Circulating Amyloid-β and Methionine-Related Metabolites to Predict the Risk of Mild Cognitive Impairment: A Nested Case-Control Study

Article type: Research Article

Authors: Fu, Jingzhu^{a; f; 1} | Zhu, Yun^{b; f; 1} | Sun, Yue^{a; f} | Liu, Qian^{a; f} | Duan, Huilian^{a; f} | Huang, Ling^{a; f} | Zhou, Dezheng^{a; f} | Wang, Zehao^{a; f} | Zhao, Jing^{a; f} | Li, Zhenshu^{a; f} | Du, Yue^{c; f} | Liu, Huan^{a; f} | Ma, Fei^{b; f} | Chen, Yongjie^{b; f} | Sun, Changqing^d | Wang, Guangshun^e | Li, Wen^{a; f; *} | Huang, Guowei^{a; f; *}

Affiliations: [a] Department of Nutrition & Food Science, School of Public Health, Tianjin Medical University, Tianjin, China | [b] Department of Epidemiology & Biostatistics, School of Public Health, Tianjin Medical University, Tianjin, China | [c] Department of Social Medicine and Health Management, School of Public Health, Tianjin Medical University, Tianjin, China | [d] Neurosurgical Department of Baodi Clinical College of Tianjin Medical University, Tianjin, China | [e] Department of Tumor, Baodi Clinical College of Tianjin Medical University, Tianjin, China | [f] Tianjin Key Laboratory of Environment, Nutrition and Public Health, Tianjin, China

Correspondence: [*] Correspondence to: Guowei Huang, Professor, PhD, Department of Nutrition and Food Science, School of Public Health, Tianjin Medical University, No 22 Qixiangtai Road, Heping District, Tianjin 300070, China. Tel./Fax: +86 22 83336603; E-mail: huangguowei@tmu.edu.cn. and Wen Li, Associate Professor, PhD, Department of Nutrition and Food Science, School of Public Health, Tianjin Medical University, No 22 Qixiangtai Road, Heping District, Tianjin 300070, China. E-mail: liwen828@tmu.edu.cn.

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

Abstract: Background:The high cost, limited availability, and perceived invasiveness of amyloid PET and cerebrospinal fluid biomarkers limit their use for the diagnosis of Alzheimer’s disease. Objective:The present study aimed to assess the associations of mild cognitive impairment (MCI) with circulating amyloid-β (Aβ), methionine circulating metabolites (MCMs), and their downstream products, and to develop a nomogram based on these easily accessible blood indexes for the individualized prediction of MCI risk in older adults. Methods:In this nested case-control study, we recruited 74 MCI patients and, for each, 3 matched controls (n = 222) within the context of the Tianjin Elderly Nutrition and Cognition (TENC) cohort, a population-based prospective study in China. Concentrations of Aβ, MCMs, and their circulating downstream factors (i.e., leukocyte telomere length and inflammatory cytokines) were evaluated in fasting blood sample using standard procedures. We constructed a nomogram for MCI harnessed multivariable logistic models incorporating variables selected in the Lasso regression. Results:Among the many biomarkers examined, the final prediction nomogram retained only 3 factors: Aβ42/Aβ40 ratio, Hcy, and SAM/SAH ratio. The model achieved favorable discrimination, with a C-statistic of 0.75 (95% confidence interval 0.69–0.81) in internal validation after adjustment of optimism. The calibration accuracy was satisfactory; the Brier score of the model was 0.161 in internal validation after adjustment of optimism. Conclusion:his study presents an individualized prediction nomogram incorporating only three blood biomarkers (i.e., Aβ42/Aβ40 ratio, Hcy, and SAM/SAH ratio), which can be conveniently utilized to facilitate early identification and the development of high-risk prevention strategies for MCI in older adults.

Keywords: Inflammatory factor, leukocyte telomere length, methionine circulating metabolites, mild cognitive impairment, nested case-control study, older adult, plasma amyloid-β, predictive model

DOI: 10.3233/JAD-220373

Journal: Journal of Alzheimer's Disease, vol. 90, no. 1, pp. 389-404, 2022