[en] 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.
Disciplines :
Neurology
Author, co-author :
Vockert, Niklas ; German Center for Neurodegenerative Diseases (DZNE), Magdeburg, Germany. Niklas.Vockert@dzne.de
Machts, Judith; German Center for Neurodegenerative Diseases (DZNE), Magdeburg, Germany ; Institute of Cognitive Neurology and Dementia Research (IKND), Otto-von-Guericke University, Magdeburg, Germany
Kleineidam, Luca ; German Center for Neurodegenerative Diseases (DZNE), Bonn, Germany ; University of Bonn Medical Center, Department of Neurodegenerative Diseases and Geriatric Psychiatry, Bonn, Germany
Nemali, Aditya; German Center for Neurodegenerative Diseases (DZNE), Magdeburg, Germany ; Institute of Cognitive Neurology and Dementia Research (IKND), Otto-von-Guericke University, Magdeburg, Germany
Incesoy, Enise I ; German Center for Neurodegenerative Diseases (DZNE), Magdeburg, Germany ; Institute of Cognitive Neurology and Dementia Research (IKND), Otto-von-Guericke University, Magdeburg, Germany ; Department for Psychiatry and Psychotherapy, University Clinic Magdeburg, Magdeburg, Germany
Bernal, Jose; German Center for Neurodegenerative Diseases (DZNE), Magdeburg, Germany ; Institute of Cognitive Neurology and Dementia Research (IKND), Otto-von-Guericke University, Magdeburg, Germany
Schütze, Hartmut ; German Center for Neurodegenerative Diseases (DZNE), Magdeburg, Germany ; Institute of Cognitive Neurology and Dementia Research (IKND), Otto-von-Guericke University, Magdeburg, Germany
Yakupov, Renat ; German Center for Neurodegenerative Diseases (DZNE), Magdeburg, Germany ; Institute of Cognitive Neurology and Dementia Research (IKND), Otto-von-Guericke University, Magdeburg, Germany
Peters, Oliver; German Center for Neurodegenerative Diseases (DZNE), Berlin, Germany ; Charité - Universitaetsmedizin Berlin, corporate member of Freie Universitaet Berlin and Humboldt-Universitaet zu Berlin, Institute of Psychiatry and Psychotherapy, Berlin, Germany
Gref, Daria ; Charité - Universitaetsmedizin Berlin, corporate member of Freie Universitaet Berlin and Humboldt-Universitaet zu Berlin, Institute of Psychiatry and Psychotherapy, Berlin, Germany
Schneider, Luisa Sophie ; Charité - Universitaetsmedizin Berlin, corporate member of Freie Universitaet Berlin and Humboldt-Universitaet zu Berlin, ECRC Experimental and Clinical Research Center, Berlin, Germany
Preis, Lukas; Charité - Universitaetsmedizin Berlin, corporate member of Freie Universitaet Berlin and Humboldt-Universitaet zu Berlin, Institute of Psychiatry and Psychotherapy, Berlin, Germany
Priller, Josef ; German Center for Neurodegenerative Diseases (DZNE), Berlin, Germany ; Department of Psychiatry and Psychotherapy, Charité Berlin, Germany ; School of Medicine, Technical University of Munich, Department of Psychiatry and Psychotherapy, Munich, Germany ; University of Edinburgh and UK DRI, Edinburgh, UK
Spruth, Eike Jakob; German Center for Neurodegenerative Diseases (DZNE), Berlin, Germany ; Department of Psychiatry and Psychotherapy, Charité Berlin, Germany
Altenstein, Slawek; German Center for Neurodegenerative Diseases (DZNE), Berlin, Germany ; Department of Psychiatry and Psychotherapy, Charité Berlin, Germany
Schneider, Anja ; German Center for Neurodegenerative Diseases (DZNE), Bonn, Germany ; University of Bonn Medical Center, Department of Neurodegenerative Diseases and Geriatric Psychiatry, Bonn, Germany
Fliessbach, Klaus; German Center for Neurodegenerative Diseases (DZNE), Bonn, Germany ; University of Bonn Medical Center, Department of Neurodegenerative Diseases and Geriatric Psychiatry, Bonn, Germany
Wiltfang, Jens ; German Center for Neurodegenerative Diseases (DZNE), Goettingen, Germany ; Department of Psychiatry and Psychotherapy, University Medical Center Goettingen, University of Goettingen, Goettingen, Germany ; Neurosciences and Signaling Group, Institute of Biomedicine (iBiMED), Department of Medical Sciences, University of Aveiro, Aveiro, Portugal
Rostamzadeh, Ayda; German Center for Neurodegenerative Diseases (DZNE), Bonn, Germany
Glanz, Wenzel; German Center for Neurodegenerative Diseases (DZNE), Magdeburg, Germany
Teipel, Stefan; German Center for Neurodegenerative Diseases (DZNE), Rostock, Germany ; Department of Psychosomatic Medicine, Rostock University Medical Center, Rostock, Germany
