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Photo Composite Credit: Jeffrey C. Chase
Scientific Frontline: Extended "At a Glance" Summary: Shingles Vaccination and Dementia Risk
The Core Concept: Receiving the shingles vaccine to prevent the reactivation of the Varicella zoster virus is associated with a significantly reduced risk of developing dementia in older adults. An epidemiological study observed up to a 24% lower risk of dementia over four years among vaccinated nursing home residents.
Key Distinction/Mechanism: While the primary purpose of the vaccine is to prevent shingles and direct complications like severe nerve pain, it indirectly protects brain health by interrupting a complex causal chain. By stopping the initial viral reactivation, the vaccine may prevent subsequent strokes, which are a major physiological trigger for cognitive decline.
Origin/History: Led by Daniel Harris at the University of Delaware and recently published in the Annals of Internal Medicine, this longitudinal study analyzed electronic health record (EHR) data from more than 500,000 nursing home residents.
Major Frameworks/Components:
- Target Trial Emulation: An advanced epidemiological design method that mimics a randomized trial using real-world health data to minimize selection bias.
- Negative Control Analysis: An analytical strategy adapted from the laboratory sciences to detect and adjust for residual bias, such as the tendency for healthier individuals to seek vaccination.
- Longitudinal Data Analysis: The utilization of extensive EHR databases to track patient outcomes and establish correlations across a multi-year period.
Branch of Science: Epidemiology, Immunology, and Neurology.
Future Application: Researchers plan to use similar real-world databases to investigate whether the shingles vaccine directly prevents stroke, aiming to map the complete physiological pathway between viral reactivation, stroke, and dementia. This analytical methodology could also inform future public health campaigns emphasizing the secondary preventative benefits of vaccines.
Why It Matters: With no cure currently available for dementia, identifying preventative measures is highly critical. Demonstrating that a well-tolerated vaccine can reduce the risk of severe cognitive decline provides a powerful, accessible tool to protect aging populations from debilitating neurological diseases.
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| Daniel Harris, assistant professor of epidemiology, is using electronic health record data to study the risk of dementia and stroke in older adults in long-term care settings who received the shingles vaccine. Photo Credit: Evan Krape |
A new study led by Daniel Harris, assistant professor of epidemiology, found that older adults in nursing homes who received the shingles vaccine had a 25% lower risk of developing dementia than those who were not vaccinated.
Nearly all adults aged fifty and older were infected with Human alphaherpesvirus 3, commonly known as the varicella-zoster virus (VZV), as children. VZV, the virus responsible for chickenpox, lies dormant in the nervous system for decades and can reactivate later in life as herpes zoster (shingles), causing a painful, blistering rash.
Previous studies have shown that people who develop shingles face about a 20% higher risk of cognitive decline, including dementia.
A new study led by Daniel Harris, assistant professor of epidemiology at the University of Delaware College of Health Sciences, found that older adults who received at least one dose of the shingles vaccine had a 24% lower risk of developing dementia over four years compared to those who were unvaccinated. The research was recently published in the Annals of Internal Medicine, one of the nation’s leading peer-reviewed medical journals.
The two-year, investigator-initiated study was supported by funding from GlaxoSmithKline, which manufactures the shingles vaccine, and involved collaborators at Brown University, the Providence VA Medical Center, and Rhode Island Hospital.
In the longitudinal study, Harris analyzed electronic health record (EHR) data from more than 500,000 people admitted to nursing homes served by PointClickCare. Using these data, he examined whether receiving the shingles vaccine within twelve months of admission or discharge was associated with a lower risk of dementia.
Only about 8,000 of the more than 500,000 people in the study chose to receive the shingles vaccine, with most vaccinations occurring after discharge from a skilled nursing facility.
“While the final number of people who got vaccinated was quite small at 8,000, it’s still larger than most trials,” Harris noted.
Because people who choose to be 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 laboratory 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.
These findings, however, 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,” he added.
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 ten years after the initial infection. Measles vaccines prevent that from happening.”
Connecting the Dots
In future research, Harris plans to use these 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 is 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.”
Previous study: Herpes zoster and long-term risk of subjective cognitive decline
Published in journal: Annals of Internal Medicine
Authors: Kaleen N. Hayes, PharmD, PhD, Daniel A. Harris, PhD, Kevin W. McConeghy, PharmD, PhD, Lexie R. Grove, PhD, Richa Joshi, MBA, Lisa Han, MPH, H. Edward Davidson, PharmD, Preeti Chachlani, MA, Thomas A. Bayer, MD, Mriganka Singh, MD, Yasin Abul, MD, Frank DeVone, MS, and Stefan Gravenstein, MD
Source/Credit: University of Delaware | Amy Cherry
Edited by: Scientific Frontline
Reference Number: epi081126_01
