Lower novelty-related locus coeruleus function is associated with A beta-related cognitive decline in clinically healthy individuals

P.C. Prokopiou, N. Engels-Dominguez, K.V. Papp, M.R. Scott, A.P. Schultz, C. Schneider, M.E. Farrell, R.F. Buckley, Y.T. Quiroz, G. El Fakhri, D.M. Rentz, R.A. Sperling, K.A. Johnson, H.I.L. Jacobs*

*Corresponding author for this work

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Animal and human imaging research reported that the presence of cortical Alzheimer's Disease's (AD) neuropathology, beta-amyloid and neurofibrillary tau, is associated with altered neuronal activity and circuitry failure, together facilitating clinical progression. The locus coeruleus (LC), one of the initial subcortical regions harboring pretangle hyperphosphorylated tau, has widespread connections to the cortex modulating cognition. Here we investigate whether LC's in-vivo neuronal activity and functional connectivity (FC) are associated with cognitive decline in conjunction with beta-amyloid. We combined functional MRI of a novel versus repeated face-name paradigm, beta-amyloid-PET and longitudinal cognitive data of 128 cognitively unimpaired older individuals. We show that LC activity and LC-FC with amygdala and hippocampus was higher during novelty. We also demonstrated that lower novelty-related LC activity and LC-FC with hippocampus and parahippocampus were associated with steeper beta-amyloid-related cognitive decline. Our results demonstrate the potential of LC's functional properties as a gauge to identify individuals at-risk for AD-related cognitive decline.Older individuals exhibiting diminished function of the locus coeruleus while learning new information show faster cognitive decline that is typical for Alzheimer's disease.
Original languageEnglish
Article number1571
Number of pages14
JournalNature Communications
Issue number1
Publication statusPublished - 23 Mar 2022


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