The left frontal cortex supports reserve in aging by enhancing functional network efficiency

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

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Background: Recent evidence from fMRI studies suggests that functional hubs, i.e. highly connected brain regions, are important for mental health. We found recently that global connectivity of a hub in the left frontal cortex (LFC-connectivity) is associated with relatively preserved memory abilities and higher levels of protective factors (education, IQ) in normal aging and Alzheimer’s disease. These results suggest that LFC-connectivity supports reserve capacity alleviating memory decline. An open question is, however, why LFC-connectivity is beneficial and supports memory function in the face of neurodegeneration. We hypothesized that higher LFCconnectivity is associated with enhanced efficiency in connected major networks involved in episodic memory. We further hypothesized that higher LFC-related network efficiency predicts higher memory abilities.

Methods: We assessed fMRI during a face-name association learning task in 26 healthy cognitively normal elderly participants. Using beta-series correlation analysis, we computed task-related LFC-connectivity to key memory networks including the default-mode network (DMN) and dorsal attention network (DAN). Network efficiency within the DMN and DAN was estimated by the graph theoretical small-worldness statistic. We applied linear regression analyses in
order to test the association between LFC-connectivity to the DMN/DAN and small-worldness of these networks. Mediation analysis was applied to test LFC-connectivity to the DMN and DAN as a mediator of the association between education and higher DMN and DAN smallworldness. Lastly, we tested network small-worldness as a predictor of memory performance.

Results: We found that higher LFC-connectivity to the DMN and DAN during successful memory encoding and recognition was associated with higher small-worldness of those networks. Higher task-related LFC-connectivity mediated the association between education and higher small-worldness in the DMN and DAN. Further, higher small-worldness of these networks predicted better performance in the memory task.

Conclusions: The current results suggest that higher education-related LFC-connectivity to key memory networks during a memory task is associated with higher network efficiency and thus enhanced reserve of memory abilities in aging.
Original languageEnglish
Article number28
JournalAlzheimer's Research & Therapy
Publication statusPublished - 6 Mar 2018


  • Cognitive reserve
  • Aging
  • memory task-fMRI
  • small-worldness
  • Fronto-parietal control network

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