Shingles Vaccine Lowers Dementia Risk

A recent study published in Nature Medicine looked into the impact of recombinant shingles vaccines on dementia.

Background

Varicella-zoster virus (VZV), also known as human herpesvirus 3, is the cause of chickenpox and shingles. Given the possibility for negative consequences from shingles, health officials in some countries recommend vaccine for elderly people.

Recent research indicates that the live herpes zoster (shingles) vaccine may protect against dementia. Most studies comparing vaccinated and unvaccinated populations are prone to selection and healthy vaccination biases.

Existing evidence is limited and only refers to the live herpes zoster vaccine, which was discontinued in the United States (US) and other countries; so, the efficacy of the recombinant shingles vaccine is questionable.

About the study

In this observational study, researchers looked into whether the recombinant shingles vaccine could reduce the risk of developing dementia. They also looked at the risk of dementia among shingles, influenza, and tetanus/diphtheria/pertussis (Tdap) vaccine recipients.

The researchers exploited electronic medical data and a natural experimental opportunity created in the United States by the rapid adoption of recombinant vaccinations and the subsequent discontinuation of live vaccines beginning in October 2017.

They analyzed patients who got shingles vaccinations after and before the step change to determine the relationships between recombinant vaccine exposure and eventual dementia incidence.

The researchers used propensity score-type matching (PSM) to account for differences in vaccinated population characteristics. They compared 103,837 people who received their initial shingles vaccination between November 2017 and October 2020 (95% recombinant vaccine recipients; median follow-up, 4.2 years) to the same number of people who received their initial vaccination between October 2014 and September 2017 (98% live vaccine recipients; median follow-up, 6.0 years).

The researchers calculated the restricted mean time lost (RMTL) and hazard ratios (HR) for analysis. They combined cohort-level follow-up horizons (main analysis) with matched individual pair-level data (coarsened exact matching analysis) as a supplementary analysis.

They also looked into gender-based differences in connections. They contrasted the results obtained by confining analysis to primary vaccine recipients, limiting exposure windows to six months on both sides of the step shift, and eliminating receivers of both vaccines using socioeconomic deprivation adjustments.

Results

Individuals who received the recombinant herpes zoster vaccine had a lower risk of developing dementia in the following six years (RMTL ratio of 0.8), resulting in 17% more diagnosis-free time or 164 additional days without dementia diagnosis among affected individuals.

With the exception of Lewy body and frontotemporal dementia, the connection was stable across dementia subtypes.

Furthermore, persons immunized after October 2017 had a considerably lower risk of having herpes zoster infections in the six years following immunization, with an RMTL ratio of 0.7.

Controlling for socioeconomic deprivation, restricting analyses to predominant vaccine receivers, limiting exposure periods to six months of step change sides, and omitting recipients of both vaccines produced similar results.

Furthermore, the researchers discovered similar risk differences by limiting follow-up to the period preceding the coronavirus disease in 2019 (COVID-19, HR, 0.7).

Using bootstrap or parametric variance estimates, they discovered comparable results when comparing primary analyses and coarsening exact-type matching for covariates such as age, race, biological sex, and neurological diseases.

The recombinant herpes zoster vaccination was also linked to decreased dementia risk than Tdap and influenza vaccines (RMTL ratios of 0.7 to 0.9).

The connection was detected in both males and females, however it was stronger in females than males (22% vs. 13% longer diagnosis-free duration). The team found connections with shingles in both men and women without regard for gender.

The mechanisms underlying the potential dementia protection given by shingles immunizations are unknown. One possible explanation is that it prevents herpes infection, which promotes dementia. This hypothesis has been debated for decades and may explain the reduced risk of dementia associated with both forms of herpes zoster vaccines.

The recombinant immunization gives higher protection, although its effectiveness diminishes over time. The recombinant vaccine contains immunostimulants, which may increase the risk of dementia. The observed HR values at the end of follow-up may imply that the immunization delays dementia onset; however, this is not well supported and needs to be replicated.

Conclusions

The study found that recombinant shingles immunizations had a lower incidence of dementia than live vaccines within six years.

This amounts to a 17% increase in time without a dementia diagnosis, which is a significant effect size, especially given that live shingles immunizations have also been linked to a lower risk of dementia. The discovery lends legitimacy to the research and has significant public health consequences.

The recombinant shingles vaccination demonstrated a 9.0% greater protective effect in females than in males, which is unrelated to women’s improved shingles protection.

This conclusion demands for more investigation and large-scale randomized controlled trials to confirm the vaccine’s potential further benefits. Non-observational designs should be used in future studies to determine the causality of associations.

For more information: Taquet, M., et al. (2024) The recombinant shingles vaccine is associated with a lower risk of dementia. Nature Medicine, doi:https://doi.org/10.1038/s41591-024-03201-5