Shingles Vaccine May Offer Dementia Prevention, Study Suggests

What if a dementia vaccine existed? A study published in Nature on April 2 by U.S. and German scientists suggests this may soon be a reality.

The varicella-zoster virus causes chickenpox and, later in life, shingles. Scientists have linked it to dementia because it infects the nervous system. Vaccines exist for both conditions. The chickenpox vaccine protects against the initial infection, while the shingles vaccine prevents the virus from reactivating in adults who were previously infected (most adults born before chickenpox vaccination became widespread in the late 1990s), thus preventing shingles.

Traditionally, determining if the shingles vaccine could prevent dementia would require a randomized controlled trial. This would involve dividing adults into two groups: a control group receiving no vaccine and an intervention group receiving the vaccine. Dementia rates would then be compared over time. However, dementia is a disease of old age, making such a trial difficult due to the need to track thousands of patients and collect data over many years.

The researchers behind this new study, including Markus Eyting and Pascal Geldsetzer of Stanford University, took a different approach by recognizing that such an experiment had already occurred unintentionally.

In 2013, Wales began offering the shingles vaccine to adults born on or after September 2, 1933, while those born earlier were ineligible. This meant that someone born on September 4, 1933, could receive the vaccine, while someone born just days earlier on August 28, 1933, could not.

Because birthdates around this cutoff are essentially random, the only significant difference between Welsh adults born just before and after the cutoff was their eligibility for the vaccine. This effectively randomized them into vaccinated and unvaccinated groups.

This type of accidental randomization is known as a natural experiment—science happening organically. These experiments occur frequently, but often go unnoticed until researchers analyze existing data.

After several years since the vaccination program began, researchers examined Welsh adult health records to identify dementia cases since 2013. The results were striking.

Almost no one born before the cutoff received the shingles vaccine, while about half of those born after the cutoff did. As expected, the vaccinated group had lower rates of shingles. Surprisingly, they also had a significantly lower rate of dementia diagnosis. Researchers estimated a nearly 20% reduction in dementia diagnosis among those who were vaccinated by chance.

While this analysis is compelling, it doesn’t explain exactly why the shingles vaccine might reduce dementia rates.

The most obvious explanation is that preventing viral reactivation with the vaccine reduces the risk of dementia if shingles predisposes individuals to the disease. The researchers found evidence supporting this. First, those with more shingles episodes had higher dementia rates. Second, those who received antiviral medication for shingles, which suppresses reactivation, had lower dementia rates compared to those who didn’t.

Another possibility is that the body’s response to the vaccine itself protects against dementia. Vaccines stimulate the immune system, and this response could theoretically affect the brain in a way that reduces dementia risk. Researchers found two pieces of evidence supporting this. First, those who recently received a flu vaccine when they received their shingles vaccine were even more protected against dementia. Second, women, who have different immune responses to vaccines than men, experienced a much larger protective effect against dementia.

Any of these mechanisms could explain the shingles vaccine’s potential protective effect against dementia. (One of us, Jena, explored these in depth in a published in Nature alongside the study.) Further research is needed to fully understand these findings, but this study provides a valuable framework for future investigation.

This understanding of the zoster vaccine, shingles, and dementia was made possible by researchers recognizing the conditions for a natural experiment in Wales and analyzing the data. In an age of extensive data collection, countless natural experiments in healthcare await discovery, provided researchers have the resources to find and analyze them.