Herpes zoster as risk factor for dementia: a matched cohort study over 20 years in a 10-million population in Italy

Background: Herpes Zoster is caused by the reactivation of the Varicella-Zoster Virus. Zoster may influence the occurrence of dementia, but contradictory results about this association emerged from recent studies. These findings did not consider the severity of Zoster and observed individuals for limited follow-up time. Our study used a region-wide Italian registry to investigate the association between severe Zoster infection and dementia occurrence over a 23-year period. Methods: We included people aged ≥ 50 and hospitalised with Zoster, and two comparison cohorts from both the general population and the hospitalised population without Zoster. By random sampling, the matching 1:5 was based on sex, birth year, and entry date in the cohort. Dementia and Zoster were identified through validated algorithms. A Fine-Gray sub-distribution hazard model was used, accounting for competing risk of death. Results: We identified 132,968 individuals, of whom 12,088 with severe Zoster, 60,440 matched controls among the general population, and 60,440 matched controls among the hospitalised population. In severe cases of Herpes Zoster, the overall adjusted sub-distributed hazard ratio of dementia was 1.13 (95 % CI 1.07-1.19) compared to the general population, and 1.08 (95 % CI 1.03-1.14) compared to hospitalised population. Hazard ratios were still significant in different strata group, including by sex, age group (including in 50-65 younger adults) and at different follow-up period. Conclusions: Our population-based study found an increased risk of developing dementia among severe Zoster cases. Those results support the importance of improving Zoster prevention and extending the vaccination recommendations to younger age groups.