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

Article type: Research Article

Authors: Sun, Cheng-Kun^{a; 1} | Guo, Fan^{b; 1} | Ou, Ya-Nan^b | Zhang, Ming-Zhan^c | Tan, Lan^{a; b; c; d; *} | Tan, Meng-Shan^{a; b; c; d; *}

Affiliations: [a] Department of Neurology, Qingdao Municipal Hospital, Dalian Medical University, Qingdao, China | [b] Department of Neurology, Qingdao Municipal Hospital, Qingdao University, Qingdao, China | [c] School of Clinical Medicine, Shandong Second Medical University, Weifang, Shandong, China | [d] Department of Neurology, Qingdao Municipal Hospital, University of Health and Rehabilitation Science, Qingdao, China

Correspondence: [*] Correspondence to: Meng-Shan Tan, MD, PhD, and Lan Tan, MD, PhD, Department of Neurology, Qingdao Municipal Hospital, University of Health and Rehabilitation Science, Qingdao, China. E-mail: [email protected]; [email protected].

Note: [1] These authors contributed equally to this work.

Abstract: 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 Aβ42 (β = –1.173, p = 0.022), Aβ42/Aβ40 (β = –0.092, p < 0.001), P-tau/Aβ42 (β = 0.110, p = 0.045), and T-tau/Aβ42 (β = 0.451, p = 0.010). A significant correlation between carotid plaque and cognition decline was also found in men (β = –0.129, p = 0.021), and mediation analyses revealed that the effect of carotid plaque on cognitive function could be mediated by Aβ42/Aβ40 (proportion of mediation = 55.8%), P-tau/Aβ42 (proportion of mediation = 51.6%, p = 0.015) and T-tau/Aβ42 (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.

Keywords: Alzheimer’s disease, biomarkers, carotid plaque, cognitive function, pathogenesis

DOI: 10.3233/JAD-240131

Journal: Journal of Alzheimer's Disease, vol. 100, no. 1, pp. 207-217, 2024