Shingles vaccine may directly guard against dementia, study hints

The shingles vaccine may prevent or delay dementia, compelling new data suggest.

In a study published April 23 in the journal JAMA, researchers analyzed electronic health records from across Australia. They found that older adults who were eligible for a free shingles vaccine were significantly less likely to be diagnosed with dementia over the following 7.4 years than those who were slightly too old to qualify for the vaccination program.

These findings support the "viral hypothesis" of Alzheimer's disease, which posits that viral infections contribute to the development of the condition, which is the most common form of dementia. Specifically, the hypothesis points to herpesviruses, a family of viruses that includes varicella-zoster virus, the germ behind chickenpox and shingles.

If confirmed by additional research, the results of the new study suggest that an effective and low-cost tool for reducing dementia risk may already exist.

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"It is very hard to see how anything other than the vaccine could explain the strong protective effect" observed in the study, Dr. Sten Vermund, dean of the University of South Florida College of Public Health, who was not involved in the work, told Live Science in an email.

A pseudo-clinical trial

If a person contracts chickenpox, the varicella-zoster virus can remain dormant in the nervous system for decades before reactivating later to cause shingles, a condition marked by a painful rash. The ability to fall latent and then "reawaken" in the body is a core characteristic of herpesviruses.

The shingles vaccine helps to build immunity and prevent reactivation of the virus, and it's thus highly effective at preventing shingles and its complications, such as long-term nerve pain, vision loss and a higher risk of bacterial skin infections.

Previous studies found that older people who have been vaccinated against shingles tend to have lower rates of dementia than those who have not received the shingles vaccine. But these studies had a major caveat: People who choose to get vaccinated also tend to be more health-conscious and more likely to eat well and exercise regularly — habits that also help protect against dementia. So, while past research showed a correlation between shingles vaccination and reduced dementia risk, it couldn't prove that one caused the other.

The gold-standard test to see whether the vaccine actually protects against dementia would be to conduct a large clinical trial, in which participants would be randomly assigned to receive the vaccine or a placebo. But such trials are costly, and in this case, could potentially pose ethical issues.

"It would be nice to see a randomized and controlled study, showing placebo versus herpes vaccine, rather than a retrospective observational as this study was," said Dr. Logan DuBose, co-founder of Olera.care, a caregiver support platform for senior care needs. "However, there might be some ethical issues with giving some people the vaccine and others not" — given it's known to be effective against shingles — "making that a hard study to conduct," DuBose, who was not involved in the work, told Live Science in an email.

The new study took a different approach. "What's so special about our study is that we take advantage of a very similar scenario to a randomized trial," senior author Dr. Pascal Geldsetzer, an assistant professor of medicine at Stanford University, told Live Science in an email.

Australia launched a shingles vaccination program on Nov. 1, 2016, providing a unique opportunity for a quasi-experimental study. The program offered a free shingles vaccine to adults ages 70 to 79. Those who turned 80 just before the program began were ineligible, while those who turned 80 just afterward were eligible.

As in a clinical trial, "we have a vaccine-eligible and a vaccine-ineligible group for which we know that they should be on average similar to each other, and therefore good comparison groups," Geldsetzer said. "All that's different about these two groups is if they were born a few days earlier or a few days later."

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A decrease in dementia risk

The researchers analyzed data from over 101,200 individuals across 65 general medical practices in Australia, focusing on those born just before and after Nov. 2, 1936 — the cutoff birthday for vaccine-program eligibility. The difference in vaccination rates between these two cohorts was substantial, with eligibility boosting the likelihood of receiving the vaccine.

Over a 7.4-year follow-up period, the rate of dementia among eligible individuals was 1.8 percentage points lower than that of ineligible people. Overall, 3.7% of the eligible individuals were diagnosed with dementia, compared to 5.5% of ineligible individuals.

This effect was not observed for other chronic conditions, such as high blood pressure, heart disease or diabetes, suggesting that the shingles vaccine had a specific protective effect against dementia. The analysis also showed no increase in diagnoses of other common chronic conditions, or use of other preventive services — like cancer screening or annual flu vaccination — among those who were vaccine-eligible. This reinforced the idea that the difference in dementia was driven by the vaccine itself.

Previously, Geldsetzer and his team conducted a similar analysis of health records in Wales and found that the shingles vaccine was linked to a 20% lower rate of new dementia diagnoses among vaccinated individuals.

"My first thought [about the Australian study] was that there is a modest difference, being 1.8% less likely to get a diagnosis," DuBose said. However, having two well-designed studies that show the risk of dementia diagnosis is lower if you've had the vaccination is compelling, he said.

Limitations and next steps

DuBose noted that the study could have gone a step further by examining whether the vaccine's effect differed in people with different genetic backgrounds. For instance, a specific gene variant called APOE4 is linked to dementia. It could be that the vaccine's effects vary depending on a person's genetic background, he suggested.

More studies are needed to understand the mechanism behind the vaccine's protective effect against dementia, as that's currently unclear. One theory suggests that reactivation of the varicella-zoster virus may trigger brain damage through a range of mechanisms, including the buildup of abnormal proteins and chronic inflammation. By preventing reactivation, the shingles vaccine may theoretically prevent this brain damage.

Another hypothesis is that the vaccine provides protection not by targeting viruses directly but by tuning the immune system in a way that slows or alters the course of dementia.

Now, Geldsetzer and his team are seeking private and philanthropic funding to launch a formal clinical trial testing the shingles vaccine's ability to protect against dementia.