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Carotid Atherosclerosis Associated with Tau Pathology and Cognitive Function in Cognitively Intact Adults: The Chinese Alzheimer's Biomarker and Lifestyle (CABLE) Study

Ming-Zhan Zhang1, Cheng-Kun Sun2, Yan-Ming Chen3, Quan Hao3, Zi-Qi Zhang1, Fan Guo3, Lan Tan1,2,3,4, Meng-Shan Tan1,2,3,4*

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 (Total Tau) and P-tau (Phosphorylated Tau), p<0.05); all markers of carotid atherosclerosis were associated with cognitive function (CM-MMSE (China-Modied Mini-Mental State Examination) and MoCA (Montreal Cognitive Assessment), 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.

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