HAI Book 2025 - Flipbook - Page 692
Heinrich, Lukas
171
Locus coeruleus - medial temporal lobe functional connectivity
confers protection against amyloid-related cognitive decline in the context
of high cognitive reserve
Lukas Heinrich1,3, Prokopis C Prokopiou1, Emma E Wiklund1, Kathryn V Papp4, Dorene M
Rentz2,4, Reisa A Sperling2,4, Keith A Johnson1,2,4, Heidi IL Jacobs1
1
Department of Radiology, Massachusetts General Hospital / Harvard Medical SChool, Boston, MA, US
Department of Neurology, Massachusetts General Hospital/ Harvard Medical School, Boston, MA, US
3
Faculty of Health, Medicine and Life Sciences, Maastricht University, Maastricht, NL
4
Center for Alzheimer Research and Treatment, Department of Neurology, Brigham and Women’s Hospital, Boston,
MA, US
2
Background: Research into cognitive reserve (CR) has indicated that its preserving effect may involve changes in
cortical network connectivity. The noradrenergic locus coeruleus (LC), one of the first brain areas affected by
Alzheimer9s pathology, recruits networks necessary to meet a given task9s demands. We showed previously that
better LC structure attenuates tau-related cognitive decline in individuals with high CR. Now, we investigated the
impact of functional connectivity between the LC and resilience-relevant regions, and cognitive reserve, on betaamyloid-related cognitive decline.
Methods: Older individuals (N=128) that underwent fMRI and 11C-Pittsburgh Compound-B (PiB) PET were selected
from the Harvard Aging Brain Study (Figure 1). Functional connectivity (FC) between LC and ROIs previously shown
to confer resilience was obtained from a novelty-versus-repetition Face-Name memory task using generalized
psychophysiological interaction analysis. Cognition over time was assessed using PACC5. A CR composite score
was constructed by averaging z-scored verbal-IQ, years of education, and Hollingshead scale. Cluster analysis
grouped individuals based on cognitive reserve and PiB burden. (Non)linear mixed-effects models tested whether
the association between LC-ROI FC and cognitive trajectories differed across groups.
Results: Higher CR related to better baseline PACC-scores (p
