructing and forecasting disease trajectories of patients with Alzheimer's disease using routine data in resource-constrained settings

- 提出GNOVA框架,结合循环神经网络与神经微分方程实现双向预测。
- 在1727名患者上达成CDR-SB误差1.35、MMSE误差2.28,无需影像或生物标志物。
- 可对缺失数据插值、未来状态外推,并给出可靠置信度,适合资源有限地区使用。
阿尔茨海默病是一种进展各异的神经退行性疾病。现有研究多关注未来认知状态预测,较少关注从既往就诊记录重建疾病轨迹。同时,预测不确定性量化常依赖昂贵的影像(MRI、PET)和脑脊液检测,限制了其在资源匮乏环境的应用。本文目标包括:第一,基于不规则就诊数据双向预测认知评分,完整还原疾病进程;第二,实现任意时间点的插值与外推,辅助临床决策;第三,提供校准良好的不确定性估计;第四,仅使用常规就诊数据完成上述任务。提出统一框架GNOVA:GRU-神经微分方程变分自编码器。该模型通过GRU编码器处理任意数量、任意时间点的输入,神经微分方程解码器实现连续状态估计,支持插值与外推,变分自编码器结构生成预测不确定性。基于ADNI数据集1727名患者10年随访数据,模型在未使用任何神经影像或生物标志物的情况下,对CDR-SB和MMSE评分分别达到1.35和2.28的平均绝对误差。特征消融分析表明,年龄、体重指数(BMI)和APOE4状态是关键预测因子。该框架可重构不完整病史并预判未来认知状态。
原文摘要 · Abstract (English)
Alzheimer's disease is a progressive neurodegenerative disorder, and its progression varies substantially across patients. Existing work aims to forecast patients' future cognitive state, with minimal focus on reconstructing the state from past visits. Furthermore, in current research, quantifying predictive uncertainty remains underexplored and relies on costly modalities such as MRI, PET, and CSF, limiting their deployment in resource-limited settings. In this research, our primary objectives are: First, bidirectional prediction of cognitive scores from irregular visits to present the complete disease trajectory. Second, to enable interpolation and extrapolation capabilities to assist clinicians in informed prognostic decision making, and third, to provide a well-calibrated uncertainty estimate for all predictions, and finally, to achieve the objectives using the modalities available during routine visits. We propose a unified framework, GNOVA: A GRU-Neural ODE Variational Autoencoder. The architecture combines a Gated Recurrent Unit encoder and a Neural ODE decoder within a variational autoencoder framework. In our work, we forecast the CDR-SB and MMSE Scores. The GRU encoder allows for any number of inputs at any time point. The Neural-ODE decoder performs continuous estimation, allowing interpolation and extrapolation at any desired time point. The Variational autoencoder allows for uncertainty estimation in predictions. We worked with 1,727 patients from the ADNI dataset over 10 years; the model achieved mean absolute errors of 1.35 and 2.28 for CDR-SB and MMSE scores, respectively, without requiring any neuroimaging or biomarker data. Feature-ablation studies revealed that age, BMI, and APOE4 status were strong predictors. The proposed framework enables the reconstruction of incomplete patient histories and the anticipation of future cognitive states.
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