Study Looks at Risk for Dementia After Shingles Vaccine in High-Risk Group

Older adults at higher risk for dementia were less likely to have a dementia diagnosis if they received a herpes zoster (shingles) shot, a cohort study using target trial emulation showed.

Among 500,000 people in skilled-nursing facilities for post-acute or long-term care, those who received the recombinant zoster vaccine (Shingrix) had a 24% lower risk of being diagnosed with dementia over 4 years compared with those not vaccinated (risk ratio [RR] 0.76, 95% CI 0.69-0.84), reported Kaleen Hayes, PharmD, PhD, of the Brown University School of Public Health in Providence, Rhode Island, and co-authors.

Receiving at least one zoster shot was tied to a cumulative 4-year dementia risk that was 5.81 (95% CI 3.9-7.5) percentage points lower — 18.8% versus 24.6% with no vaccine — Hayes and colleagues wrote in Annals of Internal Medicine.

Earlier studies had suggested a link between shingles vaccination and a lower risk of dementia in older adults. Some of that research focused on the live-attenuated zoster vaccine (Zostavax), which is no longer available in the U.S. For example, a “natural experiment” in Wales found that people who received the live vaccine had a 20% lower risk of dementia.

The FDA approved the recombinant zoster vaccine in 2017. A recent study of Medicare beneficiaries showed that receiving the recombinant zoster shot was associated with a lower risk of any dementia type, including Alzheimer’s disease and vascular dementia.

“Our research is the first to our knowledge to specifically study the newer, more effective vaccine in a modern-day population of older adults entering skilled-nursing care,” Hayes said.

“These folks are at high risk of both shingles and dementia, have been excluded from trials, and have historically had low uptake of the vaccine. So, evidence on the benefits of vaccination is especially key to support use of the vaccine in this population,” she told MedPage Today.

Mechanisms underlying possible relationships between the shingles vaccine and dementia risk are unclear. Last year, a study of U.S. patients linked AS01-adjuvanted vaccines for two different pathogens — the respiratory syncytial virus vaccine (Arexvy) and the recombinant zoster vaccine — to a lower incidence of dementia. That finding led some researchers to speculate that the adjuvant, which stimulates the immune system, may play a role.

“We don’t know with certainty why the risk of dementia is lower with shingles vaccination, but we have a lot of ideas. The most obvious factor is through the reduction of shingles infections, which cause neuroinflammation and increase the risk of stroke,” Hayes observed.

“There are also emerging hypotheses that vaccination in general, particularly those that have really robust immune activation, might be the protective mechanism here,” she added.

In their study, Hayes and colleagues emulated a randomized trial using a clone-censoring weight approach to compare dementia risk among people who received at least one shingles vaccine dose within 12 months of admission to a skilled-nursing facility versus those who did not receive the vaccine in this time frame. The researchers followed participants for up to 4 years until they had an incident dementia outcome, disenrolled in Medicare, or died.

Participants were Medicare fee-for-service beneficiaries ages 66 and older who were admitted to a skilled-nursing facility from 2017 through 2022. None had a dementia diagnosis at baseline and all were eligible to receive the recombinant zoster vaccine.

The cohort included 509,926 participants with a mean age of 79. Of these people, 1.73% received at least one vaccine dose in the 12 months after admission, most often after discharge (87%).

The association between the recombinant zoster vaccine and dementia was weaker in men (RR 0.82, 95% CI 0.68-1.01) than women (RR 0.75, 95% CI 0.67-0.84). It was attenuated in people who previously had a live shingles shot (RR 0.86, 95% CI 0.65-1.09) versus those who did not have a live zoster vaccine (RR 0.75, 95% CI 0.67-0.84), the researchers noted.

The study highlights the low uptake of the zoster vaccine, even among older adults with a skilled-nursing facility stay who are likely at high risk for herpes zoster as well as dementia, Hayes and co-authors noted. The CDC recommends the shingles shot for healthy adults ages 50 and up, and for people 19 and older with weakened immune systems.

Residual confounding — including “healthy vaccinee bias” — may have influenced outcomes, Hayes and colleagues acknowledged. Measurements of vaccine uptake and dementia were imperfect, they added.