In a ‘natural experiment,’ researchers compared dementia diagnoses among people who did or did not receive herpes zoster vaccination.

Several large observational studies have linked herpes zoster (shingles) vaccination to lower risk for developing dementia (for both the original live-attenuated vaccine and the later recombinant vaccine); however, confounding factors might have played heavily in those conclusions. To minimise confounding, an international team took advantage of a natural experiment: when the first shingles vaccine was introduced in Wales on 1 September, 2013, its use was prohibited permanently in people older than 80 years (specifically, people born before 1 September, 1933), because of poor efficacy in older people.

Using a healthcare database that included most Welsh citizens, the researchers were able to identify people who were born just after 1 September, 1933 (and thus eligible for vaccination) and people born just before that date (and thus ineligible). Although these two groups were not generated randomly, they are likely to be very similar. The vaccine-eligible group had an 8.5% relative risk reduction for new diagnoses of dementia during the next seven years (2013 through 2020); recipients of the shingles vaccine (47% of the eligible group) had a 20% reduction in relative risk. Similar results then were noted in a second population from England, in whom death from dementia (rather than newly diagnosed dementia) was assessed as the outcome.

Comment: Plausible mechanisms for why a viral vaccine might lower risk for later dementia include the role of the viruses in contributing to vasculopathy, eliciting neuroinflammation and inducing production of beta amyloid and tau proteins (NEJM JW Gen Med Sep 1 2018 and Neuron 2018; 99: 56-63, 64-82; J Alzheimers Dis 2018; 64: 363-366). If the protective effect of shingles vaccine indeed is causal, it is more efficacious in lowering risk for dementia than any currently available therapy.

Anthony L. Komaroff, MD, Professor of Medicine, Harvard Medical School, Boston, USA.

Eyting M, et al. A natural experiment on the effect of herpes zoster vaccination on dementia. Nature 2025; 641: 438-446.

This summary is taken from the following Journal Watch titles: General Medicine, Ambulatory Medicine, Neurology.