title: Memory performance-related dynamic brain connectivity indicates pathological burden and genetic risk for Alzheimer's disease.
abstract: BACKGROUND
  The incidence of Alzheimer's disease (AD) strongly relates to advanced age and progressive deposition of cerebral amyloid-beta (Aβ), hyperphosphorylated tau, and iron. The purpose of this study was to investigate the relationship between cerebral dynamic functional connectivity and variability of long-term cognitive performance in healthy, elderly subjects, allowing for local pathology and genetic risk.
  
  
  METHODS
  Thirty seven participants (mean (SD) age 74 (6.0) years, Mini-Mental State Examination 29.0 (1.2)) were dichotomized based on repeated neuropsychological test performance within 2 years. Cerebral Aβ was measured by11C Pittsburgh Compound-B positron emission tomography, and iron by quantitative susceptibility mapping magnetic resonance imaging (MRI) at an ultra-high field strength of 7 Tesla (7T). Dynamic functional connectivity patterns were investigated by resting-state functional MRI at 7T and tested for interactive effects with genetic AD risk (apolipoprotein E (ApoE)-ε4 carrier status).
  
  
  RESULTS
  A relationship between low episodic memory and a lower expression of anterior-posterior connectivity was seen (F(9,27) = 3.23, p < 0.008), moderated by ApoE-ε4 (F(9,27) = 2.22, p < 0.005). Inherent node-strength was related to local iron (F(5,30) = 13.2; p < 0.022).
  
