Hippocampal activation is associated with longitudinal amyloid accumulation and cognitive decline

Leal, Stephanie L.; Landau, Susan M.; Bell, Rachel K.; Jagust, William J.

doi:10.7554/eLife.22978

Hippocampal activation is associated with longitudinal amyloid accumulation and cognitive decline

Journal Article · Wed Feb 08 00:00:00 EST 2017 · eLife

DOI:https://doi.org/10.7554/eLife.22978· OSTI ID:1379725

^[1]; Landau, Susan M. ^[2]; Bell, Rachel K. ^[1]; Jagust, William J. ^[2]

Univ. of California, Berkeley, CA (United States)
Univ. of California, Berkeley, CA (United States); Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States)

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.

View Accepted Manuscript (DOE)

Research Organization:: Lawrence Berkeley National Laboratory (LBNL), Berkeley, CA (United States)

Sponsoring Organization:: National Institutes of Health; USDOE

Grant/Contract Number:: AC02-05CH11231

OSTI ID:: 1379725

Journal Information:: eLife, Journal Name: eLife Vol. 6; ISSN 2050-084X

Publisher:: eLife Sciences Publications, Ltd.Copyright Statement

Country of Publication:: United States

Language:: English

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