Dysfunction of the episodic memory network in the Alzheimer’s disease cascade
Abstract
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.
Article Details
Authors (44)
René Lattmann
Niklas Vockert
Jose Bernal
Judith Wesenberg
Yanin Suksangkharn
Renat Yakupov
Hartmut Schütze
Wenzel Glanz
Enise Incesoy
Michaela Butryn
Falk Lüsebrink
Matthias Schmid
Melina Stark
Luca Kleineidam
Annika Spottke
Marie Coenjaerts
Frederic Brosseron
Klaus Fliessbach
Anja Schneider
Peter Dechent
Klaus Scheffler
Stefan Hetzer
Alfredo Ramirez
Christoph Laske
Sebastian Sodenkamp
Slawek Altenstein
Luisa-Sophie Schneider
Daria Gref
Eike Jakob Spruth
Andrea Lohse
Björn H. Schott
Jens Wiltfang
Ingo Kilimann
Doreen Goerss
Ayda Rostamzadeh
Josef Priller
Oliver Peters
Julian Hellmann-Regen
Stefan Teipel
Michael Wagner
Frank Jessen
Anne Maass
Gabriel Ziegler
Emrah Düzel