Diffusion MRI-based analysis of structural connectivity and its association with cognitive decline in alzheimer’s disease
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- Alzheimer’s disease is increasingly recognized as a disorder affecting large-scale brain networks rather than isolated brain regions. The objective of this study was to investigate structural connectivity alterations associated with disease progression and cognitive decline using diffusion magnetic resonance imaging (dMRI) and tractography. Whole-brain structural connectomes were reconstructed from participants classified as cognitively normal (CN), mild cognitive impairment (MCI), or dementia. Global connectivity, network-specific connectivity within the default mode, salience, and central executive networks, associations between individual structural connections and cognitive performance, and graph-theoretical metrics were analyzed. Global connectivity showed only modest differences across diagnostic groups. At the network level, significant alterations were observed within the salience network, whereas no significant group effects were detected in the default mode or central executive networks. Edge-wise analyses identified several structural connections associated with cognitive performance, particularly involving parietal, occipital, temporal, and limbic regions. Furthermore, graph-theoretical analyses revealed reduced node strength, clustering coefficient, and closeness centrality, together with increased betweenness centrality in MCI and dementia participants, suggesting a progressive reorganization of brain network topology. Overall, these findings support the hypothesis that Alzheimer’s disease is associated with specific alterations of structural brain networks that are more readily detected at the level of subnetworks, individual connections, and topological properties than through global connectivity measures alone.