Association Between Carotid Plaque and Alzheimer's Disease Cerebrospinal Fluid Biomarkers and Cognitive Function in Cognitively Intact Adults: The CABLE Study

Background: The association between carotid plaque and cognitive decline has recently been reported. However, the current research evidence is insufficient, and the possible causes of cognitive changes are unknown. Objective: This study aims to explore the relationships between carotid plaque and cognition functions, cerebrospinal fluid (CSF) Alzheimer's disease (AD) biomarkers in cognitively intact adults, and try to study the underlying mechanisms. Methods: We enrolled 165 cognitively normal participants from the Chinese Alzheimer's Biomarker and LifestylE (CABLE) study, who had CSF AD biomarker measurements and carotid ultrasound. Linear modeling was used to assess the association of carotid plaque with CSF biomarkers and cognition. Additionally, mediation analysis was conducted through 10,000 bootstrapped iterations to explore potential links between carotid plaque, AD pathology, and cognition. Results: We found that carotid plaque exhibited significant correlations with A beta(42) (beta = -1.173, p = 0.022), A beta(42)/A beta(40) (beta = -0.092, p < 0.001), P-tau/A beta(42) (beta = 0.110, p = 0.045), and T-tau/A beta(42) (beta = 0.451, p = 0.010). A significant correlation between carotid plaque and cognition decline was also found in men (beta = -0.129, p = 0.021), and mediation analyses revealed that the effect of carotid plaque on cognitive function could be mediated by A beta(42)/A beta(40) (proportion of mediation = 55.8%), P-tau/A beta(42) (proportion of mediation = 51.6%, p = 0.015) and T-tau/A beta(42) (proportion of mediation = 43.8%, p = 0.015) mediated. Conclusions: This study demonstrated the link between carotid plaque and CSF AD biomarkers in cognitively intact adults, and the important role that AD pathology may play in the correlation between carotid plaque and cognitive changes.