What a U.S. Study Found About the Shingles Vaccine and Dementia

Older adults in the U.S. were less likely to develop dementia if they received the recombinant subunit zoster (shingles) vaccine (Shingrix), an analysis of 1.5 million Medicare beneficiaries showed.

The incidence of any type of dementia was 10.45 (95% CI 10.29-10.62) per 1,000 person-years for older adults who received the two-dose shingles vaccine and 15.73 (95% CI 15.57-15.89) per 1,000 person-years for contemporary comparators who were unvaccinated, reported Susan dos Reis, PhD, of the University of Maryland School of Pharmacy in Baltimore, and co-authors.

Over follow-up periods of 3 years or less, people who received the recombinant shingles vaccine had 33% less risk of any dementia type (HR 0.67, 95% CI 0.65-0.68), 28% less risk of Alzheimer’s disease (HR 0.72, 95% CI 0.69-0.74), and 33% less risk of vascular dementia (HR 0.67, 95% CI 0.64-0.70), dos Reis and colleagues wrote in Alzheimer’s & Dementia.

Over more than 3 years of follow-up, HRs were 0.74 (95% CI 0.69-0.79) for any dementia type, 0.83 (95% CI 0.74-0.94) for Alzheimer’s disease, and 0.66 (95% CI 0.57-0.78) for vascular dementia, they added.

This study is one of the first to evaluate the two-dose recombinant zoster vaccine in a large, representative Medicare sample with a contemporary comparator group, the researchers noted.

“The findings support the growing evidence from real-world data showing that the herpes zoster vaccine is associated with a lower risk of new-onset dementia,” dos Reis told MedPage Today. “Our study incorporated several rigorous sensitivity analyses, and we were pleased to report that the results were robust to the primary analysis.”

Many studies analyzing the relationship between the shingles vaccination and subsequent dementia were based on the live-attenuated zoster vaccine (Zostavax), which is no longer available in the U.S., dos Reis and co-authors pointed out.

A “natural experiment” in Wales and recent research in Canada, for example, both showed that dementia risk was lower with the live shingles vaccine. In 2024, researchers found that adults who predominantly received the recombinant zoster vaccine had a 17% increase in time without a dementia diagnosis compared with those who received the live vaccine.

Population-based studies support the hypothesis that vaccination against shingles might delay or prevent dementia, but more research is needed, observed Maxime Taquet, PhD, of the University of Oxford in England, who wasn’t involved with the Medicare analysis.

“The two most important steps toward understanding whether the vaccine has a protective effect are clinical trials to confirm the causal effect, and mechanistic studies to understand why the recombinant shingles vaccine may protect against dementia,” Taquet told MedPage Today.

In their analysis, dos Reis and colleagues followed older adults who received two doses of the recombinant zoster vaccine and a concurrent comparator group of people who were not vaccinated at the time of a routine preventive care visit to mitigate healthy-user bias. They matched one vaccine-exposed person to two unvaccinated people on age, sex, and race or ethnicity.

Participants were 65 or older at the time of the second vaccine dose or preventive care visit date, had been enrolled in fee-for-service Medicare parts A, B, and D for at least 11 months, and had no pre-existing dementia of any type. People enrolled in Medicare Advantage were excluded.

The cohort included 502,845 people who received both doses of the recombinant zoster vaccine and 1,005,690 unvaccinated comparators. In both groups, 60% of participants were female, 93% were white, and 55% were ages 70 to 79.

Dementia diagnoses were based on claims data. Findings were adjusted for medical comorbidities, prescription medications, healthcare utilization, and certain preventive vaccinations.

The results were robust to several sensitivity analyses that accounted for disease latency and prior exposure to tetanus, diphtheria, and pertussis (Tdap) and live shingles vaccines, dos Reis and colleagues stated.

The study had several limitations, they acknowledged. Dementia diagnoses may have been misclassified, and outcomes may have been influenced by variables like educational attainment, marital status, or physical activity, which the study could not measure.

Infections like herpes zoster may increase the risk of developing dementia, but evidence has been inconclusive, the researchers noted. “Despite the accumulating real-world evidence, further work is needed to evaluate if there is a causal association between recombinant zoster vaccine and reduced risk of dementia,” dos Reis said.