  
  CONCLUSIONS
  Our data indicate that altered dynamic anterior-posterior brain connectivity is a characteristic of low memory performance in the subclinical range and genetic risk for AD in the elderly. As the observed altered brain network properties are associated with increased local iron, our findings may reflect secondary neuronal changes due to pathologic processes including oxidative stress.
authors.affiliation: Institute for Regenerative Medicine (IREM), University of Zurich, Zurich, Switzerland.
authors.forename: Frances C
authors.initials: FC
authors.lastname: Quevenco
authors.affiliation: Department of Radiology and Medical Informatics, Université de Genève, Geneva, Switzerland.|Institute of Bioengineering, École polytechnique fédérale de Lausanne, Lausanne, Switzerland.
authors.forename: Maria G
authors.initials: MG
authors.lastname: Preti
authors.affiliation: Institute for Regenerative Medicine (IREM), University of Zurich, Zurich, Switzerland.
authors.forename: Jiri M G
authors.initials: JM
authors.lastname: van Bergen
authors.affiliation: Department of Radiology, Johns Hopkins School of Medicine and F.M. Kirby Center for Functional Brain Imaging at Kennedy Krieger Institute, Baltimore, MD, USA.
authors.forename: Jun
authors.initials: J
authors.lastname: Hua
authors.affiliation: Institute for Biomedical Engineering, University of Zurich and ETH Zurich, Zurich, Switzerland.
authors.forename: Michael
authors.initials: M
authors.lastname: Wyss
authors.affiliation: Department of Radiology, Johns Hopkins School of Medicine and F.M. Kirby Center for Functional Brain Imaging at Kennedy Krieger Institute, Baltimore, MD, USA.
authors.forename: Xu
authors.initials: X
authors.lastname: Li
authors.affiliation: Institute for Regenerative Medicine (IREM), University of Zurich, Zurich, Switzerland.|Hospital for Psychogeriatric Medicine, University of Zurich, Minervastr.145, CH-8032, Zurich, Switzerland.
authors.forename: Simon J
authors.initials: SJ
authors.lastname: Schreiner
authors.affiliation: Hospital for Psychogeriatric Medicine, University of Zurich, Minervastr.145, CH-8032, Zurich, Switzerland.
authors.forename: Stefanie C
authors.initials: SC
authors.lastname: Steininger
authors.affiliation: Institute for Regenerative Medicine (IREM), University of Zurich, Zurich, Switzerland.|Hospital for Psychogeriatric Medicine, University of Zurich, Minervastr.145, CH-8032, Zurich, Switzerland.
authors.forename: Rafael
authors.initials: R
authors.lastname: Meyer
authors.affiliation: Institute for Regenerative Medicine (IREM), University of Zurich, Zurich, Switzerland.
authors.forename: Irene B
authors.initials: IB
authors.lastname: Meier
authors.affiliation: Taub Institute for Research on Alzheimer's Disease and the Aging Brain, Department of Neurology, College of Physicians and Surgeons, Columbia University, New York, USA.
authors.forename: Adam M
authors.initials: AM
authors.lastname: Brickman
authors.affiliation: Institute for Regenerative Medicine (IREM), University of Zurich, Zurich, Switzerland.|Hospital for Psychogeriatric Medicine, University of Zurich, Minervastr.145, CH-8032, Zurich, Switzerland.
authors.forename: Sandra E
authors.initials: SE
authors.lastname: Leh
authors.affiliation: Institute for Regenerative Medicine (IREM), University of Zurich, Zurich, Switzerland.|Hospital for Psychogeriatric Medicine, University of Zurich, Minervastr.145, CH-8032, Zurich, Switzerland.
authors.forename: Anton F
authors.initials: AF
authors.lastname: Gietl
authors.affiliation: Division of Nuclear Medicine, University of Zurich, Zurich, Switzerland.
authors.forename: Alfred
authors.initials: A
authors.lastname: Buck
authors.affiliation: Institute for Regenerative Medicine (IREM), University of Zurich, Zurich, Switzerland.|Hospital for Psychogeriatric Medicine, University of Zurich, Minervastr.145, CH-8032, Zurich, Switzerland.
authors.forename: Roger M
authors.initials: RM
authors.lastname: Nitsch
authors.affiliation: Institute for Biomedical Engineering, University of Zurich and ETH Zurich, Zurich, Switzerland.
authors.forename: Klaas P
authors.initials: KP
authors.lastname: Pruessmann
authors.affiliation: Department of Radiology, Johns Hopkins School of Medicine and F.M. Kirby Center for Functional Brain Imaging at Kennedy Krieger Institute, Baltimore, MD, USA.
authors.forename: Peter C M
authors.initials: PC
authors.lastname: van Zijl
authors.affiliation: Institute for Regenerative Medicine (IREM), University of Zurich, Zurich, Switzerland.|Hospital for Psychogeriatric Medicine, University of Zurich, Minervastr.145, CH-8032, Zurich, Switzerland.
authors.forename: Christoph
authors.initials: C
authors.lastname: Hock
authors.affiliation: Department of Radiology and Medical Informatics, Université de Genève, Geneva, Switzerland.|Institute of Bioengineering, École polytechnique fédérale de Lausanne, Lausanne, Switzerland.
authors.forename: Dimitri
authors.initials: D
authors.lastname: Van De Ville
authors.affiliation: Institute for Regenerative Medicine (IREM), University of Zurich, Zurich, Switzerland. paul.unschuld@uzh.ch.|Hospital for Psychogeriatric Medicine, University of Zurich, Minervastr.145, CH-8032, Zurich, Switzerland. paul.unschuld@uzh.ch.
authors.forename: Paul G
authors.initials: PG
authors.lastname: Unschuld
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000000981:diagnostic imaging / Q000235:genetics* / Q000503:physiopathology* / Q000523:psychology; D000814:Aniline Compounds; D053327:Apolipoprotein E4 / Q000235:genetics*; D001921:Brain / Q000000981:diagnostic imaging / Q000503:physiopathology*; D005260:Female; D005500:Follow-Up Studies; D020022:Genetic Predisposition to Disease; D006579:Heterozygote; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D008568:Memory / Q000502:physiology*; D008609:Mental Status Schedule; D008875:Middle Aged; D009483:Neuropsychological Tests; D049268:Positron-Emission Tomography; D019275:Radiopharmaceuticals; D012146:Rest; D013844:Thiazoles
chemical_list: C475519:2-(4'-(methylamino)phenyl)-6-hydroxybenzothiazole; D000814:Aniline Compounds; D053327:Apolipoprotein E4; D019275:Radiopharmaceuticals; D013844:Thiazoles
keywords: Alzheimer’s disease; Amyloid beta; Dynamic functional connectivity; Episodic memory; Iron; Oxidative stress