arXiv:2606.24604cs.AI2026-06

用深度学习预测阿尔茨海默病进展,还能给出可靠度和未来轨迹。

Uncertainty-Aware Longitudinal Forecasting of Alzheimer's Disease Progression Using Deep Learning

论文配图:Uncertainty-Aware Longitudinal Forecasting of Alzheimer's Disease Progression Using Deep Learning
图 1 · 摘自论文原文
  • 构建概率框架,同时预测病情阶段、未来轨迹和不确定性。
  • 在ADNI数据集上,对轻度痴呆与痴呆的区分准确率显著提升。
  • 可分离随机与认知不确定性,适合临床决策和罕见进展分析。

纵向建模阿尔茨海默病进展需不仅预测最可能的下一步诊断,还需描述患者未来演变路径及预测可靠性。现有深度学习方法多简化为单步分类,将正常、轻度认知障碍(MCI)、痴呆视为平级类别,难以揭示不确定性随时间累积机制。本文提出一种概率框架,结合有序诊断预测、多时域轨迹生成与分解不确定性估计。采用时序融合变换器编码器,搭配CORAL有序输出层、非对称损失权重与转换器过采样,尊重疾病阶段顺序并增强对MCI向痴呆转化的敏感性。基于学习的患者上下文表示,自回归混合密度网络生成五年期诊断状态、CDR总分、MMSE定向力与海马体积的概率轨迹。在ADNI数据集上,模型优于线性、循环与变压器基线,在下一访问诊断预测中表现最佳,尤其在区分MCI与痴呆上优势明显。生成轨迹实现近名义90%可信区间覆盖,不确定性随预测时长扩大,生物标志物动态符合预期阿尔茨海默病进展。进一步通过解析混合方差与五成员自助集成,分离随机不确定性与认知不确定性,前者提供最强编码器多样性,后者在稀有进展模式、MCI与痴呆患者中更高,且在外部数据集OASIS-3上随预测误差上升。

原文摘要 · Abstract (English)

Longitudinal modelling of Alzheimer's disease progression is clinically useful only if it can describe not just the most likely next diagnosis, but how a patient may evolve over time and how reliable that forecast is. Most deep learning approaches reduce this problem to single-step classification, treating cognitively normal, mild cognitive impairment, and dementia as flat categories while providing limited insight into how uncertainty accumulates across future visits. We propose a probabilistic framework that combines ordinal diagnosis prediction, multi-horizon trajectory generation, and decomposed uncertainty estimation. A Temporal Fusion Transformer encoder is adapted with a CORAL ordinal output layer, asymmetric loss weighting, and converter oversampling to respect disease-stage ordering and improve sensitivity to MCI-to-dementia transitions. Conditioned on the learned patient-context representation, an autoregressive Mixture Density Network generates five-year probabilistic trajectories for diagnosis state, CDR Sum of Boxes, MMSE orientation, and hippocampal volume. On ADNI, the model outperforms linear, recurrent, and transformer baselines for next-visit diagnosis prediction, with the strongest gains on MCI-versus-dementia discrimination. Generated trajectories achieve near-nominal 90% credible interval coverage, widening uncertainty across the forecast horizon, and biomarker dynamics consistent with expected Alzheimer's disease progression. We further separate aleatoric from epistemic uncertainty using analytic mixture variance and a five-member bootstrap ensemble, which provides the strongest encoder diversity and output-level epistemic signal. Epistemic uncertainty is higher for rare progression archetypes, MCI and dementia patients, and under external evaluation on OASIS-3, where it increases alongside prediction error.

阿尔茨海默病长期预测不确定性轨迹生成

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