Author(s): FOURTEAU, M., GRENIER, H., MESCAM, M., VAYSSIÈRE, N., GUYONNET, S., PAYOUX, P., BERRY, I., REMY, F., Institution: UNIVERSITY OF TOULOUSE, Country: FRANCE, Abstract-ID: 2120

INTRODUCTION:
Physical activity is a major modulator of healthy aging and is associated with reduced risk of cognitive decline. Regular physical activity has been shown to influence brain structure and function, including increased hippocampal volume and better episodic memory performance. In Alzheimer’s disease, one of the earliest sites of tau pathology is the locus coeruleus (LC), a small brainstem nucleus and the main source of cerebral noradrenaline, critically involved in cognitive processes, such as episodic memory and executive functions, and in motor function. LC integrity is also modulated by cognitive reserve, which includes physical activity as a protective factor against age-related decline. LC integrity can be assessed in vivo using neuromelanin-sensitive MRI, and previous work suggests that higher cardiorespiratory fitness is associated with better preservation of LC integrity.
The present study aimed to (1) assess LC integrity using neuromelanin-sensitive MRI, (2) characterize functional connectivity alterations associated with reduced LC integrity, and (3) explore the relationships between physical activity, cognitive reserve, and LC integrity and connectivity, using self-reported measures.
METHODS:
The study included 101 cognitively healthy older adults aged 72.2(±7.1) years. MRI included NM-sensitive T1-weighted and resting-state functional sequences. Physical activity was measured using the International Physical Activity Questionnaire (IPAQ), and cognitive reserve was assessed with the Lifetime of Experiences Questionnaire (LEQ), providing scores for different life periods and a total score. Participants were clustered into two cognitive reserve groups (low reserve (LR), aged 73.22 years, and high reserve (HR), aged 71.9 years, p>0.05; LR mean LEQ = 46.4, HR mean LEQ = 64.4, p<0.01), based on LEQ scores. Physical activity is considered one component of lifetime cognitive reserve, along with education, occupational, and leisure activities.
RESULTS:
Analysis confirmed that reduced LC integrity was associated with decreased functional connectivity between the LC and temporal (including hippocampus) and frontal regions (puncorr=0.01, threshold=200 voxels). No significant differences in LC contrast ratio were observed between cognitive reserve groups (p=0.3). However, participants with high cognitive reserve showed greater LC-hippocampal connectivity than those with low cognitive reserve (puncorr=0.001, threshold = 100 voxels), suggesting relative functional preservation of the hippocampus in the high-reserve group.
CONCLUSION:
These findings indicate that age-related LC alterations initially affect neural networks supporting memory and executive functions, while lifetime activities, including physical activity, do not significantly relate to LC structural integrity but may support functional compensation in affected regions. This study highlights the noradrenergic system as a neural substrate linking cognitive reserve including physical activity, and brain health in aging.