量化阿尔茨海默病多模态生物标志物关系,提升诊断效率
A Quantitative Analysis of Multimodal Biomarkers in Alzheimer's Disease

- 通过互信息与方差分析,量化各生物标志物间的冗余与预测关系
- 发现tau蛋白沉积与脑萎缩在特定脑区存在强关联,锁定关键区域
- 揭示认知衰退主要由脑萎缩驱动,为精准监测提供依据
尽管多模态方法在阿尔茨海默病(AD)研究中日益普及,旨在整合分子、结构、临床和遗传生物标志物以增强疾病表征,但各模态间的相互关系仍不明确。系统性分析其动态交互对改进疾病建模、识别冗余评估及降低患者负担和采集成本至关重要。本文基于789名来自ADNI数据集的受试者,整合τ-PET、结构磁共振成像(MRI)、认知评分(MMSE和CDR)以及APOE4数据,开展定量分析:(A) 量化跨模态互信息与解释方差,评估冗余与预测依赖性;(B) 分析τ拓扑与结构萎缩在脑区间的关联,筛选出有信息量的感兴趣区(ROIs);(C) 统计分解τ-认知关联中的萎缩相关与独立成分;(D) 识别出与认知衰退高度一致的主导神经退行轨迹。该研究系统刻画了跨模态关系,提升了生物标志物的可解释性与选择能力。代码公开于:https://github.com/antonioscardace/Multimodal-AD。
原文摘要 · Abstract (English)
Despite increasing adoption of multimodal approaches in Alzheimer's Disease (AD) research -- aimed at integrating molecular, structural, clinical, and genetic biomarkers to enhance disease characterization -- the relationships among these modalities remain poorly understood. A systematic analysis of their dynamic interaction is essential for improving disease modeling, identifying redundant assessments, and reducing patient burden and acquisition costs. In this paper, we present a quantitative analysis of multimodal AD biomarkers by integrating tau-PET, structural MRI, cognitive scores (MMSE and CDR), and APOE4 data from 789 subjects drawn from the ADNI dataset. In our analyses, we (A) quantify cross-modal mutual information and explained variance to assess redundancy and predictive dependencies; (B) examine associations between tau topologies and structural atrophy across brain regions to select informative ROIs; (C) perform a statistical decomposition of the tau-cognition association into atrophy-related and atrophy-independent components; (D) and identify a dominant neurodegenerative trajectory that aligns with cognitive decline. This study provides a systematic characterization of cross-modal relationships, improving the interpretability and selection of biomarkers in AD. Code is publicly available at: https://github.com/antonioscardace/Multimodal-AD.
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