Differences in LC integrity and fMRI activations in healthy aging and MCI associated with successful memory encoding

Penalba - Sanchez, L.; Yi, Y.-J.; Kurt, E.; Feminella, G. D.; Loane, C.; Duckett, M.; Weiskopf, N.; Callaghan, M. F.; Dolan, R. J.; Howard, R. J.; Duezel, E.; Haemmerer, D.

doi:10.1101/2025.08.29.672869

bioRxiv · 10.1101/2025.08.29.672869

Differences in LC integrity and fMRI activations in healthy aging and MCI associated with successful memory encoding

Penalba - Sanchez, L.·Yi, Y.-J.·Kurt, E.·Feminella, G. D.·Loane, C.·Duckett, M.·Weiskopf, N.·Callaghan, M. F.·Dolan, R. J.·Howard, R. J.·Duezel, E.·Haemmerer, D.

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Abstract

INTRODUCTIONWe examined whether the decline of delayed episodic memory in old age and MCI is related to structural integrity of the locus coeruleus (LC). We also tested whether LC integrity was associated with encoding-related brain activity, controlling for emotional salience. METHODSParticipants (28 young adults, 28 older adults, 25 MCI) memorized emotional and neutral images during fMRI. Delayed memory was tested four hours later and compared to immediate memory. LC integrity was measured with a neuromelanin-sensitive sequence. RESULTSMCI showed overall memory decline, independent of delay or emotional valence, and reduced LC integrity compared to older adults. Across participants, LC integrity correlated with delayed memory, but did not explain performance within OA or MCI. LC integrity was associated with lower activity related to encoding success and emotional salience. Groups remembered emotional better than neutral images, though memory was greatly impaired in MCI, matching with their reduce LC integrity. DISCUSSIONLC integrity was associated with lower brain activity during encoding and emotional salience processing, no clear relationship with delayed memory performance was observed in MCI.

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Penalba - Sanchez, L., Yi, Y.-J., Kurt, E., Feminella, G. D., Loane, C., Duckett, M., Weiskopf, N., Callaghan, M. F., Dolan, R. J., Howard, R. J., Duezel, E., Haemmerer, D.. 2025-09-01. Differences in LC integrity and fMRI activations in healthy aging and MCI associated with successful memory encoding. https://doi.org/10.1101/2025.08.29.672869

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