Hippocampal activation is associated with longitudinal amyloid accumulation and cognitive decline.
The amyloid hypothesis suggests that beta-amyloid (Aβ) deposition leads to alterations in neural function and ultimately to cognitive decline in Alzheimer's disease. However, factors that underlie Aβ deposition are incompletely understood. One proposed model suggests that synaptic activity leads to increased Aβ deposition. More specifically, hyperactivity in the hippocampus may be detrimental and could be one factor that drives Aβ deposition. To test this model, we examined the relationship between hippocampal activity during a memory task using fMRI and subsequent longitudinal change in Aβ using PIB-PET imaging in cognitively normal older adults. We found that greater hippocampal activation at baseline was associated with increased Aβ accumulation. Furthermore, increasing Aβ accumulation mediated the influence of hippocampal activation on declining memory performance, demonstrating a crucial role of Aβ in linking hippocampal activation and memory. These findings support a model linking increased hippocampal activation to subsequent Aβ deposition and cognitive decline.
Helen Wills Neuroscience Institute, University of California, Berkeley, United States.
Stephanie L
0000-0002-8082-8291
SL
Leal
Helen Wills Neuroscience Institute, University of California, Berkeley, United States.|Molecular Biophysics and Integrated Bioimaging, Lawrence Berkeley National Laboratory, Berkeley, United States.
Susan M
SM
Landau
Helen Wills Neuroscience Institute, University of California, Berkeley, United States.
Rachel K
RK
Bell
Helen Wills Neuroscience Institute, University of California, Berkeley, United States.|Molecular Biophysics and Integrated Bioimaging, Lawrence Berkeley National Laboratory, Berkeley, United States.
William J
WJ
Jagust
D000368:Aged; D000369:Aged, 80 and over; D016229:Amyloid beta-Peptides / Q000378:metabolism*; D060825:Cognitive Dysfunction; D005260:Female; D006624:Hippocampus / Q000502:physiology*; D006801:Humans; D008137:Longitudinal Studies; D008279:Magnetic Resonance Imaging; D008297:Male; D049268:Positron-Emission Tomography
D016229:Amyloid beta-Peptides
PIB; aging; amyloid; hippocampus; human; longitudinal; memory; neuroscience