Bonus!

A bonus from the shingles vaccine: Dementia protection?

The study shows a sharp change when the vaccine was introduced in Wales.

John Timmer – Apr 3, 2025 2:39 PM | 131

Credit: Cavan Images

A study released on Wednesday finds that a live-virus vaccine that limits shingles symptoms was associated with a drop in the risk for dementia when it was introduced. The work took advantage of the fact that the National Health Service Wales made the vaccine available with a very specific age limit, essentially creating two populations, vaccinated and unvaccinated, separated by a single date. And these populations showed a sharp divide in how often they were diagnosed with dementia, despite having little in the way of other differences in health issues or treatments.

What a day

This study didn't come out of nowhere. There have been a number of hints recently that members of the herpesvirus family that can infect nerve cells are associated with dementia. That group includes Varicella zoster, the virus that causes both chicken pox and—potentially many years after— shingles, an extremely painful rash. And over the past couple of years, observational studies have suggested that the vaccine against shingles may have a protective effect.

But it's extremely difficult to do a clinical trial given that the onset of dementia may happen decades after most people first receive the shingles vaccine. That's why the use of NHS Wales data was critical. When the first attenuated virus vaccine for shingles became available, it was offered to a subset of the Welsh population. Those who were born on or after September 2, 1933, were eligible to receive the vaccine. Anyone older than that was permanently ineligible.

(The UK NHS considers things like the cost/benefit of treatments, and likely took into account the potential impact of the side effects on the elderly in making this decision.)

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This created what's termed a natural experiment, in that the populations born a few weeks on either side of this data should be roughly equivalent in terms of health risks and cumulative exposure. The only real difference is whether or not they were likely to get the vaccine. And health records indicated that only 0.01 percent of those in the ineligible group did, while nearly half of those eligible received it.

So residents of Wales born on either side of the dividing date were matched according to their use of preventative health services, past diagnoses, and educational level. The incidence of dementia was then compared between people on either side of September 2, 1933. As a first step, the researchers confirmed that the vaccine was effective at reducing the incidence of shingles, with numbers similar to those in the vaccine's clinical trials.

Overall, being eligible for the vaccine was associated with a 1.3 percent reduction in the absolute risk of a dementia diagnosis. That translates to an 8.5 percent reduction of relative risk; when scaled to account for the fact that fewer than half of those eligible received the vaccine, that works out to be a 20 percent reduction in relative risk, which is pretty substantial.

To make sure that it was real, the researchers repeated the analysis using a difference-in-difference approach and came up with roughly the same numbers. That also eliminates the possibility that people who came in for health care (for shingles or some other condition) were more likely to incidentally receive a dementia diagnosis. They also compared the before-and-after populations in terms of a collection of common health outcomes and found that none of those showed any change in the two populations. And nothing else related to NHS policy was changed based on the September 2 date.

Separately, in a draft manuscript the researchers posted on the Med arXiv, the researchers find a similar effect when using UK HNS data to search for a protective effect of the shingles vaccines when it comes to deaths diagnosed to result from dementia. So by all indications, the effect was real.

What’s going on?

The researchers suggest three potential explanations. One of them is the obvious: Suppressing the reactivation of the varicella zoster virus reduces dementia onset. But it's also possible that the effect is indirect—that dementia is associated with immune activity, and the vaccine alters that in some way. Finally, there's the possibility that being treated for shingles could promote the onset of dementia or increase the frequency of diagnoses.

The last question was fairly easy to answer. The researchers note yet again that other chronic diagnoses show a change at around the critical date. And they also adjusted their analysis to control for the frequency of medical care. The subgroup that interacted with the NHS most often showed roughly the same protection by the vaccine as the group as a whole did. Finally, the researchers note that shingles diagnosis and treatment didn't increase the probability of dementia diagnoses.

In contrast, there is some evidence that the effect is related to the activation of the virus. People who experienced multiple shingles events were more likely to receive a dementia diagnosis. And people who received an antiviral treatment in response to shingles had a reduced incidence of dementia.

But there were also differences that suggest the immune response in general may be involved. Those who are prone to autoimmune or allergic responses (which are more common in women) showed a greater protection from the vaccine, as did women. These effects aren't large, but they may provide a hint that there's something more than a specific response to one virus.

Following up on these results, however, will be complicated. While most people associate the onset of dementia in the elderly with Alzheimer's, there are a number of distinct dementia diagnoses, often with risk factors and underlying biology that only partly overlap. In many cases, there's no easy way to distinguish between some of them. So there's the chance that these results represent an even stronger effect that's specific to a subset of the known dementias.

But at least from a medical perspective, it doesn't really matter. The vaccine is highly effective at preventing severe cases of shingles, and it seems to significantly reduce the frequency of dementia. There is even less reason to avoid getting it.

Nature, 2025. DOI: 10.1038/s41586-025-08800-x (About DOIs).

John Timmer Senior Science Editor

John is Ars Technica's science editor. He has a Bachelor of Arts in Biochemistry from Columbia University, and a Ph.D. in Molecular and Cell Biology from the University of California, Berkeley. When physically separated from his keyboard, he tends to seek out a bicycle, or a scenic location for communing with his hiking boots.

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