Journal of Neurovirology · Oct 29, 2026

From latency to neurodegeneration: varicella-zoster virus reactivation and dementia risk, with a focus on herpes zoster ophthalmicus

By Samalia PD, Wang R, Brickell K et al.

Varicella zoster virus (VZV) reactivation has emerged as a potential contributor to dementia through vascular and inflammatory mechanisms, with herpes zoster ophthalmicus (HZO) representing a potentially higher-risk phenotype because of its association with cerebrovascular complications. This narrative review evaluated the epidemiological and mechanistic evidence linking VZV reactivation to cognitive decline. MEDLINE, PubMed, Embase, and the Cochrane Library were searched from inception to March 2026, supplemented by relevant publications identified during revision through October 2026, with emphasis on systematic reviews, large observational studies, quasi-experimental vaccination studies, and mechanistic investigations. Infection-based studies demonstrated heterogeneous findings, with modest associations between herpes zoster and subsequent dementia that frequently attenuated after adjustment for frailty and comorbidity. In contrast, vaccination studies, particularly natural experiments and quasi-experimental analyses, consistently reported lower dementia incidence following zoster immunisation, although causal interpretation and the magnitude of any protective effect remain uncertain. Observational studies suggest that antiviral therapy is associated with fewer short-term cerebrovascular complications, although its relationship with long-term cognitive outcomes remains uncertain. VZV-associated vasculopathy provides the strongest mechanistic rationale for a link with cognitive decline, whereas neuroinflammation, possible blood-brain barrier dysfunction, and interactions with neurodegenerative processes remain proposed pathways. Current evidence suggests that VZV reactivation may accelerate cognitive decline in susceptible individuals, but causality remains unproven. Further prospective studies are needed to clarify the contribution of VZV reactivation and the potential neuroprotective effects of vaccination and antiviral therapy.

doi.org/10.1007/s13365-026-01351-5 PubMed 42955572 Interventions