Left Frontal Hub Connectivity during Memory Performance Supports Reserve in Aging and Mild Cognitive Impairment

Nicolai Franzmeier, Julia Hartmann, Alexander N. W. Taylor, Miguel A. Araque Caballero, Lee Simon-Vermot, Katharina Beurger, Lana Kambeitz-Ilankovic, Birgit Ertl-Wagner, Claudia Mueller, Cihan Catak, Daniel Janowitz, Robert Stahl, Martin Dichgans, Marco Duering, Michael Ewers

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Reserve in aging and Alzheimer’s disease (AD) is defined as maintaining cognition at a relatively high level in the presence of neurodegeneration, an ability often associated with higher education among other life factors. Recent evidence suggests that higher resting-state functional connectivity within the frontoparietal control network, specifically the left frontal cortex (LFC) hub, contributes to higher reserve. Following up these previous resting-state fMRI findings, we probed memory-task related functional connectivity of the LFC hub as a neural substrate of reserve. In elderly controls (CN, n = 37) and patients with mild cognitive impairment (MCI, n = 17), we assessed global connectivity of the LFC hub during successful face-name association learning, using generalized psychophysiological interaction analyses. Reserve was quantified as residualized memory performance, accounted for gender and proxies of neurodegeneration (age, hippocampus atrophy, and APOE genotype). We found that greater education was associated with higher LFC-connectivity in both CN and MCI during successful memory. Furthermore, higher LFC-connectivity predicted higher residualized memory (i.e., reserve). These results suggest that higher LFC-connectivity contributes to reserve in both healthy and pathological aging.
Original languageEnglish
Pages (from-to)1381-1392
Number of pages12
JournalJournal of Alzheimer’s Disease
Issue number4
Publication statusPublished - 14 Aug 2017
Externally publishedYes


  • Aging
  • cognitive reserve
  • education
  • Functional connectivity
  • memory
  • mild cognitive impairment
  • task-fMRI
  • functional connectivity
  • Apolipoproteins E/genetics
  • Frontal Lobe/diagnostic imaging
  • Humans
  • Male
  • Nerve Net/diagnostic imaging
  • Aging/pathology
  • Names
  • Memory/physiology
  • Aged, 80 and over
  • Female
  • Face
  • Functional Laterality/physiology
  • Neural Pathways/diagnostic imaging
  • Magnetic Resonance Imaging
  • Image Processing, Computer-Assisted
  • Sex Factors
  • Brain Mapping
  • Pattern Recognition, Visual/physiology
  • Aged
  • Cognitive Dysfunction/diagnostic imaging


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