Memory performance-related dynamic brain connectivity indicates pathological burden and genetic risk for Alzheimer's disease

Frances C. Quevenco, Maria G. Preti, Jiri M.G. Van Bergen, Jun Hua, Michael Wyss, Xu Li, Simon J. Schreiner, Stefanie C. Steininger, Rafael Meyer, Irene B. Meier, Adam M. Brickman, Sandra E. Leh, Anton F. Gietl, Alfred Buck, Roger M. Nitsch, Klaas P. Pruessmann, Peter C.M. Van Zijl, Christoph Hock, Dimitri Van De Ville, Paul G. Unschuld

Research output: Contribution to journalArticlepeer-review

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 by 11C 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). Conclusion: 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.

Original languageEnglish (US)
Article number24
JournalAlzheimer's Research and Therapy
Volume9
Issue number1
DOIs
StatePublished - Mar 31 2017

Keywords

  • Alzheimer's disease
  • Amyloid beta
  • Dynamic functional connectivity
  • Episodic memory
  • Iron
  • Oxidative stress

ASJC Scopus subject areas

  • Neurology
  • Clinical Neurology
  • Cognitive Neuroscience

Fingerprint Dive into the research topics of 'Memory performance-related dynamic brain connectivity indicates pathological burden and genetic risk for Alzheimer's disease'. Together they form a unique fingerprint.

Cite this