title: Rich club analysis in the Alzheimer's disease connectome reveals a relatively undisturbed structural core network.
abstract: Diffusion imaging can assess the white matter connections within the brain, revealing how neural pathways break down in Alzheimer's disease (AD). We analyzed 3-Tesla whole-brain diffusion-weighted images from 202 participants scanned by the Alzheimer's Disease Neuroimaging Initiative-50 healthy controls, 110 with mild cognitive impairment (MCI) and 42 AD patients. From whole-brain tractography, we reconstructed structural brain connectivity networks to map connections between cortical regions. We tested whether AD disrupts the "rich club" - a network property where high-degree network nodes are more interconnected than expected by chance. We calculated the rich club properties at a range of degree thresholds, as well as other network topology measures including global degree, clustering coefficient, path length, and efficiency. Network disruptions predominated in the low-degree regions of the connectome in patients, relative to controls. The other metrics also showed alterations, suggesting a distinctive pattern of disruption in AD, less pronounced in MCI, targeting global brain connectivity, and focusing on more remotely connected nodes rather than the central core of the network. AD involves severely reduced structural connectivity; our step-wise rich club coefficients analyze points to disruptions predominantly in the peripheral network components; other modalities of data are needed to know if this indicates impaired communication among non rich club regions. The highly connected core was relatively preserved, offering new evidence on the neural basis of progressive risk for cognitive decline.
authors.affiliation: Imaging Genetics Center, Mark & Mary Stevens Institute for Neuroimaging & Informatics, University of Southern California, Marina del Rey, California.
authors.forename: Madelaine
authors.initials: M
authors.lastname: Daianu
authors.affiliation: Imaging Genetics Center, Mark & Mary Stevens Institute for Neuroimaging & Informatics, University of Southern California, Marina del Rey, California.
authors.forename: Neda
authors.initials: N
authors.lastname: Jahanshad
authors.affiliation: Imaging Genetics Center, Mark & Mary Stevens Institute for Neuroimaging & Informatics, University of Southern California, Marina del Rey, California.
authors.forename: Talia M
authors.initials: TM
authors.lastname: Nir
authors.affiliation: Department of Radiology, Mayo Clinic, Rochester, Minnesota.
authors.forename: Clifford R
authors.initials: CR
authors.lastname: Jack
authors.affiliation: Department of Radiology, Medicine, and Psychiatry, University of California San Francisco, California.|Department of Veterans Affairs Medical Center, San Francisco, California.
authors.forename: Michael W
authors.initials: MW
authors.lastname: Weiner
authors.affiliation: Department of Radiology, Mayo Clinic, Rochester, Minnesota.
authors.forename: Matt A
authors.initials: MA
authors.lastname: Bernstein
authors.affiliation: Imaging Genetics Center, Mark & Mary Stevens Institute for Neuroimaging & Informatics, University of Southern California, Marina del Rey, California.|Departments of Neurology, Psychiatry, Radiology, Engineering, Pediatrics, and Ophthalmology, University of Southern California, Los Angeles, California.
authors.forename: Paul M
authors.initials: PM
authors.lastname: Thompson
mesh_terms: D000368:Aged; D000375:Aging / Q000473:pathology; D000544:Alzheimer Disease / Q000473:pathology*; D001921:Brain / Q000473:pathology*; D060825:Cognitive Dysfunction / Q000473:pathology; D063132:Connectome / Q000379:methods*; D038524:Diffusion Magnetic Resonance Imaging / Q000379:methods; D005260:Female; D006801:Humans; D008137:Longitudinal Studies; D008297:Male; D008609:Mental Status Schedule; D009434:Neural Pathways / Q000473:pathology
keywords: Alzheimer's disease; DWI; MRI; graph theory; mild cognitive impairment; rich club