title: Tract-specific white matter hyperintensities disrupt neural network function in Alzheimer's disease.
abstract: BACKGROUND
  White matter hyperintensities (WMHs) increase the risk of Alzheimer's disease (AD). Whether WMHs are associated with the decline of functional neural networks in AD is debated.
  
  
  METHODS
  Resting-state functional magnetic resonance imaging and WMH were assessed in 78 subjects with increased amyloid levels on AV-45 positron emission tomography (PET) in different clinical stages of AD. We tested the association between WMH volume in major atlas-based fiber tract regions of interest (ROIs) and changes in functional connectivity (FC) between the tracts' projection areas within the default mode network (DMN).
  
  
  RESULTS
  WMH volume within the inferior fronto-occipital fasciculus (IFOF) was the highest among all tract ROIs and associated with reduced FC in IFOF-connected DMN areas, independently of global AV-45 PET. Higher AV-45 PET contributed to reduced FC in IFOF-connected, temporal, and parietal DMN areas.
  
  
  CONCLUSIONS
  High fiber tract WMH burden is associated with reduced FC in connected areas, thus adding to the effects of amyloid pathology on neuronal network function.
authors.affiliation: Institute for Stroke and Dementia Research, Klinikum der Universität München, Ludwig-Maximilians-Universität LMU, Munich, Germany.
authors.forename: Alexander N W
authors.initials: ANW
authors.lastname: Taylor
authors.affiliation: Department of Psychiatry and Psychotherapy, Ludwig-Maximilians-Universität LMU, Munich, Germany.
authors.forename: Lana
authors.initials: L
authors.lastname: Kambeitz-Ilankovic
authors.affiliation: Institute for Stroke and Dementia Research, Klinikum der Universität München, Ludwig-Maximilians-Universität LMU, Munich, Germany.
authors.forename: Benno
authors.initials: B
authors.lastname: Gesierich
authors.affiliation: Institute for Stroke and Dementia Research, Klinikum der Universität München, Ludwig-Maximilians-Universität LMU, Munich, Germany.
authors.forename: Lee
authors.initials: L
authors.lastname: Simon-Vermot
authors.affiliation: Institute for Stroke and Dementia Research, Klinikum der Universität München, Ludwig-Maximilians-Universität LMU, Munich, Germany.
authors.forename: Nicolai
authors.initials: N
authors.lastname: Franzmeier
authors.affiliation: Institute for Stroke and Dementia Research, Klinikum der Universität München, Ludwig-Maximilians-Universität LMU, Munich, Germany.
authors.forename: Miguel Á
authors.initials: MÁ
authors.lastname: Araque Caballero
authors.affiliation: Institute of Clinical Radiology, Klinikum der Universität München, Ludwig-Maximilians-Universität LMU, Munich, Germany.
authors.forename: Sophia
authors.initials: S
authors.lastname: Müller
authors.affiliation: Athinoula A. Martinos Center for Biomedical Imaging, Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA, USA.
authors.forename: Liu
authors.initials: L
authors.lastname: Hesheng
authors.affiliation: Institute of Clinical Radiology, Klinikum der Universität München, Ludwig-Maximilians-Universität LMU, Munich, Germany.
authors.forename: Birgit
authors.initials: B
authors.lastname: Ertl-Wagner
authors.affiliation: Institute of Clinical Radiology, Klinikum der Universität München, Ludwig-Maximilians-Universität LMU, Munich, Germany.
authors.forename: Katharina
authors.initials: K
authors.lastname: Bürger
authors.affiliation: Department of Radiology & Biomedical Imaging, University of California, San Francisco, CA, USA; VA Medical Center, Center for Imaging of Neurodegenerative Diseases, San Francisco, CA, USA.
authors.forename: Michael W
authors.initials: MW
authors.lastname: Weiner
authors.affiliation: Institute for Stroke and Dementia Research, Klinikum der Universität München, Ludwig-Maximilians-Universität LMU, Munich, Germany; Munich Cluster for Systems Neurology (SyNergy), Munich, Germany.
authors.forename: Martin
authors.initials: M
authors.lastname: Dichgans
authors.affiliation: Institute for Stroke and Dementia Research, Klinikum der Universität München, Ludwig-Maximilians-Universität LMU, Munich, Germany.
authors.forename: Marco
authors.initials: M
authors.lastname: Duering
authors.affiliation: Institute for Stroke and Dementia Research, Klinikum der Universität München, Ludwig-Maximilians-Universität LMU, Munich, Germany. Electronic address: michael.ewers@med.uni-muenchen.de.
authors.forename: Michael
authors.initials: M
authors.lastname: Ewers
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000000981:diagnostic imaging / Q000473:pathology* / Q000503:physiopathology*; D001931:Brain Mapping; D005260:Female; D006801:Humans; D007091:Image Processing, Computer-Assisted; D008279:Magnetic Resonance Imaging; D008297:Male; D009415:Nerve Net / Q000000981:diagnostic imaging / Q000473:pathology*; D009483:Neuropsychological Tests; D049268:Positron-Emission Tomography; D066127:White Matter / Q000000981:diagnostic imaging / Q000473:pathology*
keywords: Alzheimer's disease; Amyloid-beta; Fiber tract; Functional connectivity; Resting-state fMRI; Vascular; White matter hyperintensities