A clever natural experiment in Canada suggests a routine shingles vaccine may do more than prevent rash. Instead, the vaccine could help delay the onset of dementia in later life.
Study: Herpes zoster vaccination and incident dementia in Canada: an analysis of natural experiments. Image credit: uganov Konstantin/Shutterstock.com
A recent study in Lancet Neurology investigated whether eligibility for a live attenuated herpes zoster (shingles) vaccine influenced dementia diagnoses among people aged 70 years and older, using estimates from cohorts born close to the strict eligibility cutoffs, living in Ontario, Canada. The researchers validated these findings using data from multiple Canadian provinces.
Exploring the Role of Microbes in Dementia
Scientists have long suspected that microbes, particularly neurotropic herpesviruses, may contribute to dementia. These viruses target the nervous system and become more likely to reactivate as people age, sometimes causing brain inflammation.
Research shows herpesviruses can trigger harmful changes in the brain. In mice, they promote the buildup of β-amyloid, a protein linked to Alzheimer’s disease. In lab-grown human brain tissue and cells, they increase tau phosphorylation, another hallmark of dementia.
Given the immune system's role in dementia, herpesvirus vaccines may offer unique protection. Live attenuated vaccines often deliver unexpected health benefits beyond their original target. Previous research has consistently highlighted that vaccinated people have lower dementia rates. Similar patterns have emerged with other vaccines as well, including the influenza vaccination, suggesting that vaccines might protect the brain through broader, pathogen-independent immune system effects, rather than by targeting specific pathogens.
Currently, the shingles vaccine, or herpes zoster vaccine, is the only vaccine in clinical use against a neurotropic herpesvirus. Most studies have compared vaccinated and unvaccinated individuals, but this approach has limitations. People who choose vaccination often differ in diet, exercise, and other lifestyle factors that affect dementia risk. These studies may not reflect the vaccine's true effect on the general population.
A Natural Experiment in Ontario
In 2016, Ontario launched a public herpes zoster vaccination program using a live attenuated vaccine, Zostavax, with a strict birthday cutoff, where people who turned 71 after January 1, 2017, were eligible for the free vaccine, while those who turned 71 before that date were ineligible. This eligibility rule created two groups of people born just before and after the cutoff date, which were essentially identical except for vaccine access.
The current study compared dementia rates between these two groups in Ontario, and also compared Ontario's vaccine-eligible population with similar age groups in provinces without vaccination programs.
People born in 1945 were eligible for the vaccine for approximately 3.5 months, while those born on or after January 1, 1946, were eligible for at least 15 months. The researchers focused on the 1946 cutoff because it created a sharper contrast in vaccination rates and eligibility duration. They also analyzed the 1945 cutoff as a secondary comparison. The researchers tracked new dementia diagnoses over 5.5 years.
Herpes Zoster Vaccination Is Associated With Fewer Dementia Diagnoses
The study analyzed 232,124 Ontario patients from a network of primary care providers. The group was 54% female and 46% male, with participants born between 1930 and 1960. The regression discontinuity approach indicated that people eligible for the vaccine under the 1946 cutoff were 27.4 percentage points more likely to receive it than those just ineligible. However, using the 1945 threshold, the corresponding estimate was an increase of 13.9 percentage points, which was smaller and less precise.
Among patients born around the 1946 cutoff, 4.3% of vaccine-eligible people developed dementia compared to 5.3% of ineligible people over 5.5 years. The study observed that vaccine eligibility reduced dementia diagnoses by an absolute 2 percentage points over 5.5 years. This finding held up across multiple statistical tests and remained consistent when controlling for other health conditions and small residual age differences.
A secondary analysis using the 1945 cutoff yielded similar results, where vaccine eligibility reduced dementia diagnoses by approximately 2 percentage points, confirming the main findings. Interestingly, the vaccine's protective effect appeared stronger in women than in men; however, this difference wasn’t statistically significant.
People born just before and after the cutoff dates were similar in terms of health conditions, medication use, and socioeconomic status, confirming that the groups were comparable. The vaccine’s effect was specific to dementia, and it didn’t affect other common health conditions. Importantly, provinces without vaccination programs showed no comparable discontinuities in dementia diagnoses between the same birth cohorts.
During the 5.5-year follow-up period, 10,259 patients, 4.4%, died, and 20,654 patients, 8.9%, either died or received a dementia diagnosis. Time-to-event analyses revealed that vaccine-eligible individuals went significantly longer without developing dementia than those who were ineligible. This protective effect was consistent across both the 1945 and 1946 birth date cutoffs.
The survival curves revealed that the vaccine not only reduces the overall number of dementia cases but also suggests a delay in the timing of diagnosis among those who eventually develop it.
Before Ontario’s vaccination program launched, dementia rates in Ontario were similar to those in other provinces. After the program began, dementia diagnoses declined among vaccine-eligible cohorts relative to comparable age groups in provinces without vaccination programs.
Conclusions
By analyzing Ontario’s vaccination program, researchers observed a 2 percentage-point reduction in dementia diagnoses over 5.5 years and evidence consistent with a modest delay in disease onset. These findings suggest the live attenuated herpes zoster vaccine may become an important tool for preventing or delaying dementia in older adults, while opening new avenues for understanding how the immune system influences brain health.
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