Background: Atherosclerosis is a major factor in cognitive decline among aging individuals and is frequently linked to the accumulation of white matter hyperintensities. Brain resilience, which represents the brain's capacity to withstand external disruptions, remains poorly understood in terms of how atherosclerosis impacts it and, in turn, influences cognition. Here, we investigated the relationship between atherosclerosis, white matter hyperintensities, and structural network resilience, along with their combined effects on cognitive performance.
Methods: We utilized data from the large-scale community cohort Polyvascular Evaluation for Cognitive Impairment and Vascular Events (n = 2160). Whole-brain structural connections were constructed, and structural disconnections were simulated based on white matter hyperintensities. SNR, serving as a marker to quantify structural network resilience, is defined by the similarity of hub nodes between the original network and its disconnected counterpart.
Results: SNR showed higher odds ratios compared to white matter hyperintensities in relation to arterial status. Additionally, chain mediation analysis indicated that cognitive decline associated with atherosclerosis was partially mediated by both white matter hyperintensities and structural network resilience. Atherosclerosis accelerates the degradation of brain structural network resilience as age increases.
Conclusions: These findings suggest that SNR could offer complementary insights into cognitive decline caused by atherosclerosis and serve as a potential biomarker of brain health in atherosclerotic conditions. Additionally, SNR may act as an indicator for guiding the selection of future therapies for atherosclerosis.
Keywords: Atherosclerosis; Cognition; Structural network resilience; White matter hyperintensities.
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