Tuesday, 1 April 2025

Study strengthens link between shingles vaccine and lower dementia risk

 An unusual public health policy in Wales may have produced the strongest evidence yet that a vaccine can reduce the risk of dementia. In a new study led by Stanford Medicine, researchers analyzing the health records of Welsh older adults discovered that those who received the shingles vaccine were 20% less likely to develop dementia over the next seven years than those who did not receive the vaccine.

The remarkable findings, to be published April 2 in 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.Lifelong infection

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 stays 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.

Dementia affects more than 55 million people worldwide, with an estimated 10 million new cases every year. Decades of dementia research has largely focused on the accumulation of plaques and tangles in the brains of people with Alzheimer's, the most common form of dementia. 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 in myriad, difficult-to-measure ways. Behaviors such as diet and exercise, for instance, are known to influence dementia rates, but are not included in health records.

"All these associational studies suffer from the basic problem that people who get vaccinated have different health behaviors than those who don't," said Pascal Geldsetzer, MD, PhD, assistant professor of medicine and senior author of the new study. "In general, they're seen as not being solid enough evidence to make any recommendations on."

A natural experiment

But two years ago, 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 Sept. 1, 2013, specified that anyone who was 79 on that date was eligible for the vaccine for one year. (People who were 78 would become eligible the next year for one year, and so on.) People who were 80 or older on Sept. 1, 2013, were out of luck -- they would never become eligible for the vaccine.These 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 Sept. 1, 2013, with people who turned 80 just after, the researchers could isolate the effect of being eligible for the vaccine.

The circumstances, well-documented in the country's health records, were about as close to a randomized controlled trial as you could get without conducting one, Geldsetzer said.

The researchers looked at 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.

"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," Geldsetzer said. "They are similar to each other apart from this tiny difference in age."

The same proportion of both groups likely would have wanted to get the vaccine, but only half, those almost 80, were allowed to by the eligibility rules.

"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," Geldsetzer said.

Protection against dementia

Over the next seven years, the researchers compared the health outcomes of people closest in age who were eligible and ineligible to receive the vaccine. By factoring in actual vaccination rates -- about half of the population who were eligible received the vaccine, compared with almost none of the people who were ineligible -- they could derive the effects of receiving the vaccine.

Source: ScienceDaily

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