Entorhinal-hippocampal circuit integrity is related to mnemonic discrimination and amyloid-β pathology in older adults

Adams, J. N.; Kim, S.; Rizvi, B.; Sathishkumar, M.; Taylor, L.; Harris, A. L.; Mikhail, A.; Keator, D. B.; McMillan, L.; Yassa, M. A.

doi:10.1101/2022.05.10.491249

bioRxiv · 10.1101/2022.05.10.491249

Entorhinal-hippocampal circuit integrity is related to mnemonic discrimination and amyloid-β pathology in older adults

Adams, J. N.·Kim, S.·Rizvi, B.·Sathishkumar, M.·Taylor, L.·Harris, A. L.·Mikhail, A.·Keator, D. B.·McMillan, L.·Yassa, M. A.

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Abstract

Mnemonic discrimination, a cognitive process that relies on hippocampal pattern separation, is one of the first memory domains to decline in aging and preclinical Alzheimers disease. We tested if functional connectivity (FC) within the entorhinal-hippocampal circuit, measured with high-resolution resting state fMRI, is associated with mnemonic discrimination and A{beta} pathology, measured with PET, in nondemented older adults. Low object mnemonic discrimination performance was specifically associated with increased FC between anterolateral entorhinal cortex (alEC) and dentate gyrus (DG)/CA3, supporting the importance of this connection to object memory. This hyperconnectivity between alEC-DG/CA3 was related to A{beta} pathology and decreased entorhinal cortex volume. In contrast, spatial mnemonic discrimination was not associated with altered FC. A{beta} was further associated with decreased FC and volume within hippocampal subfields. Our findings suggest that A{beta} may indirectly lead to memory impairment through entorhinal-hippocampal circuit dysfunction and neurodegeneration, and provide a mechanism for vulnerability of object mnemonic discrimination.

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Adams, J. N., Kim, S., Rizvi, B., Sathishkumar, M., Taylor, L., Harris, A. L., Mikhail, A., Keator, D. B., McMillan, L., Yassa, M. A.. 2022-05-10. Entorhinal-hippocampal circuit integrity is related to mnemonic discrimination and amyloid-β pathology in older adults. https://doi.org/10.1101/2022.05.10.491249

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