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Rostral-middle locus coeruleus integrity and subjective cognitive decline in early old age

Published online by Cambridge University Press:  16 December 2022

Tyler Reed Bell*
Department of Psychiatry, University of California San Diego, San Diego, La Jolla, CA 92093, USA Center for Behavior Genetics of Aging, University of California, San Diego, La Jolla, CA 92093, USA
Jeremy A. Elman
Department of Psychiatry, University of California San Diego, San Diego, La Jolla, CA 92093, USA Center for Behavior Genetics of Aging, University of California, San Diego, La Jolla, CA 92093, USA
Asad Beck
Center for Neurotechnology, University of Washington, Seattle, WA, USA
Christine Fennema-Notestine
Department of Psychiatry, University of California San Diego, San Diego, La Jolla, CA 92093, USA Center for Behavior Genetics of Aging, University of California, San Diego, La Jolla, CA 92093, USA Department of Radiology, University of California San Diego, San Diego, La Jolla, CA 92093, USA
Daniel E. Gustavson
Institute for Behavioral Genetics, University of Colorado Boulder, Boulder, CO, USA
Donald J. Hagler
Department of Psychiatry, University of California San Diego, San Diego, La Jolla, CA 92093, USA Department of Radiology, University of California San Diego, San Diego, La Jolla, CA 92093, USA
Amy J. Jack
Department of Psychiatry, University of California San Diego, San Diego, La Jolla, CA 92093, USA Center for Behavior Genetics of Aging, University of California, San Diego, La Jolla, CA 92093, USA
Michael J. Lyons
Department of Psychology, Boston University, Boston, MA 02215, USA
Olivia K. Puckett
Department of Psychiatry, University of California San Diego, San Diego, La Jolla, CA 92093, USA Center for Behavior Genetics of Aging, University of California, San Diego, La Jolla, CA 92093, USA
Rosemary Toomey
Department of Psychology, Boston University, Boston, MA 02215, USA
Carol E. Franz
Department of Psychiatry, University of California San Diego, San Diego, La Jolla, CA 92093, USA Center for Behavior Genetics of Aging, University of California, San Diego, La Jolla, CA 92093, USA
William S. Kremen
Department of Psychiatry, University of California San Diego, San Diego, La Jolla, CA 92093, USA Center for Behavior Genetics of Aging, University of California, San Diego, La Jolla, CA 92093, USA
Corresponding author: Tyler Reed Bell, email:



Abnormal tau, a hallmark Alzheimer’s disease (AD) pathology, may appear in the locus coeruleus (LC) decades before AD symptom onset. Reports of subjective cognitive decline are also often present prior to formal diagnosis. Yet, the relationship between LC structural integrity and subjective cognitive decline has remained unexplored. Here, we aimed to explore these potential associations.


We examined 381 community-dwelling men (mean age = 67.58; SD = 2.62) in the Vietnam Era Twin Study of Aging who underwent LC-sensitive magnetic resonance imaging and completed the Everyday Cognition scale to measure subjective cognitive decline along with their selected informants. Mixed models examined the associations between rostral-middle and caudal LC integrity and subjective cognitive decline after adjusting for depressive symptoms, physical morbidities, and family. Models also adjusted for current objective cognitive performance and objective cognitive decline to explore attenuation.


For participant ratings, lower rostral-middle LC contrast to noise ratio (LCCNR) was associated with significantly greater subjective decline in memory, executive function, and visuospatial abilities. For informant ratings, lower rostral-middle LCCNR was associated with significantly greater subjective decline in memory only. Associations remained after adjusting for current objective cognition and objective cognitive decline in respective domains.


Lower rostral-middle LC integrity is associated with greater subjective cognitive decline. Although not explained by objective cognitive performance, such a relationship may explain increased AD risk in people with subjective cognitive decline as the LC is an important neural substrate important for higher order cognitive processing, attention, and arousal and one of the first sites of AD pathology.

Research Article
Copyright © INS. Published by Cambridge University Press, 2022

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Carol E. Franz and William S. Kremen are joint senior authors


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