Associations of Infectious Agents with Alzheimer’s Disease: A Systematic Review and Meta-Analysis

Article type: Research Article

Authors: Ou, Ya-Nan^{a; 1} | Zhu, Jun-Xia^{b; 1} | Hou, Xiao-He^a | Shen, Xue-Ning^a | Xu, Wei^a | Dong, Qiang^b | Tan, Lan^{a; *} | Yu, Jin-Tai^{c; *}

Affiliations: [a] Department of Neurology, Qingdao Municipal Hospital, Qingdao University, Qingdao, China | [b] Department of Prevention and Health Protection, Huashan Hospital, Shanghai Medical College, Fudan University, Shanghai, China | [c] Department of Neurology and Institute of Neurology, Huashan Hospital, Shanghai Medical College, Fudan University, Shanghai, China

Correspondence: [*] Correspondence to: Dr. Jin-Tai Yu, Department of Neurology, Huashan Hospital, Fudan University, No. 12 Wulumuqi Road, Shanghai, China. Tel.: +86 532 8890 5659; Fax: +86 532 8890 5659; E-mail: [email protected] and Dr. Lan Tan, Department of Neurology, Qingdao Municipal Hospital, Qingdao University, No.5 Donghai Middle Road, Qingdao, China. E-mail: [email protected].

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

Abstract: Background:The role of infectious agents in the development of Alzheimer’s disease (AD) has long been debated, however, uncertainties still persist. Objective:We aimed to illuminate the associations between infectious agents and risk of AD comprehensively. Methods:Studies examining the associations between AD and infectious agents were identified through a systematic search of PubMed, Embase, and Cochrane library. A random-effects meta-analysis was conducted. Publication bias was explored using funnel plot. Results:Fifty-one studies were included in the systematic review, of which forty-seven studies with 108,723 participants and 4,039 AD cases were eligible for meta-analysis. Evidence based on case control studies demonstrated that Chlamydia pneumoniae [odds ratio (OR): 4.39, 95% CI = 1.81–10.67; I2 = 68%)], Human herpes virus-6 (OR: 3.97, 95% CI = 2.04–7.75; I2 = 0%, Epstein-Barr virus (OR:1.45, 95% CI = 1.00–2.08; I2 = 0%), Herpes simplex virus-1 (OR:1.34, 95% CI = 1.02–1.75; I2 = 0%), and the Herpesviridae family (OR:1.41, 95% CI = 1.15–1.74; I2 = 12%) infection were associated with a higher risk of AD. No significant evidence of publication bias was found. Conclusion:These findings strengthened the evidence that infection may play an important role in AD. Additional research is required to determine whether treatment strategies targeting infectious diseases to prevent AD are viable in the future.

Keywords: Alzheimer’s disease, Chlamydia pneumoniae, Herpesviridae, infectious, meta-analysis

DOI: 10.3233/JAD-191337

Journal: Journal of Alzheimer's Disease, vol. 75, no. 1, pp. 299-309, 2020