Herpes simplex virus infection and the risk of dementia: a systematic review and meta-analysis

Aim: The authors aimed to perform a meta-analysis to evaluate the association between herpes simplex virus (HSV) infection and the risk of developing dementia.Methods: The authors searched the following databases: PubMed, Scopus, Cochrane Library, and Web of Science. The authors included any randomized control trials and controlled observational studies that investigated the prevalence of dementia in HSV-infected patients and HSV-free control group. Also, if the studies measured the levels of HSV antibodies and incidence of these antibodies in patients with dementia compared with a healthy control group.Results: After a comprehensive literature search, 19 studies were included in the meta-analysis with 342 535 patients included in the analysis. The pooled analysis showed a statistically significant association between Alzheimer's disease (AD), mild cognitive impairment (MCI), and increased levels of IgG titer group [mean difference (MD) = 0.99, 95% confidence interval (CI) = 0.36-1.63, P-value = 0.002], (MD = 0.80, 95% CI = 0.26-1.35, P-value = 0.004), respectively. Additionally, the generic inverse variance showed a statistically significant association between the HSV group and increased incidence of dementia compared with the no HSV control group [risk ratio (RR) = 2.23, 95% CI = 1.18-2.29, P-value <0.00001]. Moreover, this analysis showed no statistically significant difference between the AD group and the control group in anti-HSV IgM titer n (%) outcome (RR = 1.35, 95% CI = 0.91-2.01, P-value = 0.14), respectively.Conclusion: This study revealed that AD and MCI patients have increased levels of IgG antibodies titer against HSV infection. The study showed a significant association between HSV infection and increased incidence of dementia. Thus, regular follow-up of HSV patients' IgG titer levels could be useful in the prevention of dementia in these patients.