title: Disrupted Network Topology in Patients with Stable and Progressive Mild Cognitive Impairment and Alzheimer's Disease.
abstract: Recent findings suggest that Alzheimer's disease (AD) is a disconnection syndrome characterized by abnormalities in large-scale networks. However, the alterations that occur in network topology during the prodromal stages of AD, particularly in patients with stable mild cognitive impairment (MCI) and those that show a slow or faster progression to dementia, are still poorly understood. In this study, we used graph theory to assess the organization of structural MRI networks in stable MCI (sMCI) subjects, late MCI converters (lMCIc), early MCI converters (eMCIc), and AD patients from 2 large multicenter cohorts: ADNI and AddNeuroMed. Our findings showed an abnormal global network organization in all patient groups, as reflected by an increased path length, reduced transitivity, and increased modularity compared with controls. In addition, lMCIc, eMCIc, and AD patients showed a decreased path length and mean clustering compared with the sMCI group. At the local level, there were nodal clustering decreases mostly in AD patients, while the nodal closeness centrality detected abnormalities across all patient groups, showing overlapping changes in the hippocampi and amygdala and nonoverlapping changes in parietal, entorhinal, and orbitofrontal regions. These findings suggest that the prodromal and clinical stages of AD are associated with an abnormal network topology.
authors.affiliation: Department of Neurobiology, Care Sciences and Society, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Joana B
authors.initials: JB
authors.lastname: Pereira
authors.affiliation: Department of Physics, Soft Matter Lab.
authors.forename: Mite
authors.initials: M
authors.lastname: Mijalkov
authors.affiliation: Department of Physics, Soft Matter Lab.
authors.forename: Ehsan
authors.initials: E
authors.lastname: Kakaei
authors.affiliation: Institute of Gerontology and Geriatrics, University of Perugia, Perugia, Italy.
authors.forename: Patricia
authors.initials: P
authors.lastname: Mecocci
authors.affiliation: INSERM U 558, University of Toulouse, Toulouse, France.
authors.forename: Bruno
authors.initials: B
authors.lastname: Vellas
authors.affiliation: Aristotle University of Thessaloniki, Thessaloniki, Greece.
authors.forename: Magda
authors.initials: M
authors.lastname: Tsolaki
authors.affiliation: Medical University of Lodz, Lodz, Poland.
authors.forename: Iwona
authors.initials: I
authors.lastname: Kloszewska
authors.affiliation: University of Eastern Finland, Joensuu, Finland.|University Hospital of Kuopio, Kuopio, Finland.
authors.forename: Hilka
authors.initials: H
authors.lastname: Soininen
authors.affiliation: Department of Clinical Science, Intervention and Technology at Karolinska Institutet, Division of Medical Imaging and Technology, Stockholm, Sweden.|Department of Radiology, Karolinska University Hospital in Huddinge, Solna, Sweden.
authors.forename: Christian
authors.initials: C
authors.lastname: Spenger
authors.affiliation: King's College London, Institute of Psychiatry, London, UK.
authors.forename: Simmon
authors.initials: S
authors.lastname: Lovestone
authors.affiliation: NIHR Biomedical Research Centre for Mental Health, London, UK.
authors.forename: Andrew
authors.initials: A
authors.lastname: Simmons
authors.affiliation: Department of Neurobiology, Care Sciences and Society, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Lars-Olof
authors.initials: LO
authors.lastname: Wahlund
authors.affiliation: Department of Physics, Soft Matter Lab.|UNAM-National Nanotechnology Research Center, Bilkent University, Ankara, Turkey.
authors.forename: Giovanni
authors.initials: G
authors.lastname: Volpe
authors.affiliation: Department of Neurobiology, Care Sciences and Society, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Eric
authors.initials: E
authors.lastname: Westman
mesh_terms: D000368:Aged; D000544:Alzheimer Disease / Q000000981:diagnostic imaging / Q000503:physiopathology*; D001921:Brain / Q000000981:diagnostic imaging / Q000503:physiopathology*; D001931:Brain Mapping; D060825:Cognitive Dysfunction / Q000000981:diagnostic imaging / Q000503:physiopathology*; D015331:Cohort Studies; D018450:Disease Progression; D005260:Female; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D009434:Neural Pathways / Q000000981:diagnostic imaging / Q000503:physiopathology
keywords: closeness centrality; clustering; modularity; structural covariance networks; transitivity