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| Home > Publications Database > Dysfunction of the episodic memory network in the Alzheimer's disease cascade. |
| Home > Publications Database > Dysfunction of the episodic memory network in the Alzheimer's disease cascade. |
| Journal Article | DZNE-2026-00412 |
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2026
Springer Nature
[London]
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Please use a persistent id in citations: doi:10.1038/s41467-026-71831-z
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.
Keyword(s): Alzheimer Disease: physiopathology (MeSH) ; Alzheimer Disease: diagnostic imaging (MeSH) ; Alzheimer Disease: metabolism (MeSH) ; Humans (MeSH) ; Memory, Episodic (MeSH) ; Magnetic Resonance Imaging (MeSH) ; Male (MeSH) ; Female (MeSH) ; Aged (MeSH) ; Disease Progression (MeSH) ; Cognitive Dysfunction: physiopathology (MeSH) ; Cognitive Dysfunction: diagnostic imaging (MeSH) ; Longitudinal Studies (MeSH) ; Brain: physiopathology (MeSH) ; Brain: diagnostic imaging (MeSH) ; tau Proteins: metabolism (MeSH) ; Aged, 80 and over (MeSH) ; Biomarkers: metabolism (MeSH) ; Middle Aged (MeSH) ; Cognition (MeSH) ; Nerve Net: physiopathology (MeSH) ; Nerve Net: diagnostic imaging (MeSH) ; Amyloid beta-Peptides: metabolism (MeSH) ; tau Proteins ; Biomarkers ; Amyloid beta-Peptides
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