Background

Human herpesvirus (HHV) infections, particularly for herpes simplex virus (HSV) and varicella-zoster virus (VZV), may increase dementia risk, yet the protective effects of anti-herpetic medications remained unclear.

Objective

This systematic review and meta-analysis of observational studies aimed to examine the association between anti-herpetic medications and dementia, focusing on HSV or VZV-related infections.

Methods

This study followed PRISMA guidelines (CRD42022368318). Cohort or nested case-control studies published from databases’ inception to December 2024 were systematically searched in PubMed, MEDLINE, Embase, Cochrane Library, PsycINFO, and Web of Science. Eligible studies evaluated anti-herpetic medications (e.g., acyclovir, famciclovir, ganciclovir, valacyclovir, valganciclovir) and dementia risk in non-demented adults aged ≥50. Pooled adjusted hazard ratios (aHR) and 95% confidence intervals (CIs) were analyzed using random-effects models. Subgroup and meta-regression analyses were performed to explore potential sources of heterogeneity and effect modifiers.

Results

Fourteen cohort studies involving more than 10 million older adults were included. To demonstrate the effects of anti-herpetic medications in various clinical scenarios, the meta-analysis compared: diagnosed and treated versus diagnosed but untreated (aHR=0.77, 95% CI: 0.67–0.89); treated versus untreated regardless of diagnosis (aHR=0.90, 95% CI: 0.87–0.94); and diagnosed and treated versus neither diagnosed nor treated (aHR=0.87, 95% CI: 0.78–0.97). Subgroup analysis and meta-regression identified infection severity as a significant modifier (p < 0.0001), explaining 89.01% of heterogeneity.

Conclusions

This systematic review and meta-analysis reveals notable protective effect of anti-herpetic medication usage on dementia, and the effect is especially pronounced in patients with severe alpha herpesvirus infections.

Search results

Anti-herpetic treatment reduces dementia risk: A systematic review and meta-analysis

Acupuncture in the Management of Herpes Zoster