Does shingles vaccination reduce the risk of dementia? Large study hints at link

Vaccination against shingles could also prevent dementia, such as that caused by Alzheimer’s disease, according to a study of the health records of around 300,000 people in Wales. The analysis found that getting vaccinated reduces the risk of dementia by 20%. But some puzzling aspects of the analysis have sparked debate about the robustness of the work.

The study was posted on the medRxiv preprint server on May 25 and has not yet been peer-reviewed.

“If that’s true, that’s huge,” says Alberto Ascherio, an epidemiologist at Harvard University in Cambridge, Massachusetts, who was not involved in the study. “Even a modest reduction in risk has a huge impact.”

Link between dementia and infection

The idea that viral infection may play a role in at least some cases of dementia dates back to the 1990s, when biophysicist Ruth Itzhaki from the University of Manchester, UK, and her colleagues discovered herpes viruses in the brains of deceased people with dementia². The theory has been controversial among Alzheimer’s researchers. But recent work has suggested that people infected with viruses that affect the brain have higher rates of neurodegenerative diseases.³. Research has also suggested that people vaccinated against certain viral diseases are less likely to develop dementia.⁴.

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But all of these epidemiological studies have one key problem in common: People who receive any type of vaccination tend to have healthier lifestyles than those who don’t.⁵which means that other factors could explain their reduced risk of diseases such as Alzheimer’s disease.

With that in mind, epidemiologist Pascal Geldsetzer of Stanford University in California and his colleagues turned to a natural experiment: a shingles vaccination program in Wales, which began September 1, 2013. Shingles is caused by the awakening of the inactive varicella zoster virus (VZV). , THE herpes virus which causes chickenpox and is present in most people. Shingles is more common in older people and can cause severe pain and rashes.

natural experience

Data suggests vaccine is most effective in people under 80. As a result, only people under the age of 80 at the start of the scheme – those born on or after September 2, 1933 – were eligible to receive the jab in Wales. People born before September 2, 1933 were not eligible for life.

Researchers examined the electronic health records of 296,603 people born between 1925 and 1942 and found that about half of those who were eligible were vaccinated within seven years of the vaccine, known as the vaccine, becoming available. by Zostavax. The team also found that people in the eligible group were 8.5% less likely to develop dementia than those who were not eligible. Considering that only about half of eligible people were vaccinated, the researchers calculated that the vaccine reduced the risk of dementia by 19.9% ​​overall.

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The birthday cutoff allowed comparison of people born within weeks of each other. Geldsetzer says there is no plausible reason why people who turned 80 in August would be more prone to dementia than those who had a birthday in September: the only difference is that people whose birthdays are later could get vaccinated against shingles. Any other factor that might affect the incidence of dementia, such as public screening campaigns, would have affected both groups equally.

“I think it’s a very strong paper,” says Ascherio. While it’s possible the different rates of dementia could have occurred by chance, he says the authors performed appropriate tests to rule out any other explanation.

Itzhaki is delighted that this study, among others, supports the theory that viruses are a trigger for Alzheimer’s disease. “It’s totally consistent with what we’ve been saying since 1991 and very gratifying,” she says, adding that the new study is unique in that it rules out other factors that might explain the lower risk of dementia in the vaccinated group.

Confusing find

Others still call for caution. “It’s a well-done study, but it’s by no means conclusive,” says Maria Glymour, an epidemiologist at the University of California, San Francisco who studies Alzheimer’s disease. She points out that most of the differences in dementia rates were recorded in the first four years after vaccination, but Alzheimer’s disease develops over decades. Geldsetzer says it’s possible the vaccine simply delays the onset of dementia, adding that he would like to repeat his analysis in the future, to see if the effect persists beyond seven years.

The authors also found that the effect was predominantly in women: there was no statistically significant difference in dementia rates between eligible and non-eligible men. Geldsetzer isn’t sure why, but notes that women and men seem to have different rates of shingles and dementia.

But critics have seized on this discrepancy to question whether the results prove a causal relationship between the vaccine and dementia. Cornelia van Duijn, an epidemiologist at the University of Oxford, UK, says that while the experiment is “magnificent”, the fact that the men were not affected calls the study into question. “I am not convinced that chance or prejudice are to be excluded,” she says.

Mystery of the mechanism

And it’s unclear why or how the vaccine might prevent dementia, or if a new vaccine called Shingrix, which replaced Zostavax, would have the same effect. Others pointed out that Zostavax was a fairly ineffective vaccine: a clinical trial found it reduced the risk of shingles by around 50%. It’s possible, Geldsetzer says, that the vaccine triggers an immune response that helps reduce the risk of dementia.

Before the results influence policy, adds Glymour, they should be replicated by studying a different group. She and others agree that the best way to confirm the results would be through a clinical trial, rather than a review of health records. Several trials testing new shingles vaccines are underway, and Geldsetzer says it might be possible to study cognitive function in participants.

“It would be good for all of us, because it’s a very important step forward,” says Ascherio. “I hope it’s true.”

Nature recognizes that sex and gender both exist on a spectrum and are not necessarily aligned. The use of the words “women” and “men” here reflects the wording of the study described in the article.