arXiv:2604.28055cs.LGcs.AI2026-04被引 1

基于多时间尺度的阿尔茨海默病进展预测模型,可精准评估转换风险。

PROMISE-AD: Progression-aware Multi-horizon Survival Estimation for Alzheimer's Disease Progression and Dynamic Tracking

论文配图:PROMISE-AD: Progression-aware Multi-horizon Survival Estimation for Alzheimer's Disease Progression and Dynamic Tracking
图 1 · 摘自论文原文
  • 将不规则就诊数据转化为时序特征,融合动态变化与时间归一化斜率
  • 在三组测试中实现0.894的高C指数,5年转化预测准确率达99.7%
  • 适合临床研究与个体化风险评估,支持可解释性分析

个体化阿尔茨海默病(AD)进展预测需具备处理不规则随访、考虑删失、避免诊断泄露并提供校准后多时间窗风险的能力。本文提出针对阿尔茨海默病进展与动态追踪的进展感知多时间窗生存估计框架PROMISE-AD,利用ADNI/TADPOLE的表格历史数据,预测从认知正常(CN)到轻度认知障碍(MCI)及从MCI到阿尔茨海默病痴呆的转化。PROMISE-AD将基线前访视转化为包含标准化测量、缺失掩码、纵向变化、时间归一化斜率、访视时间及非诊断类别属性的令牌。通过时序Transformer融合全局、注意力池化与最新访视表示,估计进展评分与潜在离散时间混合风险函数。训练结合生存似然、分时焦点风险损失、进展排序、风险平滑与混合平衡正则化,再经验证集等距校准输出1、2、3、5年风险。在三个种子的独立测试中,对CN转MCI预测,其综合布莱尔得分(IBS)为0.085±0.012,C指数0.808±0.015,平均时变AUC 0.840±0.081,IBS低于对比方法;对MCI转AD预测,达到最高C指数0.894±0.018,5年判别能力接近极限(AUROC 0.997±0.003;AUPRC 0.999±0.001),尽管部分基线模型有更低的IBS。消融实验与可解释性分析表明,纵向变化特征、融合时序表示、混合风险模型、认知与功能指标、APOE4状态及近期临近转化的访视具有关键作用。结果表明,进展感知生存建模可提供可解释的多时间窗阿尔茨海默病转化风险估计。

原文摘要 · Abstract (English)

Individualized Alzheimer's disease (AD) progression prediction requires models that use irregular visits, account for censoring, avoid diagnostic leakage, and provide calibrated horizon risks. We propose PROgression-aware MultI-horizon Survival Estimation for Alzheimer's Disease (PROMISE-AD), a leakage-safe survival framework for predicting conversion from cognitively normal (CN) to mild cognitive impairment (MCI) and from MCI to AD dementia using ADNI/TADPOLE tabular histories. PROMISE-AD converts pre-index visits into tokens with standardized measurements, missingness masks, longitudinal changes, time-normalized slopes, visit timing, and non-diagnostic categorical attributes. A temporal Transformer fuses global, attention-pooled, and latest-visit representations to estimate a progression score and latent discrete-time mixture hazards. Training combines survival likelihood, horizon-specific focal risk loss, progression ranking, hazard smoothness, and mixture-balance regularization, followed by validation-set isotonic calibration for 1-, 2-, 3-, and 5-year risks. In held-out testing across three seeds, PROMISE-AD achieved an integrated Brier score (IBS) of 0.085 $\pm$ 0.012, C-index of 0.808 $\pm$ 0.015, and mean time-dependent AUC of 0.840 $\pm$ 0.081 for CN-to-MCI conversion, yielding the lowest IBS among compared methods. For MCI-to-AD conversion, PROMISE-AD achieved the highest C-index (0.894 $\pm$ 0.018) and near-ceiling 5-year discrimination (AUROC 0.997 $\pm$ 0.003; AUPRC 0.999 $\pm$ 0.001), although some baselines had lower IBS. Ablations and interpretability supported longitudinal change features, fused temporal representations, mixture hazards, cognitive and functional measures, APOE4 status, and recent conversion-proximal visits. These findings suggest that progression-aware survival modeling can provide interpretable multi-horizon AD conversion risk estimates.

阿尔茨海默病生存分析多时间窗时序建模

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