title: Cortical Amyloid Beta in Cognitively Normal Elderly Adults is Associated with Decreased Network Efficiency within the Cerebro-Cerebellar System.
abstract: BACKGROUND
  Deposition of cortical amyloid beta (Aβ) is a correlate of aging and a risk factor for Alzheimer disease (AD). While several higher order cognitive processes involve functional interactions between cortex and cerebellum, this study aims to investigate effects of cortical Aβ deposition on coupling within the cerebro-cerebellar system.
  
  
  METHODS
  We included 15 healthy elderly subjects with normal cognitive performance as assessed by neuropsychological testing. Cortical Aβ was quantified using (11)carbon-labeled Pittsburgh compound B positron-emission-tomography late frame signals. Volumes of brain structures were assessed by applying an automated parcelation algorithm to three dimensional magnetization-prepared rapid gradient-echo T1-weighted images. Basal functional network activity within the cerebro-cerebellar system was assessed using blood-oxygen-level dependent resting state functional magnetic resonance imaging at the high field strength of 7 T for measuring coupling between cerebellar seeds and cerebral gray matter. A bivariate regression approach was applied for identification of brain regions with significant effects of individual cortical Aβ load on coupling.
  
  
  RESULTS
  Consistent with earlier reports, a significant degree of positive and negative coupling could be observed between cerebellar seeds and cerebral voxels. Significant positive effects of cortical Aβ load on cerebro-cerebellar coupling resulted for cerebral brain regions located in inferior temporal lobe, prefrontal cortex, hippocampus, parahippocampal gyrus, and thalamus.
  
  
  CONCLUSIONS
  Our findings indicate that brain amyloidosis in cognitively normal elderly subjects is associated with decreased network efficiency within the cerebro-cerebellar system. While the identified cerebral regions are consistent with established patterns of increased sensitivity for Aβ-associated neurodegeneration, additional studies are needed to elucidate the relationship between dysfunction of the cerebro-cerebellar system and risk for AD.
authors.affiliation: Division of Psychiatry Research and Psychogeriatric Medicine, University of Zürich , Zürich , Switzerland.
authors.forename: Stefanie C
authors.initials: SC
authors.lastname: Steininger
authors.affiliation: Department of Radiology, Brigham and Women's Hospital, Harvard Medical School , Boston, MA , USA.
authors.forename: Xinyang
authors.initials: X
authors.lastname: Liu
authors.affiliation: Division of Psychiatry Research and Psychogeriatric Medicine, University of Zürich , Zürich , Switzerland.
authors.forename: Anton
authors.initials: A
authors.lastname: Gietl
authors.affiliation: Institute for Biomedical Engineering, University of Zürich, ETH Zürich , Zürich , Switzerland.
authors.forename: Michael
authors.initials: M
authors.lastname: Wyss
authors.affiliation: Division of Psychiatry Research and Psychogeriatric Medicine, University of Zürich , Zürich , Switzerland.
authors.forename: Simon
authors.initials: S
authors.lastname: Schreiner
authors.affiliation: Division of Psychiatry Research and Psychogeriatric Medicine, University of Zürich , Zürich , Switzerland.
authors.forename: Esmeralda
authors.initials: E
authors.lastname: Gruber
authors.affiliation: Division of Psychiatry Research and Psychogeriatric Medicine, University of Zürich , Zürich , Switzerland ; Division of Nuclear Medicine, University of Zürich , Zürich , Switzerland.
authors.forename: Valerie
authors.initials: V
authors.lastname: Treyer
authors.affiliation: Division of Psychiatry Research and Psychogeriatric Medicine, University of Zürich , Zürich , Switzerland.
authors.forename: Andrea
authors.initials: A
authors.lastname: Kälin
authors.affiliation: Division of Psychiatry Research and Psychogeriatric Medicine, University of Zürich , Zürich , Switzerland.
authors.forename: Sandra
authors.initials: S
authors.lastname: Leh
authors.affiliation: Division of Nuclear Medicine, University of Zürich , Zürich , Switzerland.
authors.forename: Alfred
authors.initials: A
authors.lastname: Buck
authors.affiliation: Division of Psychiatry Research and Psychogeriatric Medicine, University of Zürich , Zürich , Switzerland.
authors.forename: Roger M
authors.initials: RM
authors.lastname: Nitsch
authors.affiliation: Institute for Biomedical Engineering, University of Zürich, ETH Zürich , Zürich , Switzerland.
authors.forename: Klaas P
authors.initials: KP
authors.lastname: Prüssmann
authors.affiliation: Division of Psychiatry Research and Psychogeriatric Medicine, University of Zürich , Zürich , Switzerland.
authors.forename: Christoph
authors.initials: C
authors.lastname: Hock
authors.affiliation: Division of Psychiatry Research and Psychogeriatric Medicine, University of Zürich , Zürich , Switzerland.
authors.forename: Paul G
authors.initials: PG
authors.lastname: Unschuld
keywords: Alzheimer disease; aging neuroscience; amyloid beta-peptides; cerebellum; fMRI BOLD; functional connectivity