Two natural experiments in Canada suggest that herpes zoster (shingles or varicella zoster) vaccination averts or delays dementia diagnoses.

The analysis, published in The Lancet Neurology, was led by Stanford University researchers. The team estimated the effect of live attenuated shingles vaccination on new-onset dementia in 232,124 Canadians aged 70 years and older based on a natural experiment in Ontario. The researchers then triangulated the findings with a second natural experiment in Ontario and a quasi-experimental approach that used data from multiple provinces.

A quasi-randomized rollout of shingles vaccine took place in Canada in 2016. In Ontario, residents who turned 71 in or after January 2017 were eligible for free vaccination, while those who turned 71 before that month were ineligible.

“The date-of-birth eligibility thresholds of Ontario’s herpes zoster vaccination programme created three comparison groups: ineligible because they were born before Jan 1, 1945; eligible for only 3.5 months because they were born in 1945; and eligible for at least 1 year and 3.5 months because they were born between Jan 1, 1946, and Sept 15, 1951 (ie, aged 65–70 years on Sept 15, 2016),” the study authors wrote. 

Role of microbes in dementia 

Participants were born in Canada from January 1930 to December 1960 and registered with one of 1,434 primary care providers in the Canadian Primary Care Sentinel Surveillance Network as of September 2016. 

Dementia diagnoses were counted using electronic health records from January 1990 to June 2022, and Ontario residents aged 65 years and older were surveyed to estimate shingles vaccine coverage.

Targeting herpesviruses through vaccination might be a particularly effective approach because the immune system is thought to be crucial in the development of dementia.

The investigators also used synthetic difference-in-differences and a synthetic control method to compare trends in dementia rates before and after the start of the shingles vaccination program among eligible birth cohorts in Ontario with ineligible birth cohorts in other provinces.

Microbes have long been thought to be involved in the development of dementia, the researchers noted. 

“Targeting herpesviruses through vaccination might be a particularly effective approach because the immune system is thought to be crucial in the development of dementia,” they wrote. “Indeed, vaccines, especially those that are live-attenuated, often show broader health benefits beyond their intended target. The only vaccine in clinical use against a neurotropic herpesvirus is the herpes zoster vaccine.”

Need for mechanistic research

Being born immediately before, rather than immediately after January 1946, was tied to a lower likelihood a new dementia diagnosis by an absolute difference of 2.0 percentage points over 5.5 years of follow-up. Using a January 1945 threshold, dementia diagnoses were also 2.0 percentage points lower over the same period. 

After the shingles vaccine program began, new dementia diagnoses among people eligible for shingles vaccination in Ontario were significantly less common than in similar groups in other provinces without such a program.

“This analysis of natural experiments provides evidence, which is more likely to reflect a causal relationship than previous evidence from more standard observational data analyses, that herpes zoster vaccination prevents or delays incident dementia,” the authors wrote. “Mechanistic research into this effect could provide insights into the pathophysiology of dementia and maintenance of neuroimmune health in older age.”

In a related commentary, William McEwan, PhD, and David Hunt, MB BChir, PhD, both of Edinburgh University in Scotland, said that further evidence could help increase shingles vaccine uptake.

“The potential benefits of varicella zoster virus vaccination in preventing dementia are not formally communicated in the benefit–risk analysis, but with further evidence the benefits could become an important consideration in decisions to vaccinate, and part of a wider effort to use vaccination as a global strategy to promote healthy ageing,” they wrote.