Functional Disintegration of the Default Mode Network in Prodromal Alzheimer's Disease

Kim N. H. Dillen*, Heidi I. L. Jacobs, Juraj Kukolja, Nils Richter, Boris von Reutern, Ozgur A. Onur, Karl-Josef Langen, Gereon R. Fink

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

56 Citations (Web of Science)

Abstract

Neurodegenerative brain changes can affect the functional connectivity strength between nodes of the default-mode network (DMN), which may underlie changes in cognitive performance. It remains unclear how the functional connectivity strength of DMN nodes differs from healthy to pathological aging and whether these changes are cognitively relevant. We used resting-state functional magnetic resonance imaging to investigate the functional connectivity strength across five DMN nodes in 25 healthy controls (HC), 28 subjective cognitive decline (SCD) participants, and 25 prodromal Alzheimer's disease (AD) patients. After identifying the ventral medial prefrontal cortex (vmPFC), posterior cingulate cortex (PCC), retrosplenial cortex (RSC), inferior parietal lobule, and the hippocampus we investigated the functional strength between DMN nodes using temporal network modeling. Functional coupling of the vmPFC and PCC in prodromal AD patients was disrupted. This vmPFC-PCC coupling correlated positively with memory performance in prodromal AD. Furthermore, the hippocampus de-coupled from posterior DMN nodes in SCD and prodromal AD patients. There was no coupling between the hippocampus and the anterior DMN. Additional mediation analyses indicated that the RSC enables communication between the hippocampus and DMN regions in HC but none of the other two groups. These results suggest an anterior-posterior disconnection and a hippocampal de-coupling from posterior DMN nodes with disease progression. Hippocampal de-coupling already occurring in SCD may provide valuable information for the development of a functional biomarker.

Original languageEnglish
Pages (from-to)169-187
Number of pages19
JournalJournal of Alzheimer's Disease
Volume59
Issue number1
DOIs
Publication statusPublished - 2017

Keywords

  • Dementia
  • functional MRI
  • hippocampus
  • memory
  • MILD COGNITIVE IMPAIRMENT
  • RESTING-STATE FMRI
  • INDEPENDENT COMPONENT ANALYSIS
  • POSTERIOR CINGULATE CORTEX
  • HUMAN BRAIN
  • CORTICAL HUBS
  • IN-VIVO
  • ASSOCIATION WORKGROUPS
  • DISCONNECTION SYNDROME
  • DIAGNOSTIC GUIDELINES

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