title: Small vessel disease is linked to disrupted structural network covariance in Alzheimer's disease.
abstract: BACKGROUND
  Cerebral small vessel disease (SVD) is thought to contribute to Alzheimer's disease (AD) through abnormalities in white matter networks. Gray matter (GM) hub covariance networks share only partial overlap with white matter connectivity, and their relationship with SVD has not been examined in AD.
  
  
  METHODS
  We developed a multivariate analytical pipeline to elucidate the cortical GM thickness systems that covary with major network hubs and assessed whether SVD and neurodegenerative pathologic markers were associated with attenuated covariance network integrity in mild AD and normal elderly control subjects.
  
  
  RESULTS
  SVD burden was associated with reduced posterior cingulate corticocortical GM network integrity and subneocorticocortical hub network integrity in AD.
  
  
  CONCLUSIONS
  These findings provide evidence that SVD is linked to the selective disruption of cortical hub GM networks in AD brains and point to the need to consider GM hub covariance networks when assessing network disruption in mixed disease.
authors.affiliation: LC Campbell Cognitive Neurology Research Unit, Ontario, Canada; Heart and Stroke Foundation Canadian Partnership for Stroke Recovery, Ontario, Canada; Hurvitz Brain Sciences Research Program, Sunnybrook Research Institute, University of Toronto, Ontario, Canada; Institute of Medical Science, University of Toronto, Ontario, Canada; MD/PhD Program, Faculty of Medicine, University of Toronto, Ontario, Canada. Electronic address: sean.nestor@mail.utoronto.ca.
authors.forename: Sean M
authors.initials: SM
authors.lastname: Nestor
authors.affiliation: Department of Psychological and Brain Sciences, Indiana University, IN, USA.
authors.forename: Bratislav
authors.initials: B
authors.lastname: Mišić
authors.affiliation: LC Campbell Cognitive Neurology Research Unit, Ontario, Canada; Heart and Stroke Foundation Canadian Partnership for Stroke Recovery, Ontario, Canada; Hurvitz Brain Sciences Research Program, Sunnybrook Research Institute, University of Toronto, Ontario, Canada.
authors.forename: Joel
authors.initials: J
authors.lastname: Ramirez
authors.affiliation: LC Campbell Cognitive Neurology Research Unit, Ontario, Canada; Heart and Stroke Foundation Canadian Partnership for Stroke Recovery, Ontario, Canada.
authors.forename: Jiali
authors.initials: J
authors.lastname: Zhao
authors.affiliation: Heart and Stroke Foundation Canadian Partnership for Stroke Recovery, Ontario, Canada; Hurvitz Brain Sciences Research Program, Sunnybrook Research Institute, University of Toronto, Ontario, Canada; Department of Medical Biophysics, University of Toronto, Ontario, Canada.
authors.forename: Simon J
authors.initials: SJ
authors.lastname: Graham
authors.affiliation: Department of Psychiatry, Baycrest Health Sciences Centre and University of Toronto, Ontario, Canada.
authors.forename: Nicolaas P L G
authors.initials: NPLG
authors.lastname: Verhoeff
authors.affiliation: Hurvitz Brain Sciences Research Program, Sunnybrook Research Institute, University of Toronto, Ontario, Canada; Department of Medicine, University of Toronto, Ontario, Canada; Department of Psychology, University of Toronto, Ontario, Canada; Rotman Research Institute, Baycrest Health Sciences Centre, Ontario, Canada.
authors.forename: Donald T
authors.initials: DT
authors.lastname: Stuss
authors.affiliation: LC Campbell Cognitive Neurology Research Unit, Ontario, Canada; Heart and Stroke Foundation Canadian Partnership for Stroke Recovery, Ontario, Canada; Hurvitz Brain Sciences Research Program, Sunnybrook Research Institute, University of Toronto, Ontario, Canada; Institute of Medical Science, University of Toronto, Ontario, Canada; Department of Medicine, Neurology, Sunnybrook Health Sciences Centre, University of Toronto, Ontario, Canada.
authors.forename: Mario
authors.initials: M
authors.lastname: Masellis
authors.affiliation: LC Campbell Cognitive Neurology Research Unit, Ontario, Canada; Heart and Stroke Foundation Canadian Partnership for Stroke Recovery, Ontario, Canada; Hurvitz Brain Sciences Research Program, Sunnybrook Research Institute, University of Toronto, Ontario, Canada; Institute of Medical Science, University of Toronto, Ontario, Canada; Rotman Research Institute, Baycrest Health Sciences Centre, Ontario, Canada; Department of Medicine, Neurology, Sunnybrook Health Sciences Centre, University of Toronto, Ontario, Canada; Ontario Brain Institute, Ontario, Canada.
authors.forename: Sandra E
authors.initials: SE
authors.lastname: Black
mesh_terms: D000368:Aged; D000544:Alzheimer Disease / Q000000981:diagnostic imaging / Q000473:pathology*; D001921:Brain / Q000473:pathology; D059345:Cerebral Small Vessel Diseases / Q000473:pathology*; D005260:Female; D006801:Humans; D007091:Image Processing, Computer-Assisted; D008279:Magnetic Resonance Imaging / Q000379:methods; D008297:Male; D009434:Neural Pathways / Q000473:pathology*; D011446:Prospective Studies; D066127:White Matter
keywords: Alzheimer's disease; Cortical thickness; Hippocampal volume; Magnetic resonance imaging; Partial least squares; Rich-Club network; Shape analysis; Small vessel disease; Structural covariance networks; White matter hyperintensity