Liu Wenxiong, Zuo Chao, Chen Li, Lan Huan, Luo Chunyan, Li Xiao, Kemp Graham J, Lui Su, Suo Xueling, Gong Qiyong
Department of Radiology, Huaxi MR Research Center (HMRRC), Institution of Radiology and Medical Imaging, West China Hospital of Sichuan University, Chengdu, Sichuan 610041, China; Functional and Molecular Imaging Key Laboratory of Sichuan Province, West China Hospital of Sichuan University, Chengdu, Sichuan 610041, China; Research Unit of Psychoradiology, Chinese Academy of Medical Sciences, Chengdu 610041, China; Department of Interventional Therapy, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China.
Department of Radiology, Huaxi MR Research Center (HMRRC), Institution of Radiology and Medical Imaging, West China Hospital of Sichuan University, Chengdu, Sichuan 610041, China; Functional and Molecular Imaging Key Laboratory of Sichuan Province, West China Hospital of Sichuan University, Chengdu, Sichuan 610041, China; Research Unit of Psychoradiology, Chinese Academy of Medical Sciences, Chengdu 610041, China.
Neurosci Biobehav Rev. 2025 Jul;174:106174. doi: 10.1016/j.neubiorev.2025.106174. Epub 2025 Apr 24.
Alzheimer's disease (AD) spectrum is increasingly recognized as a progressive network-disconnection syndrome. Neuroimaging studies using graph theoretical analysis (GTA) have reported alterations in the topological properties of whole-brain structural and functional connectomes in both preclinical AD and AD patients, though findings remain inconsistent. This study aimed to identify robust changes in multimodal GTA metrics across the AD spectrum through a comprehensive literature search and Bayesian random-effects meta-analyses. The analysis included 53 studies (37 functional and 17 structural), involving 1649 AD patients, 1455 preclinical AD patients, and 1771 healthy controls (HC). Results revealed lower structural network integration (evidenced by higher characteristic path length and/or normalized characteristic path length) and segregation (evidenced by lower clustering coefficient and local efficiency) in AD and preclinical AD patients compared to HC. Functional network segregation was also lower in AD patients, while preclinical AD showed preserved functional topology despite structural changes. Moderator analyses identified potential methodological moderators, including neuroimaging technique, node and edge definitions, and network type, although further validation is needed. These findings support the progressive disconnection hypothesis in the AD spectrum and suggest that structural network alterations may precede functional network changes. Furthermore, the results help clarify inconsistencies in previous studies and highlight the utility of graph-based metrics as biomarkers for staging AD progression.
阿尔茨海默病（AD）谱系越来越被认为是一种进行性网络连接障碍综合征。使用图论分析（GTA）的神经影像学研究报告了临床前AD和AD患者全脑结构和功能连接组拓扑特性的改变，尽管研究结果仍不一致。本研究旨在通过全面的文献检索和贝叶斯随机效应荟萃分析，确定AD谱系中多模态GTA指标的稳健变化。该分析包括53项研究（37项功能研究和17项结构研究），涉及1649例AD患者、1455例临床前AD患者和1771例健康对照（HC）。结果显示，与HC相比，AD和临床前AD患者的结构网络整合度较低（以较高的特征路径长度和/或标准化特征路径长度为证据），分离度较低（以较低的聚类系数和局部效率为证据）。AD患者的功能网络分离度也较低，而临床前AD尽管结构发生了变化，但功能拓扑结构保持不变。调节因素分析确定了潜在的方法学调节因素，包括神经影像学技术、节点和边的定义以及网络类型，尽管还需要进一步验证。这些发现支持了AD谱系中的进行性连接障碍假说，并表明结构网络改变可能先于功能网络改变。此外，研究结果有助于澄清先前研究中的不一致之处，并突出基于图的指标作为AD进展分期生物标志物的效用。
