Left Ventricular Ejection Fraction and Cerebrospinal Fluid Biomarkers of Alzheimer’s Disease Pathology in Cognitively Normal Older Adults: The CABLE Study

Article type: Research Article

Authors: Zheng, Yi-Ming^{a; 1} | Zhao, Yang-Yang^{b; 1} | Zhang, Ting^{c; 1} | Hou, Xiao-He^{d; 1} | Bi, Yan-Lin^{e; 1} | Ma, Ya-Hui^d | Xu, Wei^d | Shen, Xue-Ning^c | Dong, Qiang^c | Tan, Lan^{a; d; *} | Yu, Jin-Tai^{a; c; *}

Affiliations: [a] Department of Neurology, Qingdao Municipal Hospital, Shandong First Medical University & Shandong Academy of Medical Sciences, China | [b] Department of Cardiology, Hospital of The People’s Liberation Army Navy, China | [c] Department of Neurology and Institute of Neurology, Huashan Hospital, Shanghai Medical College, Fudan University, China | [d] Department of Neurology, Qingdao Municipal Hospital, Qingdao University, China | [e] Department of Anesthesiology, Qingdao Municipal Hospital, Qingdao University, China

Correspondence: [*] Correspondence to: Jin-Tai Yu, MD, PhD, Department of Neurology, Huashan Hospital, Fudan University, 12th Wulumuqi Zhong Road, Shanghai 200040, China. Tel.: +86 21 52888160; Fax: +86 21 62483421; E-mail: jintai_yu@fudan.edu.cn.; Lan Tan, MD, PhD, Department of Neurology, Qingdao Municipal Hospital, School of Medicine, Qingdao University, No.5 Donghai Middle Road, Qingdao, China. E-mail: dr.tanlan@163.com.

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

Abstract: Background: Heart failure has been considered as a potential modifiable risk factor for cognitive impairment and dementia. Left ventricular ejection fraction (LVEF), an indicator of cardiac dysfunction, has also been associated with cognitive aging. However, the effect of LVEF on Alzheimer’s disease (AD) pathology is still less known. Objective: We aimed to investigate the associations of LVEF with cerebrospinal fluid (CSF) biomarkers for AD in cognitively normal elders. Methods: A total of 423 cognitively normal individuals without heart failure were included from the Chinese Alzheimer’s Biomarker and LifestylE (CABLE) study. Participants were divided into low LVEF group (50%≤LVEF < 60%) and high LVEF group (LVEF≥60%). The associations of LVEF with CSF AD biomarkers including CSF amyloid-β 42 (Aβ42), total-tau (t-tau), and phosphorylated tau (p-tau) were analyzed using multivariate linear regression models. Results: Participants with low LVEF had higher levels of CSF t-tau (β= –0.009, p = 0.006) and t-tau/Aβ42 ratios (β= –0.108, p = 0.026). Subgroup analyses showed that the associations only existed in female and middle-aged groups (< 65 years old). Besides, participants with low LVEF had higher levels of CSF p-tau (β= –0.002, p = 0.043) in middle-aged group. Conclusion: In conclusion, our findings revealed the associations between LVEF and AD pathology, which may provide new insights into AD prevention through maintaining cardiac function.

Keywords: Alzheimer’s disease, biomarker, cerebrospinal fluid, left ventricular ejection fraction

DOI: 10.3233/JAD-201222

Journal: Journal of Alzheimer's Disease, vol. 81, no. 2, pp. 743-750, 2021