提出联合进展模型,精准刻画阿尔茨海默病与血管性痴呆混合病理的演化路径。
Joint Progression Modeling (JPM): A Probabilistic Framework for Mixed-Pathology Progression
- 将单一疾病轨迹视为部分排序,构建联合进展的先验概率框架。
- 在合成数据上比强基线模型排序准确率提升21%。
- 适用于研究多种神经退行性疾病共存时的演化规律,适合临床研究者。
事件驱动模型(EBM)从横断面数据推断疾病进展,传统EBM假设个体仅受单一疾病影响。然而,神经退行性疾病中混合病理极为常见。本文提出联合进展模型(JPM),将单病程轨迹视为部分排序,并建立联合进展的先验分布。研究了四种变体(成对比较、Bradley-Terry、Plackett-Luce和Mallows),分析了三个性质:(i) 校准性——模型能量越低,越接近真实排序;(ii) 分离性——采样排序与随机排列的区分度;(iii) 锐度——聚合排序的稳定性。所有变体均校准且分离性接近完美;锐度因变体而异,可由输入部分排序的特征(数量、长度、冲突、重叠)良好预测。合成实验显示,JPM比强基线模型SA-EBM在排序准确率上提升约21%。基于NACC数据,Mallows型JPM与基线模型结果更符合现有文献对阿尔茨海默病与血管性痴呆混合病理进展的认知。
原文摘要 · Abstract (English)
Event-based models (EBMs) infer disease progression from cross-sectional data, and standard EBMs assume a single underlying disease per individual. In contrast, mixed pathologies are common in neurodegeneration. We introduce the Joint Progression Model (JPM), a probabilistic framework that treats single-disease trajectories as partial rankings and builds a prior over joint progressions. We study several JPM variants (Pairwise, Bradley-Terry, Plackett-Luce, and Mallows) and analyze three properties: (i) calibration -- whether lower model energy predicts smaller distance to the ground truth ordering; (ii) separation -- the degree to which sampled rankings are distinguishable from random permutations; and (iii) sharpness -- the stability of sampled aggregate rankings. All variants are calibrated, and all achieve near-perfect separation; sharpness varies by variant and is well-predicted by simple features of the input partial rankings (number and length of rankings, conflict, and overlap). In synthetic experiments, JPM improves ordering accuracy by roughly 21 percent over a strong EBM baseline (SA-EBM) that treats the joint disease as a single condition. Finally, using NACC, we find that the Mallows variant of JPM and the baseline model (SA-EBM) have results that are more consistent with prior literature on the possible disease progression of the mixed pathology of AD and VaD.
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