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.

Details

Title
Lower novelty-related locus coeruleus function is associated with Aβ-related cognitive decline in clinically healthy individuals
Author
Prokopiou, Prokopis C 1   VIAFID ORCID Logo  ; Engels-Domínguez, Nina 2   VIAFID ORCID Logo  ; Papp, Kathryn V 3 ; Scott, Matthew R 4 ; Schultz, Aaron P 5 ; Schneider, Christoph 1 ; Farrell, Michelle E 6 ; Buckley, Rachel F 7   VIAFID ORCID Logo  ; Quiroz, Yakeel T 8   VIAFID ORCID Logo  ; El Fakhri Georges 1 ; Rentz, Dorene M 3 ; Sperling, Reisa A 3 ; Johnson, Keith A 9 ; Jacobs Heidi I L 2   VIAFID ORCID Logo 

1  Massachusetts General Hospital, Harvard Medical School, Gordon Center for Medical Imaging, Department of Radiology, Boston, USA (GRID:grid.32224.35) (ISNI:0000 0004 0386 9924) 
2  Massachusetts General Hospital, Harvard Medical School, Gordon Center for Medical Imaging, Department of Radiology, Boston, USA (GRID:grid.32224.35) (ISNI:0000 0004 0386 9924); Maastricht University, Faculty of Health, Medicine and Life Sciences, School for Mental Health and Neuroscience, Alzheimer Centre Limburg, Maastricht, The Netherlands (GRID:grid.5012.6) (ISNI:0000 0001 0481 6099) 
3  Brigham and Women’s Hospital, Harvard Medical School, Center for Alzheimer Research and Treatment, Department of Neurology, Boston, USA (GRID:grid.62560.37) (ISNI:0000 0004 0378 8294); Massachusetts General Hospital, Harvard Medical School, Department of Neurology, Boston, USA (GRID:grid.32224.35) (ISNI:0000 0004 0386 9924) 
4  Massachusetts General Hospital, Harvard Medical School, Department of Neurology, Boston, USA (GRID:grid.32224.35) (ISNI:0000 0004 0386 9924); Boston University, Department of Biostatistics, Boston, USA (GRID:grid.189504.1) (ISNI:0000 0004 1936 7558) 
5  Massachusetts General Hospital, Harvard Medical School, Department of Neurology, Boston, USA (GRID:grid.32224.35) (ISNI:0000 0004 0386 9924); Massachusetts General Hospital, Harvard Medical School, The Athinoula A. Martinos Center for Biomedical Imaging, Department of Radiology, Boston, USA (GRID:grid.32224.35) (ISNI:0000 0004 0386 9924) 
6  Massachusetts General Hospital, Harvard Medical School, Department of Neurology, Boston, USA (GRID:grid.32224.35) (ISNI:0000 0004 0386 9924) 
7  Brigham and Women’s Hospital, Harvard Medical School, Center for Alzheimer Research and Treatment, Department of Neurology, Boston, USA (GRID:grid.62560.37) (ISNI:0000 0004 0378 8294); Massachusetts General Hospital, Harvard Medical School, Department of Neurology, Boston, USA (GRID:grid.32224.35) (ISNI:0000 0004 0386 9924); University of Melbourne, Melbourne School of Psychological Sciences, Parkville, Australia (GRID:grid.1008.9) (ISNI:0000 0001 2179 088X) 
8  Massachusetts General Hospital, Harvard Medical School, Department of Neurology, Boston, USA (GRID:grid.32224.35) (ISNI:0000 0004 0386 9924); Massachusetts General Hospital, Harvard Medical School, Department of Psychiatry, Boston, USA (GRID:grid.32224.35) (ISNI:0000 0004 0386 9924) 
9  Massachusetts General Hospital, Harvard Medical School, Gordon Center for Medical Imaging, Department of Radiology, Boston, USA (GRID:grid.32224.35) (ISNI:0000 0004 0386 9924); Brigham and Women’s Hospital, Harvard Medical School, Center for Alzheimer Research and Treatment, Department of Neurology, Boston, USA (GRID:grid.62560.37) (ISNI:0000 0004 0378 8294); Massachusetts General Hospital, Harvard Medical School, Department of Neurology, Boston, USA (GRID:grid.32224.35) (ISNI:0000 0004 0386 9924) 
Publication year
2022
Publication date
2022
Publisher
Nature Publishing Group
e-ISSN
20411723
Source type
Scholarly Journal
Language of publication
English
DOI
https://doi.org/10.1038/s41467-022-28986-2
ProQuest document ID
2642177256
Copyright
© The Author(s) 2022. This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.