@article{45ba902a839141c182f754c5da2f82d6,
title = "Lower novelty-related locus coeruleus function is associated with A beta-related cognitive decline in clinically healthy individuals",
abstract = "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.",
keywords = "AMYLOID-BETA, NETWORK, BRAIN, CONNECTIVITY, TAU, DEPOSITION, DEMENTIA, NEURONS, MEMORY, ADULTS",
author = "P.C. Prokopiou and N. Engels-Dominguez and K.V. Papp and M.R. Scott and A.P. Schultz and C. Schneider and M.E. Farrell and R.F. Buckley and Y.T. Quiroz and {El Fakhri}, G. and D.M. Rentz and R.A. Sperling and K.A. Johnson and H.I.L. Jacobs",
note = "Funding Information: We would like to thank all the participants of the Harvard Aging Brain Study. This work was supported in part by the Gordon Center for Medical Imaging P41 EB022544 and the Athinoula A. Martinos Center for Biomedical Imaging P41 EEB015896, as well as shared instrumentation grants: S10OD018035, S10RR021110, S10OD010364, S10RR023401, S10RR023043, and 1S10RR019307. This research was supported by the Harvard Aging Brain Study P01 AG036694 (MPIs Reisa Sperling, MD and Keith Johnson, MD), NIH grant R01 AG046396 (PI Keith Johnson, MD), NIH grant T32 EB013180 (PI El Fakhri Georges, PhD), NIH grant R01AG062559 and R01AG068062 (PI Heidi Jacobs, PhD) and Dekker-Padget Dutch2USA Grant (Nina Engels-Dom{\'i}nguez). Funding Information: P.C.P. and N.E.D. aided in study design, performed methods development, analyzed imaging data, performed statistical analyses, interpreted data, and wrote the manuscript. K.V.P. and D.M.R. aided in data collection, neuropsychological assessments, interpreted the results and reviewed the manuscript. N.E.D. and M.R.S. aided in data collection, study organization and data management. C.S. aided in methods development, interpreted the data and reviewed the manuscript. M.R.S., A.P.S., R.F.B. aided in MRI methods, data management and reviewed the manuscript. M.E.F and G.E.F. aided in PET methods, interpreted the results, and revised the manuscript. Y.T.Q. interpreted the results and revised the manuscript. R.A.S. and K.A.J. provided the participants, data analytic tools, aided in study design, interpreted results, and revised the manuscript. H.I.L.J., D.M.R., G.E.F, R.A.S., and K.A.J. acquired the financial support for the project leading to this publication. H.I.L.J. conceptualized this study, aided in study design, aided in methods development, aided in statistical analyses, interpreted data, revised the manuscript, and had the general supervision of the study. Publisher Copyright: {\textcopyright} 2022, The Author(s).",
year = "2022",
month = mar,
day = "23",
doi = "10.1038/s41467-022-28986-2",
language = "English",
volume = "13",
journal = "Nature Communications",
issn = "2041-1723",
publisher = "Nature Publishing Group",
number = "1",
}