A study recently published in the journal Natural medicine observed that the recombinant shingles vaccine is associated with a reduced risk of dementia.

The varicella zoster virus is a herpes virus that causes shingles and chickenpox. In many countries, vaccination is recommended for older people due to the negative consequences of shingles. In addition, the protective effect of vaccination against dementia has been extensively studied. However, most studies compared unvaccinated and vaccinated cohorts, leading to selection and bias against healthy vaccinated individuals.

In particular, one study comparing people under and over the minimum age reported that a live shingles vaccine could potentially protect against dementia. However, the effect was limited to live vaccines and was only observed in women. The live vaccine was discontinued in the United States (US), and several countries followed suit in favor of the recombinant vaccine. Whether the recombinant shingles vaccine protects against dementia is unknown.

Newsflash: The recombinant shingles vaccine is associated with a lower risk of dementia. Image credit: BlurryMe / Shutterstock

About the study

The present study examined the associations between recombinant shingles vaccination and the occurrence of subsequent dementia, taking advantage of a natural opportunity presented by the non-use of the live shingles vaccine and the rapid acceptance of the recombinant vaccine after October 2017.

Electronic health record data were used from a network comprising 62 healthcare organizations with over 100 million patients. Demographic, diagnostic, and medication data were available. The primary cohort included all patients who received their first shingles vaccination between November 2017 and October 2020 at age ≥ 65 years. The comparison cohort included those vaccinated between October 2014 and September 2017.

Patients were excluded if they had a diagnosis of vascular dementia, unspecified dementia, Parkinson’s disease, or any other neurodegenerative disease before or (≤ 1 month) after vaccination. Cohorts were matched using propensity score matching for covariates such as sociodemographics, influenza vaccination history, comorbidities, and herpes infection history. The primary outcome was first dementia diagnosis three months to six years after vaccination.

Secondary outcomes were all-cause mortality, herpes zoster infection, a composite of death or dementia, and any dementia subcategory. The incidence of outcomes was calculated using the Kaplan-Meier estimator. The restricted mean time lost (RMTL) ratio was calculated and absolute differences in RMTL were converted into additional days without diagnosis (dementia) among those affected.

A permutation test assessed moderation by sex. Various secondary analyses were conducted after 1) stratifying by sex, 2) restricting exposure windows to six months before and after October 2017, 3) restricting cohorts to recipients of the predominant vaccine during each exposure window, 4) excluding those who received both vaccines, 5) restricting follow-up to 18 months, and 6) adjusting for socioeconomic deprivation.

Results

In total, the primary and comparison cohorts each comprised 103,837 people. They were followed up for an average of 4.15 and 6 years, respectively. Most (95%) of the primary cohort received the recombinant vaccine. Likewise, most people (98%) of the comparison cohort received the live vaccine.

The primary cohort had a lower risk of dementia over the next six years than the comparison cohort, meaning they lived 164 additional days (or 17% more time) without a dementia diagnosis. People vaccinated after October 2017 were less likely to develop herpes zoster infection in the six years following vaccination.

The results were significant for the combined outcome and there was no difference in all-cause mortality. In addition, the results were similar after limiting exposure windows to six months, restricting cohorts to those who received the predominant vaccine, excluding recipients of both vaccines, or adjusting for socioeconomic disadvantage.

The association between recombinant vaccine and dementia was evident in both men and women, with the effect being more significant in women. Likewise, the association with herpes zoster infection was evident in both sexes; there was no gender-specific attenuation. In addition, both vaccines were associated with a lower risk of dementia than tetanus, diphtheria, pertussis and influenza vaccines.

Conclusions

The recombinant shingles vaccine was associated with a lower risk of dementia over the next six years compared with a live shingles vaccine. The protective effect was higher in women. In addition, a 17% longer diagnosis-free time is clinically meaningful. Overall, the results provide a rationale for conducting a randomized controlled trial to confirm the results and determine the cost-effectiveness of the recombinant vaccine.