Study finds strongest evidence yet that shingles vaccine helps cut dementia risk | A natural experiment on the effect of herpes zoster vaccination on dementia

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https://www.theguardian.com/society/2025/apr/02/study-finds-strongest-evidence-yet-that-shingles-vaccine-helps-cut-dementia-risk

[u/Hrmbee]

From the news report:

Pascal Geldsetzer, at Stanford University, said: “For the first time we are able to say much more confidently that the shingles vaccine causes a reduction in dementia risk. If this truly is a causal effect, we have a finding that’s of tremendous importance.”

The researchers took advantage of a vaccination rollout that took place in Wales more than a decade ago. Public health policy dictated that from 1 September 2013, people born on or after 2 September 1933 became eligible for the Zostavax shot, while those who were older missed out.

The policy created a natural experiment where the older population was sharply divided into two groups depending on their access to the vaccine. This allowed the researchers to compare dementia rates in older people born weeks apart but on either side of the vaccine eligibility divide.

After accounting for the fact that not all those eligible for the vaccine received it, the researchers found vaccination led to a 20% reduction in dementia risk, with the strongest effect in women. Anupam Jena, a professor of healthcare policy at Harvard Medical School, said the implications were profound.

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It is unclear how shingles vaccines might protect against dementia, but one theory is that they reduce inflammation in the nervous system by preventing reactivation of the virus. Another theory is that the vaccines induce broader changes in the immune system that are protective. These wider effects are seen more often in women, potentially explaining the sex differences in the study.

In an accompanying article, Jena wrote: “Although it is still unclear precisely how herpes zoster vaccination lowers the risk of dementia, the implications of the study are profound. The vaccine could represent a cost-effective intervention that has public-health benefits strongly exceeding its intended purpose.”

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Link to the research: A natural experiment on the effect of herpes zoster vaccination on dementia

Abstract:

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. This protective effect was stronger among women than men. We successfully confirm our findings in a different population (England and Wales’s combined population), with a different type of data (death certificates) and using an outcome (deaths with dementia as primary cause) that is closely related to dementia, but less reliant on a timely diagnosis of dementia by the healthcare system. Through the use of a unique natural experiment, this study provides evidence of a dementia-preventing or dementia-delaying effect from zoster vaccination that is less vulnerable to confounding and bias than the existing associational evidence.