Carotid atherosclerosis associated with tau pathology and cognitive function in cognitively intact adults: the CABLE study

Abstract Background Carotid atherosclerosis has been implicated in cognitive decline, but the evidence from current studies is insufficient and the detailed mechanism remains unclear. Objective This study aimed to explore the association of carotid atherosclerosis with cognitive function and cerebrospinal fluid (CSF) Alzheimer's disease (AD) biomarkers, as well as attempted to investigate the underlying mechanisms. Methods This study included 365 participants with objective normal cognition from the Chinese Alzheimer’s Biomarker and LifestylE (CABLE) database. Multiple linear regression models were utilized to assess the associations of carotid atherosclerosis (carotid intima-media roughness [CIMR], carotid intima-media thickness [CIMT], carotid plaque, and CIMT level) with CSF AD biomarkers and cognitive function. The mediation analyses were used to explore whether CSF AD biomarkers mediated the carotid atherosclerosis and cognitive function. Result We found that CIMR, carotid plaque, and CIMT level were significantly associated with tau pathology (T-tau and P-tau, P < 0.05); All markers of carotid atherosclerosis were associated with cognitive function (CM-MMSE and MoCA, P < 0.05). Furthermore, mediation analyses revealed that the effect of carotid plaque on cognitive decline was partially mediated by tau pathology (proportion of mediation = 19.7%, P = 0.012). Conclusion This study indicated that carotid atherosclerosis was associated with tau pathology and cognitive function, and tau pathology partially mediated the association between carotid atherosclerosis and cognitive function.