Hippocampal activation is associated with longitudinal amyloid accumulation and cognitive decline
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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.
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Greater hippocampal activation during encoding tasks predicts future cognitive decline in cognitively healthy elderly.
“and even predicts future cognitive decline in cognitively healthy elderly [178].”
From Apolipoprotein E4, inhibitory network dysfunction, and Alzheimer’s disease (2019) · cites this paper as [178]
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- Authors
- Leal, S. L., Landau, S. M., Bell, R. K., & Jagust, W. J.
- Affiliations
- University of California, Berkeley (US)
- Lawrence Berkeley National Laboratory (US)
- Corresponding author
- Leal, Stephanie L
- Jagust, William J
- Venue
- eLife
- Publisher
- eLife Sciences Publications, Ltd
- Published
- 2017-02-08
- Volume
- 6
- ISSN
- 2050-084X (ISSN-L)
- PMC
- PMC5325620
- OpenAlex
- W2586682108
- Cited by
- 117
- References
- 48
- Citations by year
- 2026: 5 · 2025: 10 · 2024: 11 · 2023: 16 · 2022: 11 · 2021: 16 · 2020: 14 · 2019: 20 · 2018: 10 · 2017: 4
- FWCI
- 10.79
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- eLife (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- eScholarship (California Digital Library) (submittedVersion)
- OSTI OAI (U.S. Department of Energy Office of Scientific and Technical Information) (submittedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- National Institute on Aging (AG054116, AG034570)
- Topics
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Cancer-related cognitive impairment studies
- Keywords
- hippocampal activation, amyloid-beta deposition, cognitive decline, Alzheimer's disease, amyloid hypothesis, memory performance, PiB PET, functional MRI, older adults, synaptic activity, longitudinal change
- MeSH terms
- Aged, Aged, 80 and over, Female, Hippocampus, Humans, Longitudinal Studies, Magnetic Resonance Imaging, Male, Amyloid beta-Peptides, Positron-Emission Tomography, Cognitive Dysfunction
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