AbstractBackgroundThere is growing recognition that infectious agents, particularly herpesviruses, could play a role in the development of some types of dementia.MethodIn Wales, eligibility for the herpes zoster vaccine (Zostavax) for shingles prevention was determined based on an individual’s exact date of birth. Those born before September‐2‐1933 were ineligible (and remained ineligible for life), while those born on or after September‐2‐1933 were eligible. This natural experiment provides causal, as opposed to correlational, evidence because there is no plausible reason why adults born just one week apart should differ systematically from each other. We used a regression discontinuity design in Welsh country‐wide data on primary and secondary care encounters, and death certificates. The outcome was a new dementia diagnosis as recorded in any of these data sources.ResultWe included 282,541 individuals born between September‐1‐1925 and August‐31‐1941. The percentage who received the zoster vaccine increased from 0.01% among those one week too old to be eligible, to 47.2% among those one week younger. Receiving the vaccine reduced the probability of a new dementia diagnosis over a follow‐up period of seven years by 3.5 percentage points (95% CI: 0.6‐7.1, p = 0.019), corresponding to a 22.4% relative decrease. There were significant protective effects from the vaccine for Alzheimer’s disease but not vascular dementia. Effects were far stronger among women than men. To demonstrate that our approach is causal, we show that i) there were no differences in pre‐existing conditions or uptake of other preventive interventions across the date‐of‐birth eligibility cutoff; ii) the zoster vaccine had no effects on any other common causes of morbidity and mortality; and iii) no other interventions used the same date‐of‐birth eligibility cutoff.ConclusionIn addition to identifying a readily available preventive intervention for dementia, our findings strongly suggest an important role of the varicella zoster virus in the etiology of dementia, particularly among women. Unlike existing studies in this field, this analysis provides causal evidence because individuals who differ in age by just one week are exchangeable with each other on both observed and unobserved characteristics, except for a large difference in the probability of receiving the zoster vaccine.