title: SPECTRAL GRAPH THEORY AND GRAPH ENERGY METRICS SHOW EVIDENCE FOR THE ALZHEIMER'S DISEASE DISCONNECTION SYNDROME INAPOE-4 RISK GENE CARRIERS.
abstract: Our understanding of network breakdown in Alzheimer's disease (AD) is likely to be enhanced through advanced mathematical descriptors. Here, we applied spectral graph theory to provide novel metrics of structural connectivity based on 3-Tesla diffusion weighted images in 42 AD patients and 50 healthy controls. We reconstructed connectivity networks using whole-brain tractography and examined, for the first time here, cortical disconnection based on the graph energy and spectrum. We further assessed supporting metrics - link density and nodal strength - to better interpret our results. Metrics were analyzed in relation to the well-knownAPOE-4 genetic risk factor for late-onset AD. The number of disconnected cortical regions increased with the number of copies of theAPOE-4 risk gene in people with AD. Each additional copy of theAPOE-4 risk gene may lead to more dysfunctional networks with weakened or abnormal connections, providing evidence for the previously hypothesized "disconnection syndrome".
authors.affiliation: Imaging Genetics Center, Institute for Neuroimaging & Informatics, University of Southern California.
authors.forename: Madelaine
authors.initials: M
authors.lastname: Daianu
authors.affiliation: Imaging Genetics Center, Institute for Neuroimaging & Informatics, University of Southern California.
authors.forename: Adam
authors.initials: A
authors.lastname: Mezher
authors.affiliation: Imaging Genetics Center, Institute for Neuroimaging & Informatics, University of Southern California.
authors.forename: Neda
authors.initials: N
authors.lastname: Jahanshad
authors.affiliation: Imaging Genetics Center, Institute for Neuroimaging & Informatics, University of Southern California.
authors.forename: Derrek P
authors.initials: DP
authors.lastname: Hibar
authors.affiliation: Imaging Genetics Center, Institute for Neuroimaging & Informatics, University of Southern California.
authors.forename: Talia M
authors.initials: TM
authors.lastname: Nir
authors.affiliation: Department of Radiology, Mayo Clinic, Rochester, Minnesota, USA.
authors.forename: Clifford R
authors.initials: CR
authors.lastname: Jack
authors.affiliation: Department of Radiology, Medicine, and Psychiatry, University of California San Francisco, CA, USA ; Department of Veterans Affairs Medical Center, San Francisco, CA, USA.
authors.forename: Michael W
authors.initials: MW
authors.lastname: Weiner
authors.affiliation: Department of Radiology, Mayo Clinic, Rochester, Minnesota, USA.
authors.forename: Matt A
authors.initials: MA
authors.lastname: Bernstein
authors.affiliation: Imaging Genetics Center, Institute for Neuroimaging & Informatics, University of Southern California.
authors.forename: Paul M
authors.initials: PM
authors.lastname: Thompson
keywords: APOE-4; Alzheimer’s disease; disconnection syndrome; energy; graph spectrum