arXiv:2605.16319cs.LGstat.AP2026-05

用时间锚点和间隙感知注意力预测阿尔茨海默病24个月进展

Forecasting Medium-Horizon Alzheimer's Disease Progression: Residual Gap-Aware Transformers for 24-Month CDR-SB Change from ADNI Clinical and Biomarker Histories

论文配图:Forecasting Medium-Horizon Alzheimer's Disease Progression: Residual Gap-Aware Transformers for 24-Month CDR-SB Change from ADNI Clinical and Biomarker Histories
图 1 · 摘自论文原文
  • 以轻度认知障碍访视为时间锚点,结合临床与生物标志物历史数据
  • 相比基线模型降低13.1%均方误差,相关性提升26.4%
  • 适合关注中长期神经退行性疾病预测的研究者

中长期阿尔茨海默病进展预测困难,因未来临床评分常受基线严重程度影响,而生物标志物数据不规则且观测不全。本文基于统一的阿尔茨海默病神经影像倡议(ADNI)数据表,采用锚点分析法预测24个月的临床痴呆评分总和(CDR-SB)变化。每个标注样本以轻度认知障碍访视为锚点,仅使用该锚点前或当时的临床与生物标志物历史数据,响应变量定义为距24个月最近(18–30个月窗口内)随访时的CDR-SB减去锚点CDR-SB。分析队列包含858名参与者共2,600个锚点样本及7,276条纵向记录。提出一种残差间隙感知变换器模型,融合混合效应统计参考与基于预锚点历史的变换器残差学习。模型引入个体随机截距、观察级三元组标记化处理不规则数据,并在自注意力中加入可学习的非负时间间隙惩罚。在五次参与者级随机分层交叉验证中,该模型在所有指标上均优于基于BIC选择的线性混合效应基线、GRU-D与STraTS,在均方误差上减少13.1%,预测-观测相关性提升26.4%。

原文摘要 · Abstract (English)

Medium-horizon Alzheimer's disease progression prediction is difficult because future clinical scores can remain tied to baseline severity, while biomarker histories are irregular and incompletely observed. We develop an anchor-based analysis of 24-month Clinical Dementia Rating Sum of Boxes (CDR-SB) change using harmonized Alzheimer's Disease Neuroimaging Initiative (ADNI) tables. Each labeled sample is anchored at a mild cognitive impairment visit, uses only clinical and biomarker history observed at or before that anchor, and defines the response as CDR-SB at the future visit closest to 24 months within an 18--30 month window minus anchor CDR-SB. The analytic cohort contains 2,600 labeled anchors from 858 participants and 7,276 longitudinal rows. We propose a residual gap-aware transformer that combines a mixed-effects statistical reference with transformer-based residual learning from pre-anchor clinical and biomarker histories. The model uses participant-level random intercepts in the mixed-effects reference, observation-level triplet tokenization for irregular histories, and a learned nonnegative time-gap penalty inside self-attention. We compare the proposed model with a Bayesian-information-criterion-selected linear mixed-effects baseline, GRU-D, and STraTS under repeated participant-level train--test splits. Across five participant-level random seeds, the proposed model achieves the best mean test performance across all reported metrics, reducing MSE by 13.1% and increasing prediction--observation correlation by 26.4% relative to the mixed-effects baseline. It also improves over both GRU-D and STraTS in mean error and correlation. These results show that statistical anchoring and gap-aware residual learning provide a useful structure for medium-horizon Alzheimer's disease progression prediction.

阿尔茨海默病时间序列注意力机制预测建模

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