The whole-brain structural and functional connectome in Alzheimer’s disease spectrum: A multimodal Bayesian meta-analysis of graph theoretical characteristics

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.