Association between varicella-zoster virus and Alzheimer's disease: A systematic review and meta-analysis of comprehensive evidence from infection, treatment to prevention

BackgroundThe association between varicella-zoster virus (VZV) infection and Alzheimer's disease (AD) risk has shown inconsistent results. Given difficulties in early diagnosis and limited therapeutic options for AD, identifying modifiable risk factors is significant for prevention.ObjectiveTo systematically evaluate the impact of VZV infection on AD risk and explore protective effects of antiviral treatment and vaccination.MethodsWe searched PubMed and Web of Science databases up to April 2025. The Newcastle-Ottawa Scale assessed study quality. Random-effects models were used for meta-analysis using risk ratios (RR) as the primary effect measure, with sensitivity and subgroup analyses conducted.ResultsTwenty-one studies were included. Meta-analysis showed: (1) herpes zoster patients had significantly higher AD risk (RR = 1.12, 95% CI: 1.01-1.24, p = 0.04); (2) patients receiving antiviral treatment had lower AD risk (RR = 0.55, 95% CI: 0.37-0.82, p = 0.003); (3) vaccinated individuals had lower AD risk (RR = 0.72, 95% CI: 0.68-0.78, p < 0.0001). The strongest association occurred in the >70 years age group, demonstrating age as an important effect modifier.ConclusionsThis meta-analysis provides systematic evidence supporting that VZV infection increases AD risk while confirming protective effects of antiviral treatment and vaccination. These findings support including herpes zoster vaccination in preventive healthcare for elderly populations.