Effects of herpes zoster infection, antivirals and vaccination on risk of developing dementia: A systematic review and meta-analysis.

Herpes zoster (HZ) is a neurotropic virus. We aimed to evaluate the association of HZ infection, protective effects of antiviral treatment or vaccination on dementia. A systematic search of PubMed, MEDLINE, EMBASE, Scopus, Web of Science, CINAHL, and Cochrane CENTRAL was performed from January 1, 1996, to October 31, 2024. Observational studies evaluating HZ infection, antivirals, or vaccination and dementia risk were selected. Risk of bias was examined with the Newcastle-Ottawa scale. A random-effects meta-analysis was performed, with the rate ratio (RR) and corresponding 95% confidence intervals (CIs) being pooled for dementia. Presence of heterogeneity was assessed with I2, and differences by study-level characteristics were estimated using subgroup meta-analysis and meta-regression. Eighteen studies (N = 9.4 million) were included. Infection was associated with elevated risk of dementia (RR 1.14; 95% CI: 1.04, 1.25, I2 = 98%); this remained significant in the sensitivity analysis when the two case-control studies were removed (RR 1.17; 95% CI: 1.06, 1.30, I2 = 98%). Subgroup analysis based on sex, age, study population, bias scores, type of dementia or HZO did not show statistically significant differences in risk. Treatment with antivirals showed a small effect (RR 0.84; 95% CI: 0.71, 0.99, I2 = 73%), but prophylaxis with HZ vaccination was associated with a significantly lower risk (RR 0.68; 95% CI: 0.56, 0.83, I2 = 99%). We report a slightly raised dementia risk after HZ infection and reduced risks after antiviral treatment and prevention with vaccination. However, results should be interpreted with caution due to significant heterogeneity in pooled analyses.