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A Residual Marker of Cognitive Reserve Is Associated with Resting-State Intrinsic Functional Connectivity Along the Alzheimer's Disease Continuum.

Journal of Alzheimer's disease : JAD

Authors: Ersin Ersoezlue, Robert Perneczky, Maia Tato, Julia Utecht, Carolin Kurz, Jan Häckert, Selim Guersel, Lena Burow, Gabriele Koller, Sophia Stoecklein, Daniel Keeser, Boris Papazov, Marie Totzke, Tommaso Ballarini, Frederic Brosseron, Katharina Buerger, Peter Dechent, Laura Dobisch, Michael Ewers, Klaus Fliessbach, Wenzel Glanz, John Dylan Haynes, Michael T Heneka, Daniel Janowitz, Ingo Kilimann, Luca Kleineidam, Christoph Laske, Franziska Maier, Matthias H Munk, Oliver Peters, Josef Priller, Alfredo Ramirez, Sandra Roeske, Nina Roy, Klaus Scheffler, Anja Schneider, Björn H Schott, Annika Spottke, Eike J Spruth, Stefan Teipel, Chantal Unterfeld, Michael Wagner, Xiao Wang, Jens Wiltfang, Steffen Wolfsgruber, Renat Yakupov, Emrah Duezel, Frank Jessen, Boris-Stephan Rauchmann

BACKGROUND: Cognitive reserve (CR) explains inter-individual differences in the impact of the neurodegenerative burden on cognitive functioning. A residual model was proposed to estimate CR more accurately than previous measures. However, associations between residual CR markers (CRM) and functional connectivity (FC) remain unexplored.

OBJECTIVE: To explore the associations between the CRM and intrinsic network connectivity (INC) in resting-state networks along the neuropathological-continuum of Alzheimer's disease (ADN).

METHODS: Three hundred eighteen participants from the DELCODE cohort were stratified using cerebrospinal fluid biomarkers according to the A(myloid-β)/T(au)/N(eurodegeneration) classification. CRM was calculated utilizing residuals obtained from a multilinear regression model predicting cognition from markers of disease burden. Using an independent component analysis in resting-state fMRI data, we measured INC of resting-state networks, i.e., default mode network (DMN), frontoparietal network (FPN), salience network (SAL), and dorsal attention network. The associations of INC with a composite memory score and CRM and the associations of CRM with the seed-to-voxel functional connectivity of memory-related were tested in general linear models.

RESULTS: CRM was positively associated with INC in the DMN in the entire cohort. The A+T+N+ group revealed an anti-correlation between the SAL and the DMN. Furthermore, CRM was positively associated with anti-correlation between memory-related regions in FPN and DMN in ADN and A+T/N+.

CONCLUSION: Our results provide evidence that INC is associated with CRM in ADN defined as participants with amyloid pathology with or without cognitive symptoms, suggesting that the neural correlates of CR are mirrored in network FC in resting-state.

PMID: 36806502

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