Shingles vaccination associated with decreased mortality and morbidity in dementia patients

Managed care approaches seldom address how infectious disease prevention relates to neurodegenerative care. Yet, emerging evidence suggests that herpes zoster (shingles) vaccines may play a broader role in slowing cognitive decline. A recent study published in Cell provided strong evidence that herpes zoster (HZ) vaccination not only reduces the risk of dementia onset but also slows progression among patients already living with dementia.

Dementia remains one of the most pressing public health challenges, with rising prevalence and limited disease-modifying therapies. Current care models focus on symptomatic management, caregiver support, and mitigation of comorbidities. However, the biological underpinnings of dementia, particularly the role of neuroinflammation, have prompted exploration of novel preventive strategies. Neurotropic herpesviruses, including herpes zoster virus, persist in the nervous system and reactivate with age, potentially accelerating neurodegenerative processes. Prior studies pointed at a link between shingles vaccination and reduced dementia incidence, but concerns about confounding limited their credibility.

Building off past research in Wales and Australia, Pascal Geldsetzer, M.D., Ph.D., an assistant professor of medicine in the Division of Primary Care and Population Health at Stanford University, and the team leveraged a unique natural experiment in Wales, where strict date-of-birth eligibility rules for the live-attenuated HZ vaccine (Zostavax) created quasi-randomized cohorts. Individuals born just after September 2, 1933, were eligible for vaccination, while those born just before were not. This design allowed researchers to isolate the causal effect of vaccination on cognitive outcomes.

The analysis focused specifically on both ends of the disease spectrum. new diagnoses of mild cognitive impairment (MCI) among individuals with no prior cognitive impairment, and deaths due to dementia among diagnosed patients

The study’s findings supported earlier observations by Geldsetzer. Among individuals without prior cognitive impairment, HZ vaccination reduced new diagnoses of mild cognitive impairment over nine years, showing an estimated 3.1% reduction in new diagnoses of MCI. Among those already living with dementia, vaccination reduced deaths attributed to dementia, a 29.5%-point reduction. This protective effect on primary dementia mortality also translated to an overall benefit, showing an approximately 23 percentage point reduction in all-cause mortality among patients with baseline dementia diagnoses

Exploratory analyses suggested that these protective effects were not confined to a specific dementia subtype. In other words, vaccination appeared to act across the entire clinical disease course, from delaying early impairment to slowing late-stage decline.

According to Geldsetzer, “If the shingles vaccine really prevents or delays dementia, and, with this new study, also appears to have benefits for those who already have dementia, then this would be a hugely important finding for clinical medicine, population health, and research into the causes of dementia…. For the first time, we now have evidence that likely shows a cause-and-effect relationship between shingles vaccination and dementia prevention and treatment.”

While managed care organizations invest heavily in early detection and supportive services, there are few scalable interventions that alter disease trajectory. Pharmacologic options remain limited, costly, and often controversial in terms of efficacy. The idea that a widely available vaccine could reduce incidence and mortality could represent a paradigm shift.

Geldsetzer has plans to build on his research with a clinical trial. “I'm currently trying to raise funds to conduct such a trial from private and philanthropic foundations because we want to trial the live-attenuated vaccine (which is the vaccine for which we have generated our compelling body of evidence), which is off-patent…such a trial would definitively test if shingles vaccination prevents or delays dementia.”