Study finds shingles vaccine may lower dementia risk

By Stephen Beech

A vaccine for shingles may lower the risk of dementia, according to new research.

A public health policy in Wales may have produced the strongest evidence yet that a jab can reduce the risk of dementia, say scientists.

Researchers analyzing the health records of older people in Wales discovered that those who received the shingles vaccine were 20% less likely to develop dementia over the next seven years than those who didn't receive the jab.

Scientists say the "remarkable" findings, published in the journal Nature, support an emerging theory that viruses that affect the nervous system can increase the risk of dementia.

If further confirmed, the new findings suggest that a preventive intervention for dementia is already close at hand.

Shingles, a viral infection that produces a painful rash, is caused by the same virus that causes chicken pox, varicella-zoster.

After people contract chicken pox, usually in childhood, the virus remains dormant in the nerve cells for life.

In people who are older or have weakened immune systems, the dormant virus can reactivate and cause shingles.

Years of dementia research has mainly focused on the accumulation of plaques and tangles in the brains of people with Alzheimer’s, the most common form of the debilitating condition.

But with no breakthroughs in prevention or treatment, some researchers are exploring other avenues - including the role of certain viral infections.

Previous studies based on health records have linked the shingles vaccine with lower dementia rates.

But they could not account for a major source of bias: people who are vaccinated also tend to be more health conscious.

Study senior author Dr. Pascal Geldsetzer, of Stanford Medicine in the US, said: “All these associational studies suffer from the basic problem that people who get vaccinated have different health behaviors than those who don’t.

“In general, they’re seen as not being solid enough evidence to make any recommendations on.”

But two years ago, Dr. Geldsetzer recognized a fortuitous “natural experiment” in the rollout of the shingles vaccine in Wales that seemed to sidestep the bias.

The vaccine used at that time contained a live-attenuated, or weakened, form of the virus.

The vaccination program, which began in September 2013, specified that anyone who was 79 was eligible for the vaccine for one year.

The rules, designed to ration the limited supply of the vaccine, also meant that the slight difference in age between 79- and 80-year-olds made all the difference in who had access to the vaccine.

By comparing people who turned 80 just before September 1, 2013, with people who turned 80 just after, the researchers could isolate the effect of being eligible for the vaccine.

Dr. Geldsetzer said the circumstances, well-documented in the country’s health records, were about as close to a randomized controlled trial as possible get without actually conducting one.

The American research team analyzed the health records of more than 280,000 older adults who were 71- to 88-years-old and did not have dementia at the start of the vaccination program.

They focused their analysis on those closest to either side of the eligibility threshold - comparing people who turned 80 in the week before with those who turned 80 in the week after.

Dr. Geldsetzer said: “We know that if you take a thousand people at random born in one week and a thousand people at random born a week later, there shouldn’t be anything different about them on average.

“They are similar to each other apart from this tiny difference in age.

“What makes the study so powerful is that it’s essentially like a randomized trial with a control group - those a little bit too old to be eligible for the vaccine - and an intervention group, those just young enough to be eligible."

Over the next seven years, the research team compared the health of people closest in age who were eligible and ineligible to receive the vaccine.

By factoring in actual vaccination rates, they could derive the effects of receiving the vaccine.

As expected, the vaccine reduced the occurrence over that seven-year period of shingles by about 37% for people who received the vaccine, similar to what had been found in clinical trials of the vaccine.

By 2020, one in eight older adults, who were by then 86 and 87, had been diagnosed with dementia.

But those who received the shingles vaccine were 20% less likely to develop dementia than the unvaccinated.

Dr. Geldsetzer said: “It was a really striking finding.

“This huge protective signal was there, any which way you looked at the data.”

The scientists looked for other variables that might have influenced dementia risk, but the only difference was the drop in dementia diagnoses.

Dr. Geldsetzer said: “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."

He added: “The signal in our data was so strong, so clear and so persistent."

The study also showed that protection against dementia was much more pronounced in women than in men.

Dr Geldsetzer believes that could be because women, on average, have higher antibody responses to vaccination, and shingles is more common in women than in men.

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

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.

Dr. Geldsetzer said: “We just keep seeing this strong protective signal for dementia in dataset after dataset."

He is seeking funding for a larger trial, which would provide the strongest proof of cause and effect, as the live-attenuated vaccine is no longer manufactured by pharmaceutical companies.

Dr. Geldsetzer added: “It would be a very simple, pragmatic trial because we have a one-off intervention that we know is safe."