Circulatory Levels of Toxic Metals (Aluminum, Cadmium, Mercury, Lead) in Patients with Alzheimer’s Disease: A Quantitative Meta-Analysis and Systematic Review

Article type: Research Article

Authors: Xu, Lin^a | Zhang, Wenchao^b | Liu, Xianchen^c | Zhang, Cuili^a | Wang, Pin^d | Zhao, Xiulan^{a; *}

Affiliations: [a] Department of Toxicology, School of Public Health, Shandong University, Jinan, China | [b] Department of Epidemiology, School of Public Health, Shandong University, Jinan, China | [c] Department of Clinical Pharmacy, University of Tennessee Health Science Center, Memphis, TN, USA | [d] Department of Neurology, The Second Hospital of Shandong University, Jinan, China

Correspondence: [*] Correspondence to: Xiulan Zhao, Department of Toxicology, School of Public Health, Shandong University, No. 44 Wenhua Xi Road, Jinan, China. Tel.: +86 531 88383132; Fax: +86531 88382129; E-mail: [email protected].

Abstract: Background:Environmental exposure to toxic metals has been postulated to play a role in the pathophysiological processes of Alzheimer’s disease (AD). However, the circulatory levels of toxic metals in AD patients are not consistent in previous studies. Objective:To systematically assess levels of toxic metals (aluminum, mercury, cadmium, lead) in the circulation (blood, serum/plasma) of AD patients and controls. Methods:PubMed, Web of Science, Science Direct, Cochrane Library, and the China National Knowledge Infrastructure (CNKI) were systematically searched to identify studies published up to January 1, 2017. Meta-analyses were performed using random-effects models and the pooled standardized mean difference (SMD) were reported with 95% confidence intervals (CI). Results:We identified 17, 7, 8, and 10 studies for aluminum, mercury, cadmium, and lead, respectively. Meta-analyses showed significantly elevated circulatory levels of aluminum (SMD = 1.08, 95% CI: 0.66, 1.50), mercury (SMD = 0.55, 95% CI, 0.15, 0.95), and cadmium (SMD = 0.62, 95% CI: 0.12, 1.11), whereas lower levels of lead (SMD = –0.23, 95% CI: –0.38, –0.07) in AD patients than in controls. Publication bias was only observed for aluminum studies, but the “trim and fill” analysis showed that the publication bias did not alter the direction of the effect. Sensitivity analyses showed no studies from the pooled analysis changed the results. Conclusion:Compared to controls, circulatory levels of aluminum, mercury, and cadmium are significantly higher but the levels of lead were reduced in AD patients. These findings suggest that elevated aluminum, mercury, and cadmium in the circulation, especially in serum may play a role in the progression of AD.

Keywords: Alzheimer’s disease, circulation, meta-analyses, systematic review, toxic metals

DOI: 10.3233/JAD-170811

Journal: Journal of Alzheimer's Disease, vol. 62, no. 1, pp. 361-372, 2018