A natural experiment on the effect of herpes zoster vaccination on dementia.
Level 3 - non-randomized controlled study
Quasi-experimental regression discontinuity study (natural experiment cohort).
PubMed 40175543 · doi:10.1038/s41586-025-08800-x
What was done
Researchers evaluated a natural experiment in Wales where live-attenuated herpes zoster vaccine eligibility was determined by a strict date-of-birth cutoff (born on or after 2 September 1933). Using large-scale electronic health records and a regression discontinuity design over a 7-year follow-up, they compared dementia rates between individuals born immediately before and after the threshold. The analysis was also replicated across England and Wales using dementia-related death certificate records.
What was found
Vaccine uptake increased from 0.01% among individuals born 1 week before eligibility to 47.2% among those born 1 week after. Over 7 years, receiving the vaccine reduced the probability of a new dementia diagnosis by 3.5 percentage points (95% CI: 0.6 to 7.1, P = 0.019), reflecting a 20.0% relative reduction (95% CI: 6.5 to 33.4). The protective effect was stronger in women than in men.
Why it matters
By leveraging an exogenous eligibility rule to minimize residual confounding, this study offers robust quasi-experimental evidence that herpes zoster vaccination substantially reduces or delays incident dementia.
Limits
The total sample size is not stated in the abstract. The study evaluated the live-attenuated vaccine rather than newer recombinant formulations, relied on electronic health record diagnoses and death certificates rather than prospective cognitive testing, and cannot distinguish specific neurobiological mechanisms.