Epicentral Disruption of Structural Connectivity in Alzheimer's Disease

Carlo Augusto Mallio*, Ruben Schmidt, Marcel A. de Reus, Fabrizio Vernieri, Livia Quintiliani, Giuseppe Curcio, Bruno Beomonte Zobel, Carlo Cosimo Quattrocchi, Martijn P. van den Heuvel

*Corresponding author for this work

Research output: Contribution to JournalArticleAcademicpeer-review


Aims: Neurodegenerative changes observed in Alzheimer's disease (AD) have been suggested to begin at the entorhinal cortex and hippocampus and then to propagate in a stereotypical fashion. Using diffusion-weighted imaging, we test whether disruption of structural connectivity in AD is centered on these "epicenters of disease". Methods: Fifteen healthy controls, 14 amnestic mild cognitive impairment (aMCI), 13 mild, and 15 moderate patients with AD were enrolled. The percentages of affected connections directly linking to the epicenter (named first ring) and to nodes with topological distance 2 from the epicenter (named second ring) were calculated. Results: For the group of aMCI patients, just 5.3% of the first ring (n.s.) and 2.9% of the second ring (n.s.) connections were affected. However, for mild AD there was disruption involving 20% of the first ring (P < 0.0001) and 10.3% of the second ring (P < 0.0001) connections. In the moderate AD group, a stronger effect was observed, with 38.0% of the first ring (P < 0.0001) connections and 17.9% of the second ring (P < 0.0001) connections affected. Conclusion: Our results favor an epicentral disruption of structural connectivity in aMCI and AD around entorhinal and hippocampal regions, consistent with the transneuronal spread hypothesis.

Original languageEnglish
Pages (from-to)837-845
Number of pages9
JournalCNS Neuroscience and Therapeutics
Issue number10
Publication statusPublished - 1 Oct 2015
Externally publishedYes


  • Alzheimer's Disease
  • Connectivity
  • Connectome
  • Diffusion-weighted imaging
  • Epicentral disruption
  • Mild cognitive impairment


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