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Cognitive reserve against Alzheimer’s pathology is linked to brain activity during memory formation

Niklas Vockert (), Judith Machts, Luca Kleineidam, Aditya Nemali, Enise I. Incesoy, Jose Bernal, Hartmut Schütze, Renat Yakupov, Oliver Peters, Daria Gref, Luisa Sophie Schneider, Lukas Preis, Josef Priller, Eike Jakob Spruth, Slawek Altenstein, Anja Schneider, Klaus Fliessbach, Jens Wiltfang, Ayda Rostamzadeh, Wenzel Glanz, Stefan Teipel, Ingo Kilimann, Doreen Goerss, Christoph Laske, Matthias H. Munk, Annika Spottke, Nina Roy, Michael T. Heneka, Frederic Brosseron, Michael Wagner, Steffen Wolfsgruber, Laura Dobisch, Peter Dechent, Stefan Hetzer, Klaus Scheffler, Peter Zeidman, Yaakov Stern, Björn H. Schott, Frank Jessen, Emrah Düzel, Anne Maass () and Gabriel Ziegler ()
Additional contact information
Niklas Vockert: German Center for Neurodegenerative Diseases (DZNE)
Judith Machts: German Center for Neurodegenerative Diseases (DZNE)
Luca Kleineidam: German Center for Neurodegenerative Diseases (DZNE)
Aditya Nemali: German Center for Neurodegenerative Diseases (DZNE)
Enise I. Incesoy: German Center for Neurodegenerative Diseases (DZNE)
Jose Bernal: German Center for Neurodegenerative Diseases (DZNE)
Hartmut Schütze: German Center for Neurodegenerative Diseases (DZNE)
Renat Yakupov: German Center for Neurodegenerative Diseases (DZNE)
Oliver Peters: German Center for Neurodegenerative Diseases (DZNE)
Daria Gref: Institute of Psychiatry and Psychotherapy
Luisa Sophie Schneider: ECRC Experimental and Clinical Research Center
Lukas Preis: Institute of Psychiatry and Psychotherapy
Josef Priller: German Center for Neurodegenerative Diseases (DZNE)
Eike Jakob Spruth: German Center for Neurodegenerative Diseases (DZNE)
Slawek Altenstein: German Center for Neurodegenerative Diseases (DZNE)
Anja Schneider: German Center for Neurodegenerative Diseases (DZNE)
Klaus Fliessbach: German Center for Neurodegenerative Diseases (DZNE)
Jens Wiltfang: German Center for Neurodegenerative Diseases (DZNE)
Ayda Rostamzadeh: German Center for Neurodegenerative Diseases (DZNE)
Wenzel Glanz: German Center for Neurodegenerative Diseases (DZNE)
Stefan Teipel: German Center for Neurodegenerative Diseases (DZNE)
Ingo Kilimann: German Center for Neurodegenerative Diseases (DZNE)
Doreen Goerss: German Center for Neurodegenerative Diseases (DZNE)
Christoph Laske: German Center for Neurodegenerative Diseases (DZNE)
Matthias H. Munk: German Center for Neurodegenerative Diseases (DZNE)
Annika Spottke: German Center for Neurodegenerative Diseases (DZNE)
Nina Roy: German Center for Neurodegenerative Diseases (DZNE)
Michael T. Heneka: German Center for Neurodegenerative Diseases (DZNE)
Frederic Brosseron: German Center for Neurodegenerative Diseases (DZNE)
Michael Wagner: German Center for Neurodegenerative Diseases (DZNE)
Steffen Wolfsgruber: German Center for Neurodegenerative Diseases (DZNE)
Laura Dobisch: German Center for Neurodegenerative Diseases (DZNE)
Peter Dechent: Georg-August-University Goettingen
Stefan Hetzer: Charité - Universitaetsmedizin Berlin
Klaus Scheffler: University of Tuebingen
Peter Zeidman: UCL Institute of Neurology
Yaakov Stern: Columbia University Vagelos College of Physicians and Surgeons
Björn H. Schott: German Center for Neurodegenerative Diseases (DZNE)
Frank Jessen: German Center for Neurodegenerative Diseases (DZNE)
Emrah Düzel: German Center for Neurodegenerative Diseases (DZNE)
Anne Maass: German Center for Neurodegenerative Diseases (DZNE)
Gabriel Ziegler: German Center for Neurodegenerative Diseases (DZNE)

Nature Communications, 2024, vol. 15, issue 1, 1-16

Abstract: Abstract The cognitive reserve (CR) hypothesis posits that individuals can differ in how their brain function is disrupted by pathology associated with aging and neurodegeneration. Here, we test this hypothesis in the continuum from cognitively normal to at-risk stages for Alzheimer’s Disease (AD) to AD dementia using longitudinal data from 490 participants of the DELCODE multicentric observational study. Brain function is measured using task fMRI of visual memory encoding. Using a multivariate moderation analysis, we identify a CR-related activity pattern underlying successful memory encoding that moderates the detrimental effect of AD pathological load on cognitive performance. CR is mainly represented by a more pronounced expression of the task-active network encompassing deactivation of the default mode network (DMN) and activation of inferior temporal regions including the fusiform gyrus. We devise personalized fMRI-based CR scores that moderate the impact of AD pathology on cognitive performance and are positively associated with years of education. Furthermore, higher CR scores attenuate the effect of AD pathology on cognitive decline over time. Our findings primarily provide evidence for the maintenance of core cognitive circuits including the DMN as the neural basis of CR. Individual brain activity levels of these areas during memory encoding have prognostic value for future cognitive decline.

Date: 2024
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Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-53360-9

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DOI: 10.1038/s41467-024-53360-9

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