Cognitive reserve against Alzheimer’s pathology is linked to brain activity during memory formation
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.
Authors
- Emrah Düzel (ORCID: https://orcid.org/0000-0002-0139-5388)
- Jens Wiltfang (ORCID: https://orcid.org/0000-0003-1492-5330)
- Hartmut Schütze
- Ayda Rostamzadeh (ORCID: https://orcid.org/0000-0001-5189-134X)
- Lukas Preis (ORCID: https://orcid.org/0000-0001-7601-6410)
- Annika Spottke (ORCID: https://orcid.org/0000-0001-9854-2972)
- Nina Roy
- Oliver Peters (ORCID: https://orcid.org/0000-0003-0568-2998)
- Stefan Johannes Teipel (ORCID: https://orcid.org/0000-0002-3586-3194)
- Gabriel Ziegler (ORCID: https://orcid.org/0000-0001-6589-6416)
- Frederic Brosseron (ORCID: https://orcid.org/0000-0003-3137-7516)
- Anne Maaß (ORCID: https://orcid.org/0000-0002-7889-795X)
- Niklas Vockert (ORCID: https://orcid.org/0000-0001-5915-2517)
- Yaakov Stern (ORCID: https://orcid.org/0000-0001-7542-3241)
- Klaus Scheffler (ORCID: https://orcid.org/0000-0001-6316-8773)
- Laura Dobisch
- Renat Yakupov (ORCID: https://orcid.org/0000-0002-3868-284X)
- Luca Kleineidam (ORCID: https://orcid.org/0009-0006-3309-6856)
- José Bernal (ORCID: https://orcid.org/0000-0003-3167-5134)
- Daria Gref
- Michael Wagner (ORCID: https://orcid.org/0000-0003-2589-6440)
- Aditya Nemali (ORCID: https://orcid.org/0000-0003-4993-6291)
- Peter Zeidman (ORCID: https://orcid.org/0000-0003-3610-6619)
- Klaus Fließbach (ORCID: https://orcid.org/0000-0002-0183-7510)
- Enise I. Incesoy (ORCID: https://orcid.org/0000-0003-2014-4098)
- Josef Priller (ORCID: https://orcid.org/0000-0001-7596-0979)
- Steffen Wolfsgruber (ORCID: https://orcid.org/0000-0002-3962-3219)
- Judith Machts
- Frank Jessen (ORCID: https://orcid.org/0000-0003-1067-2102)
- Stefan Hetzer (ORCID: https://orcid.org/0000-0002-1773-1518)
- Ingo Kilimann (ORCID: https://orcid.org/0000-0002-3269-4452)
- Anja Schneider (ORCID: https://orcid.org/0000-0001-9540-8700)
- Michael T. Heneka (ORCID: https://orcid.org/0000-0003-4996-1630)
- Slawek Altenstein (ORCID: https://orcid.org/0000-0003-2753-5999)
- Luisa‐Sophie Schneider (ORCID: https://orcid.org/0000-0001-5822-1744)
- Wenzel Glanz (ORCID: https://orcid.org/0000-0002-5865-4176)
- Matthias H. Munk (ORCID: https://orcid.org/0000-0002-5339-4045)
- Björn H. Schott (ORCID: https://orcid.org/0000-0002-8237-4481)
- Peter Dechent (ORCID: https://orcid.org/0009-0006-4005-3352)
- Eike Jakob Spruth
- Christoph Laske
- Doreen Göerß
Institutions
- TH Köln - University of Applied Sciences (DE)
- University of Bonn (DE)
- Wellcome Centre for Human Neuroimaging (GB)
- University of Cologne (DE)
- University of Luxembourg (LU)
- German Center for Neurodegenerative Diseases (DE)
- Humboldt-Universität zu Berlin (DE)
- UK Dementia Research Institute (GB)
- Cologne Excellence Cluster on Cellular Stress Responses in Aging Associated Diseases (DE)
- University Hospital Magdeburg (DE)
- Hertie Institute for Clinical Brain Research (DE)
- University College London (GB)
- University of Rostock (DE)
- University of Aveiro (PT)
- Technical University of Munich (DE)
- University of Göttingen (DE)
- Columbia University (US)
- Charité - Universitätsmedizin Berlin (DE)
- University of Tübingen (DE)
- Otto-von-Guericke-Universität Magdeburg (DE)
- Leibniz Institute for Neurobiology (DE)
- University of Edinburgh (GB)
Publication Details
- Journal
- Nature Communications
- Published
- 2024-11-13
- DOI
- https://doi.org/10.1038/s41467-024-53360-9
- Citations
- 29
- Primary Topic
- Functional Brain Connectivity Studies
- Type
- article
- Field-Weighted Citation Impact
- 9.94
Funders
- Eli Lilly and Company
- Pfizer
- Biogen
- Arcadia Fund
- Center for Behavioral Brain Sciences
- Deutsche Forschungsgemeinschaft
- Eisai
- Deutsches Zentrum für Neurodegenerative Erkrankungen
- Medical Research Council
- European Regional Development Fund