Association of herpes zoster with dementia: A systematic review and meta-analysis with GRADE assessment

Background Herpes zoster (HZ) is the reactivation of varicella zoster virus predominantly affecting individuals aged over 50 years. Dementia is a prevalent age-related condition. The association between HZ and dementia was under dispute. Objectives The objective of this study was to evaluate the evidence on the association of HZ with dementia. Methods We conducted a systematic review and meta-analysis to evaluate the risk of dementia in individuals with a history of HZ compared to those without such a history. We searched PubMed, Embase, Medline, and Cochrane Library for studies published up to February 24, 2024. The risk of bias of studies was examined by the Newcastle–Ottawa Scale. A random effects model meta-analysis was performed to calculate the pooled hazard ratio (HR) and odds ratio (OR) with 95% confidence interval (CI). Subgroup analyses on Alzheimer’s disease (AD), vascular dementia (VD), and cranial nerve involvement of HZ were executed. We used the GRADE methodology to assess the certainty of evidence. Results We included seven cohorts and two case–control studies involving 3,550,251 subjects. The risk of bias of included studies was generally low. The meta-analysis found no association of HZ with dementia (pooled HR 1.00, 95% CI 0.94–1.07 for cohort studies; pooled OR 1.05, 95% CI 0.84–1.30 for case-control studies), with the certainty of evidence being very low. Subgroup analyses for AD, VD, and cranial never HZ also revealed no significant differences (pooled HR being 0.99, 95% CI 0.89–1.09; 1.04, 95% CI 0.85–1.27; and 1.36, 95% CI 0.76–2.43, respectively). Conclusion The current evidence does not support an association of HZ with dementia.