Immunization Update
Sonya Collins
A large observational study published October 2025 in Nature Medicine adds to growing evidence that reactivation of varicella-zoster virus (VZV)—the virus that causes shingles—may play a role in dementia risk later in life. These findings have implications for how pharmacists counsel patients about shingles vaccination, including older adults who’ve had shingles and those who previously received Zostavax, which is no longer recommended or available in the United States.
“This is one of a whole series of studies now in which the risk of dementia seems to be reduced or at least postponed in people who get the vaccine,” said William Schaffner, MD, a professor of preventive medicine at Vanderbilt University School of Medicine in Nashville, TN. “If you had any concern about the vaccine, this ought to be an additional motivator that you should get it.”
Findings
Researchers analyzed the EHRs of more than 100 million U.S. adults aged 50 years and older, controlling for nearly 400 demographic, clinical, and health care–seeking variables. They found that recurrent shingles was associated with a higher risk of dementia than a single shingles episode.
Vaccination against shingles, compared with an active control vaccine (pneumococcal polysaccharide vaccine), was associated with a lower risk of dementia. Protection against dementia waned over time with the older live-attenuated shingles vaccine (Zostavax), in parallel with waning protection against shingles itself. Adults who received two doses of the recombinant shingles vaccine (Shingrix) had a lower dementia risk than those who received only one dose. The association was strongest in populations already at higher risk for shingles, including older adults and women.
The study does not suggest that shingles
vaccines prevent dementia directly. Instead, the authors emphasized, preventing shingles—and therefore preventing repeated inflammatory and viral insults on the body—may reduce or delay dementia risk.
“If you’re not getting herpes zoster, the kind of inflammatory insults that might result in Alzheimer’s disease and dementia are not happening, so you’re preventing something from happening in the brain that might lead to dementia,” said Kenneth Schmader, MD, a geriatrician and professor of medicine at Duke University School of Medicine. His research focuses on herpes zoster infection and vaccines in older adults.
Link between shingles and dementia
The exact mechanism that links shingles and dementia is still unclear.
“Over time, the inflammatory hypothesis has gained more and more traction,” Schmader said.
Inflammation is believed to play a role in the accumulation of tau and amyloid b, which are hallmarks of Alzheimer disease. “It’s not a big stretch to think, ‘Here’s a big inflammatory insult with herpes zoster and VZV.’ ”
It is also well established, he added, that viruses including herpes simplex virus and VZV lie dormant in nerve cells in the brain.
Counseling patients
For pharmacists, the central message remains unchanged: The primary reason to recommend Shingrix is to prevent shingles and its complications, including severe pain and postherpetic neuralgia. However, the accumulating dementia data may resonate with patients who are hesitant.
Here are a few finer points to consider:
- Patients who previously received Zostavax should still receive the recombinant Shingrix vaccine, according to existing recommendations. Pharmacists should keep this in mind when counseling adults in their 70s and 80s who may believe they are already protected.
- Patients who’ve already had shingles can still benefit from the vaccine to prevent recurrence. It’s typically recommended patients get vaccinated a year after having shingles.
- The vaccine is preventive, not therapeutic, but it will help reduce risk of future episodes.
This large observational study strengthens the case that VZV reactivation is a modifiable risk factor for dementia, while reinforcing the value of shingles vaccination—particularly the recombinant vaccine—in older adults. For pharmacists, it provides another evidence-based talking point to support vaccine counseling, while stopping short of claims that vaccination directly prevents dementia. ■