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| Item Type: | Article |
|---|---|
| Title: | Dysfunction of the episodic memory network in the Alzheimer's disease cascade |
| Creators Name: | Lattmann, René, Vockert, Niklas, Bernal, Jose, Wesenberg, Judith, Suksangkharn, Yanin, Yakupov, Renat, Schütze, Hartmut, Glanz, Wenzel, Incesoy, Enise, Butryn, Michaela, Lüsebrink, Falk, Schmid, Matthias, Stark, Melina, Kleineidam, Luca, Spottke, Annika, Coenjaerts, Marie, Brosseron, Frederic, Fliessbach, Klaus, Schneider, Anja, Dechent, Peter, Scheffler, Klaus, Hetzer, Stefan, Ramirez, Alfredo, Laske, Christoph, Sodenkamp, Sebastian, Altenstein, Slawek, Schneider, Luisa-Sophie, Gref, Daria, Spruth, Eike Jakob, Lohse, Andrea, Schott, Björn H., Wiltfang, Jens, Kilimann, Ingo, Goerss, Doreen, Rostamzadeh, Ayda, Priller, Josef, Peters, Oliver, Hellmann-Regen, Julian, Teipel, Stefan, Wagner, Michael, Jessen, Frank, Maass, Anne, Ziegler, Gabriel and Düzel, Emrah |
| Abstract: | Alzheimer’s disease (AD) is a major cause of dementia and cognitive decline. Here, we assessed how episodic memory (EM) network dysfunction, a hallmark of AD, is related to the longitudinal progression of AD biomarkers, neurodegeneration and cognition using data from the DZNE DELCODE study. This data set includes over 1000 longitudinal functional magnetic resonance imaging measurements of EM network function. We related activation and deactivation of EM to individual disease progression scores from a disease progression model. Voxel-wise analyses revealed widespread loss of deactivation and activation with disease progression. Trajectories for the loss of deactivation were nonlinear, associated with amyloid- and tau-positivity and visually preceded trajectories of cognitive decline. The relationship between deactivation and cognitive decline was partly independent of neurodegeneration. Our results provide evidence that synaptic dysfunction and neurodegeneration are independent drivers of cognitive decline, providing a rationale for targeting synaptic dysfunction along the AD cascade. |
| Keywords: | Alzheimer Disease, Amyloid Beta-Peptides, Biomarkers, Brain, Cognition, Cognitive Dysfunction, Disease Progression, Episodic Memory, Longitudinal Studies, Magnetic Resonance Imaging, Nerve Net, Tau Proteins |
| Source: | Nature Communications |
| ISSN: | 2041-1723 |
| Publisher: | Nature Publishing Group |
| Volume: | 17 |
| Number: | 1 |
| Page Range: | 3578 |
| Date: | 17 April 2026 |
| Official Publication: | https://doi.org/10.1038/s41467-026-71831-z |
| PubMed: | View item in PubMed |
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