New Level of Evidence Ties Shingles Vax to Lower Dementia Risk

New research suggests that the shingles vaccine Zostavax may protect against dementia, supporting the theory that viruses that affect the nervous system may contribute to neurodegeneration. 

The study, which leveraged a unique vaccine rollout policy in Wales and analyzed the health records of more than 280,000 older adults, showed that receipt of the live-attenuated shingles vaccine reduced the probability of developing dementia by around one fifth over 7 years. 

“Shingles vaccination is recommended for older adults. If the shingles [vaccine] has a benefit for dementia delay or prevention in addition to its preventive benefit for shingles, then this is all the more reason to get vaccinated,” study investigator Pascal Geldsetzer MD, PhD, MPH, Departments of Medicine and Epidemiology and Population Health, Stanford University in California, told Medscape Medical News. 

The study was published online on April 2 in Nature. 

‘A Different Level of Evidence’ 

Prior studies have suggested a potential link between the shingles vaccine and a lower risk for dementia. 

A “critical limitation” of this previous research is that the health behaviors of those who get vaccinated are different from those who do not. 

“Our study takes a fundamentally different approach and, thus, provides a very different level of evidence,” Geldsetzer said. 

The researchers took advantage of the fact that, in Wales, eligibility for the live-attenuated varicella zoster vaccine was determined on the basis of an individual’s exact date of birth. Those born before September 2, 1933, were ineligible and remained ineligible for life, whereas those born on or after September 2, 1933, were eligible for at least 1 year to receive the vaccine. 

“This is just like a randomized trial. We have a vaccine-eligible and a vaccine-ineligible group for which we know that they should be, on average, similar to each other, and therefore good comparison groups, because all that’s different about these two groups is if they were born a few days earlier or a few days later,” Geldsetzer explained. 

The electronic health record data showed that the percentage of adults who received the zoster vaccine increased from 0.01% among patients who were merely 1 week too old to be eligible, to 47.2% among those who were just 1 week younger. 

“We see in our data that just a 1-week difference across this date-of-birth cutoff means that you go from essentially no one getting vaccinated to about half of the population getting vaccinated,” said Geldsetzer.

Using these comparison groups, the researchers found that receiving the zoster vaccine, vs not receiving the vaccine, reduced the probability of a new dementia diagnosis over 7 years by 3.5 percentage points, corresponding to a 20% relative reduction. 

This protective effect was more pronounced in women, potentially due to stronger vaccine-induced immune responses or higher shingles prevalence.

The researchers replicated their findings in health records from other countries, including England, Australia, New Zealand, and Canada, which had similar rollouts of the zoster vaccine. 

“We just keep seeing this strong protective signal for dementia in dataset after dataset,” Geldsetzer said in a Stanford University news release. 

Geldsetzer has set his sights on a large, randomized controlled trial of the potential neuroprotective effects of the live-attenuated zoster vaccine, “which is the vaccine for which we have generated our compelling body of evidence.”

“It would be a very simple, pragmatic trial because we have a one-off intervention that we know is safe,” Geldsetzer said. He is seeking philanthropic funding for the trial as the live-attenuated vaccine is no longer manufactured by pharmaceutical companies.

It is unknown whether the newer version of the vaccine (Shingrix) may have a similar or greater impact on dementia, the researchers said.

‘Profound Implications’ 

“Although it is still unclear precisely how herpes zoster vaccination lowers the risk of dementia, the implications of the study are profound,” Anupam Jena, MD, PhD, with Harvard Medical School and Massachusetts General Hospital, Boston, wrote in a Nature News & Views. 

“The vaccine could represent a cost-effective intervention that has public health benefits strongly exceeding its intended purpose. Given the substantial economic and social burden of dementia, policymakers and health-care providers might need to reassess the value of widespread herpes zoster vaccination, particularly in older adults,” Jena added. 

Reached for comment, Courtney M. Kloske, PhD, Alzheimer’s Association director of scientific engagement, noted that the study supports research presented at the Alzheimer’s Association International Conference in 2020, which showed that flu and pneumonia vaccinations — especially multiple vaccinations over time — were associated with a lower risk for Alzheimer’s disease, as previously reported by Medscape Medical News. 

“This new study adds to our current knowledge by suggesting the shingles vaccine may also reduce someone’s risk of developing dementia,” Kloske said.

“These new results, while preliminary, call for further studies in large, diverse study populations to inform public health strategy regarding whether vaccinations can decrease our risk of developing dementia as we age,” Kloske added. 

“Big picture,” said Kloske, “these studies emphasize the importance of taking care of your overall health and highlight how important it can be in reducing the long-term risk of developing dementia.”

The study received funding from The Phil & Penny Knight Initiative for Brain Resilience, the National Institute on Aging, the National Institute of Allergy and Infectious Diseases, and Chan Zuckerberg Biohub. Geldsetzer, Jena, and Kloske reported no relevant disclosures.