Because people who choose to get vaccinated are often healthier, the researchers used a target trial emulation—a new design method in epidemiology that mimics a randomized trial using real-world health data—to reduce bias.

“We used analytic strategies to account for preexisting differences between individuals who received the vaccine versus those who did not, but we can only soak up what we can measure,” cautioned Harris. 

Researchers employed a method common in lab sciences – a “negative control” analysis – to assess the extent of any bias. Results from the negative control analysis reduced the estimated benefit of the vaccine, but vaccination remained associated with a 12% lower risk of dementia over four years. 

“There’s a lack of randomized trial evidence on the potential effects of the shingles vaccine on dementia risk, but there are methodological and analytical tools at our disposal to generate evidence in real-world databases; however, there are still threats to validity,” Harris said. 

However, the findings are consistent with previous studies conducted in the United Kingdom that have linked shingles vaccination with a lower risk of dementia. 

“The side effects of the vaccine are very low, and shingles can lead to serious complications like long-term nerve pain and vision loss.” 

Harris also hopes the work inspires more public health campaigns highlighting the benefits of vaccines. 

“Vaccines do more than help prevent the infection they’re originally intended to protect against,” said Harris. “They help prevent the consequences of infection.”

Harris points to COVID-19 and measles vaccines as real-world examples.

“Measles is not only deadly in childhood, but the virus can remain dormant in the brain and cause a severe and deadly neurological syndrome seven to 10 years after the initial infection. Measles vaccines prevent that from happening.” 

Connecting the dots 

In future research, Harris plans to use the data to investigate whether the shingles vaccine also helps prevent stroke. 

“It’s clear that if you get shingles, your risk of stroke is elevated in the months to one year after infection, especially if the virus reactivates near the eye,” Harris said. 

Stroke is also a major risk factor for dementia. 

“We know the vaccine helps protect against shingles; we know shingles increases stroke risk, and stroke is a major risk factor for dementia,” Harris said. “Now, we’re trying to connect all those dots to see how the pieces fit together.” 

He’s hoping to use the same EHR data to study the complex causal chain of events that could be stopped through infection prevention. 

“The stroke that can follow shingles may be what actually triggers the dementia,” said Harris. “If we can help prevent shingles, we can help prevent stroke, and that could, in turn, help prevent dementia.”