HAI Book 2025 - Flipbook - Page 567
Wiklund, Emma E
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Lower locus coeruleus metabolism is associated with greater yearto-year intraindividual cognitive variability in older individuals with elevated
levels of Alzheimer9s disease pathology
Emma E Wiklund1, Maxime Van Egroo1,2, Elouise A Koops1, Bernard J Hanseeuw3,4, Kathryn V
Papp7, Dorene M Rentz6,7, Reisa A Sperling6,7, Keith A Johnson3,6,7, Heidi IL Jacobs1
1
The Athinoula A. Martinos Center for Biomedical Imaging, Department of Radiology, Massachusetts General
Hospital, Harvard Medical School, Boston, MA, US
2
Faculty of Health, Medicine and Life Sciences, Mental Health and Neuroscience Research Institute, Alzheimer
Centre Limburg, Maastricht University, Maastricht, NL
3
Gordon Center for Medical Imaging, Department of Radiology, Massachusetts General Hospital, Harvard Medical
School, Boston, MA, US
4
Department of Neurology, Institute of Neuroscience, Cliniques Universitaires SaintLuc, Université Catholique de
Louvain, Brussels, BE
5
Department of Neurology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, US
6
Center for Alzheimer Research and Treatment, Department of Neurology, Brigham and Women’s Hospital, Boston,
MA, US
Introduction: Intraindividual variability in cognitive performance is associated with increased risk for Alzheimer9s
disease (AD) and has been linked to the structure and function of catecholaminergic systems, including the
noradrenergic locus coeruleus (LC). Importantly, higher LC metabolism was demonstrated to provide resilience
against cognitive decline in preclinical AD. Here, we examined the association between LC metabolism and yearto-year intraindividual variability and assessed the moderating effect of AD pathology on this relationship.
Methods: 155 participants from the Harvard Aging Brain Study (Figure 1) underwent structural MRI,
Fluorodeoxyglucose (FDG)-, Flortaucipir (FTP)-, Pittsburgh compound B (PiB)-PET scans, and longitudinal
cognitive evaluation (mean follow-up 7.74+/-2.34 years). LC FDG-PET signal was extracted using an in-house MRIbased joint-entropy deblurring algorithm with reference to cerebellar white. Year-to-year intraindividual cognitive
variability was defined by the coefficient of variation (CoV; SD/mean) within each person for several cognitive
tests (Figure 2). Entorhinal FTP and neocortical PiB-PET were partial-volume corrected. Multiple linear
regressions adjusted for age, sex, and education associated the CoV for each cognitive test with i) LC FDG-PET
signal and ii) LC FDG-PET signal interacted with entorhinal FTP-PET or neocortical PiB.
Results: LC FDG-PET signal was not associated with CoV on any cognitive tests (Figure 2). Interaction models
indicated that lower LC FDG-PET signal was associated with higher CoV on the DSST (p=0.02) and LM (p=0.02) in
individuals with elevated FTP-PET, and higher LM CoV in those with elevated neocortical PiB (p=0.04). Excluding
participants with a CDR>0 (N=15) at the time of the FDG-PET did not affect the FTP (DSST: p=0.002, LM: p=0.02) or
PiB results (DSST: p=0.03, LM: p=0.02) (Figure 3).
Conclusion: Our findings suggest that higher LC metabolism contributes to more stable longitudinal cognitive
performance in individuals with elevated AD pathology. These findings therefore have implications for the early
detection of individuals at risk for AD trajectories.
HAI2025 - 567
