Researchers have uncovered the strongest evidence yet that the shingles vaccination may reduce the risk of developing dementia1. The work published in Nature last month, took advantage of a vaccination rollout that took place in Wales over a decade ago. The UK government dictated that from 1 September 2013, people born on or after 2 September 1933 were eligible for the “Zostavax” shot, while those born just before this date were not. The policy created a natural experiment whereby individuals born immediately before the eligibility cutoff date could be compared with eligible individuals born immediately after it. People born just a few weeks apart are unlikely to differ in any meaningful way, thus the fortuitous design practically eliminated confounding factors that have weakened prior investigations.
A significant reduction in dementia risk, especially for women
The researchers obtained the health records of 282,541 adults who resided in Wales and did not have a diagnosis of dementia when the country’s shingles vaccine program began. By 2020, one in eight older adults, who were by then 86 and 87 years of age, had been diagnosed with dementia. However, after accounting for the fact that only about half of those eligible for the vaccine received it, those who received the shingles vaccine were 20% less likely to be diagnosed with dementia over the next seven years than those who went without. The effect was especially marked among women.
The researchers conducted a separate analysis using death certificate data. It corroborated their initial conclusions, showing that eligibility for the shingles vaccine reduced dementia-related deaths by approximately 5% over nine years. The study also confirmed that, similar to clinical trials, the vaccine significantly reduced the occurrence of shingles by about 37%. However, the reduction in dementia risk could not be fully explained by a decrease in shingles cases alone. Scouring the data for other variables that could have affected dementia risk, the researchers found that both groups, vaccine-eligible and vaccine-ineligible, were virtually indistinguishable. There was no difference in education levels, preventive treatment uptake, or incidents of health conditions such as diabetes, heart disease, and cancer.
Broad Immune Boost Speculation
It is unclear how the shingles vaccines might protect against dementia. One theory is that it directly lowers dementia risk by reducing reactivation of the dormant varicella virus, thereby reducing nervous system inflammation. Another theory is that the vaccine indirectly confers neuroprotection by generating a widespread immune response that lowers inflammation, independently of any effect on the virus. Women tend to produce a stronger response to vaccinations, which could potentially explain the sex differences in the study. Moreover, the reduction in dementia incidence only became evident more than one-year post-vaccination, further supporting the theory of longer-term immune modulation.
While the findings are compelling, the researchers acknowledged several limitations. One challenge was the potential under-detection of dementia in health records. In the vaccinated group fewer people got shingles, hence limiting trips to the doctor that might have led to a dementia diagnosis. The study also focused on a specific age group, making it difficult to apply the results to younger populations.
Findings based on an outdated vaccine
Another consideration is that the study examined only the live-attenuated Zostavax vaccine, rather than the non-live Shingrix vaccine, which is slightly more effective at protecting against shingles and now the more commonly used. This is important, because it is the live-attenuated vaccines that are considered to have the broader effects on the immune system.
The study was an ingenious use of record and linkage data. Research is now turning its attention to see whether Shingrix can provide a similar benefit. The results are promising2. Given the widespread availability and safety profile of the shingles vaccine, if validated in other settings, the shingles vaccine could represent one of the most promising low risk and cost-effective preventive strategies for dementia.