Study strengthens link between shingles vaccine and lower dementia risk

“It was a really striking finding,” Geldsetzer said. “This huge protective signal was there, any which way you looked at the data.”

The scientists searched high and low for other variables that might have influenced dementia risk but found the two groups to be indistinguishable in all characteristics. There was no difference in the level of education between the people who were eligible and ineligible, for example. Those who were eligible were not more likely to get other vaccinations or preventive treatments, nor were they less likely to be diagnosed with other common health conditions, such as diabetes, heart disease and cancer.

The only difference was the drop in dementia diagnoses.

“Because of the unique way in which the vaccine was rolled out, bias in the analysis is much less likely than would usually be the case,” Geldsetzer said.

Nevertheless, his team analyzed the data in alternate ways — using different age ranges or looking only at deaths attributed to dementia, for example — but the link between vaccination and lower dementia rates remained.

“The signal in our data was so strong, so clear and so persistent,” he said.

Stronger response in women

In a further finding, the study showed that protection against dementia was much more pronounced in women than in men. This could be due to sex differences in immune response or in the way dementia develops, Geldsetzer said. Women on average have higher antibody responses to vaccination, for example, and shingles is more common in women than in men.

Whether the vaccine protects against dementia by revving up the immune system overall, by specifically reducing reactivations of the virus or by some other mechanism is still unknown.

Also unknown is whether a newer version of the vaccine, which contains only certain proteins from the virus and is more effective at preventing shingles, may have a similar or even greater impact on dementia.

Geldsetzer hopes the new findings will inspire more funding for this line of research.

“At least investing a subset of our resources into investigating these pathways could lead to breakthroughs in terms of treatment and prevention,” he said.

In the past two years, his team has replicated the Wales findings in health records from other countries, including England, Australia, New Zealand and Canada, that had similar rollouts of the vaccine. “We just keep seeing this strong protective signal for dementia in dataset after dataset,” he said.

But Geldsetzer has set his sights on a large, randomized controlled trial, which would provide the strongest proof of cause and effect. Participants would be randomly assigned to receive the live-attenuated vaccine or a placebo shot.

“It would be a very simple, pragmatic trial because we have a one-off intervention that we know is safe,” he said.

Geldsetzer is seeking philanthropic funding for the trial as the live-attenuated vaccine is no longer manufactured by pharmaceutical companies.  

And such a trial might not take long to see results. He pointed to a graph of the Wales data tracking the dementia rates of those who were eligible and ineligible for the vaccine. The two curves began to separate in about a year and a half.

A researcher from the Vienna University of Economics and Business also contributed to the work.

The study received funding from The Phil & Penny Knight Initiative for Brain Resilience, the National Institute on Aging (grant R01AG084535), the National Institute of Allergy and Infectious Diseases (grant DP2AI171011), and Chan Zuckerberg Biohub.