A Natural Experiment on the Effect of Herpes Zoster Vaccination on Dementia

A Natural Experiment on the Effect of Herpes Zoster Vaccination on Dementia

Dementia

Markus Eyting, Min Xie, Felix Michalik, Simon Heß, Seunghun Chung, Pascal Geldsetzer

Nature

Vol. 641

2025

Springer Nature

Journal article

English

14764687

Open Access

Neurotropic herpesviruses may be implicated in the development of dementia. Moreover, vaccines may have important off-target immunological effects. Here we aim to determine the effect of live-attenuated herpes zoster vaccination on the occurrence of dementia diagnoses. To provide causal as opposed to correlational evidence, we take advantage of the fact that, in Wales, eligibility for the zoster vaccine was determined on the basis of an individual’s exact date of birth. Those born before 2 September 1933 were ineligible and remained ineligible for life, whereas those born on or after 2 September 1933 were eligible for at least 1 year to receive the vaccine. Using large-scale electronic health record data, we first show that the percentage of adults who received the vaccine increased from 0.01% among patients who were merely 1 week too old to be eligible, to 47.2% among those who were just 1 week younger. Apart from this large difference in the probability of ever receiving the zoster vaccine, individuals born just 1 week before 2 September 1933 are unlikely to differ systematically from those born 1 week later. Using these comparison groups in a regression discontinuity design, we show that receiving the zoster vaccine reduced
the probability of a new dementia diagnosis over a follow-up period of 7 years by 3.5 percentage points (95% confidence interval (CI) = 0.6–7.1, P = 0.019), corresponding to a 20.0% (95% CI = 6.5–33.4) relative reduction.

Jessica Alston