title: Epicentral disruption of structural connectivity in Alzheimer's disease.
abstract: OBJECTIVE
  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.
  
  
  CONCLUSIONS
  Our results favor an epicentral disruption of structural connectivity in aMCI and AD around entorhinal and hippocampal regions, consistent with the transneuronal spread hypothesis.
authors.affiliation: Departmental Faculty of Medicine and Surgery, Unit of Diagnostic Imaging, Università Campus Bio-Medico di Roma, Rome, Italy.
authors.forename: Carlo Augusto
authors.initials: CA
authors.lastname: Mallio
authors.affiliation: Brain Center Rudolf Magnus, Department of Neurology, University Medical Center Utrecht, Utrecht, the Netherlands.
authors.forename: Ruben
authors.initials: R
authors.lastname: Schmidt
authors.affiliation: Brain Center Rudolf Magnus, Department of Psychiatry, University Medical Center Utrecht, Utrecht, the Netherlands.
authors.forename: Marcel A
authors.initials: MA
authors.lastname: de Reus
authors.affiliation: Departmental Faculty of Medicine and Surgery, Unit of Neurology, Università Campus Bio-Medico di Roma, Rome, Italy.
authors.forename: Fabrizio
authors.initials: F
authors.lastname: Vernieri
authors.affiliation: Departmental Faculty of Medicine and Surgery, Unit of Neurology, Università Campus Bio-Medico di Roma, Rome, Italy.
authors.forename: Livia
authors.initials: L
authors.lastname: Quintiliani
authors.affiliation: Department of Life, Health and Environmental Sciences, University of L'Aquila, L'Aquila, Italy.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Curcio
authors.affiliation: Departmental Faculty of Medicine and Surgery, Unit of Diagnostic Imaging, Università Campus Bio-Medico di Roma, Rome, Italy.
authors.forename: Bruno
authors.initials: B
authors.lastname: Beomonte Zobel
authors.affiliation: Departmental Faculty of Medicine and Surgery, Unit of Diagnostic Imaging, Università Campus Bio-Medico di Roma, Rome, Italy.
authors.forename: Carlo Cosimo
authors.initials: CC
authors.lastname: Quattrocchi
authors.affiliation: Brain Center Rudolf Magnus, Department of Psychiatry, University Medical Center Utrecht, Utrecht, the Netherlands.
authors.forename: Martijn P
authors.initials: MP
authors.lastname: van den Heuvel
mesh_terms: D000368:Aged; D000544:Alzheimer Disease / Q000473:pathology*; D016880:Anisotropy; D001921:Brain / Q000473:pathology*; D060825:Cognitive Dysfunction / Q000473:pathology; D005260:Female; D006801:Humans; D007091:Image Processing, Computer-Assisted; D008279:Magnetic Resonance Imaging / Q000379:methods; D008297:Male; D008609:Mental Status Schedule; D009434:Neural Pathways / Q000473:pathology; D012720:Severity of Illness Index
keywords: Alzheimer's Disease; Connectivity; Connectome; Diffusion-weighted imaging; Epicentral disruption; Mild cognitive impairment