Kilimann, Ingo; German Center for Neurodegenerative Diseases (DZNE), Rostock, Germany ; Department of Psychosomatic Medicine, Rostock University Medical Center, Rostock, Germany
Goerss, Doreen; German Center for Neurodegenerative Diseases (DZNE), Rostock, Germany ; Department of Psychosomatic Medicine, Rostock University Medical Center, Rostock, Germany
Laske, Christoph; German Center for Neurodegenerative Diseases (DZNE), Tuebingen, Germany ; Section for Dementia Research, Hertie Institute for Clinical Brain Research and Department of Psychiatry and Psychotherapy, University of Tuebingen, Tuebingen, Germany
Munk, Matthias H; German Center for Neurodegenerative Diseases (DZNE), Tuebingen, Germany ; Department of Psychiatry and Psychotherapy, University of Tuebingen, Tuebingen, Germany
Spottke, Annika; German Center for Neurodegenerative Diseases (DZNE), Bonn, Germany ; Department of Neurology, University of Bonn, Bonn, Germany
Roy, Nina; German Center for Neurodegenerative Diseases (DZNE), Bonn, Germany
HENEKA, Michael ; University of Luxembourg ; German Center for Neurodegenerative Diseases (DZNE), Bonn, Germany
Brosseron, Frederic ; German Center for Neurodegenerative Diseases (DZNE), Bonn, Germany
Wagner, Michael ; German Center for Neurodegenerative Diseases (DZNE), Bonn, Germany ; University of Bonn Medical Center, Department of Neurodegenerative Diseases and Geriatric Psychiatry, Bonn, Germany
Wolfsgruber, Steffen; German Center for Neurodegenerative Diseases (DZNE), Bonn, Germany ; University of Bonn Medical Center, Department of Neurodegenerative Diseases and Geriatric Psychiatry, Bonn, Germany
Dobisch, Laura; German Center for Neurodegenerative Diseases (DZNE), Magdeburg, Germany
Dechent, Peter; MR-Research in Neurosciences, Department of Cognitive Neurology, Georg-August-University Goettingen, Goettingen, Germany
Hetzer, Stefan; Berlin Center for Advanced Neuroimaging, Charité - Universitaetsmedizin Berlin, Berlin, Germany
Scheffler, Klaus; Department for Biomedical Magnetic Resonance, University of Tuebingen, Tuebingen, Germany
Zeidman, Peter ; Wellcome Centre for Human Neuroimaging, UCL Institute of Neurology, London, UK
Stern, Yaakov; Cognitive Neuroscience Division, Department of Neurology, Columbia University Vagelos College of Physicians and Surgeons, New York, NY, USA
Schott, Björn H ; German Center for Neurodegenerative Diseases (DZNE), Goettingen, Germany ; Department of Psychiatry and Psychotherapy, University Medical Center Goettingen, University of Goettingen, Goettingen, Germany ; Leibniz Institute for Neurobiology, Magdeburg, Germany
Jessen, Frank; German Center for Neurodegenerative Diseases (DZNE), Bonn, Germany ; Department of Psychiatry, University of Cologne, Koeln, Germany ; Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases (CECAD), University of Cologne, Koeln, Germany
Düzel, Emrah; German Center for Neurodegenerative Diseases (DZNE), Magdeburg, Germany ; Institute of Cognitive Neurology and Dementia Research (IKND), Otto-von-Guericke University, Magdeburg, Germany
Maass, Anne ; German Center for Neurodegenerative Diseases (DZNE), Magdeburg, Germany. Anne.Maass@dzne.de
Ziegler, Gabriel ; German Center for Neurodegenerative Diseases (DZNE), Magdeburg, Germany. Gabriel.Ziegler@dzne.de ; Institute of Cognitive Neurology and Dementia Research (IKND), Otto-von-Guericke University, Magdeburg, Germany. Gabriel.Ziegler@dzne.de
We thank the members of the DELCODE group in Magdeburg for providing helpful feedback and suggestions with respect to the conducted analyses. The study was funded by the German Center for Neurodegenerative Diseases (Deutsches Zentrum f\u00FCr Neurodegenerative Erkrankungen (DZNE)), reference number BN012. This work was supported by the UK Medical Research Council (grant number: MR/X020274/1 to P.Z.), the National Institute on Aging (R24 AG061421 to Y.S. and G.Z.), the federal state of Saxony-Anhalt and the European Regional Development Fund (ERDF) in the Center for Behavioral Brain Sciences (CBBS, ZS/2016/04/78113 to J.M.) and the German Research Foundation (DFG, Project-ID 425899996 to E.D., A.M. and G.Z.).
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