A recent study published in the journal Naturopathy 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 the elderly, given the adverse effects of shingles. Furthermore, the protective effect of vaccination against dementia has received considerable attention. However, most studies have compared unvaccinated and vaccinated cohorts, leading to selection and bias against healthy vaccines.
A study comparing people below and above the age limit found that the live shingles vaccine could protect against dementia. However, the effect was limited to live vaccines and was only observed in women. The live vaccine has been discontinued in the United States (US), and several countries followed suit in favor of the recombinant vaccine. Whether recombinant shingles vaccination protects against dementia is unknown.
About the study
The current study examined the associations between recombinant shingles vaccination and subsequent dementia incidence. They took advantage of a natural opportunity created by the discontinuation of the live shingles vaccine and the rapid uptake of the recombinant vaccine after October 2017.
Electronic health record data was used from a network that included 62 healthcare organizations and more than 100 million patients. Demographic, diagnostic, and medication data were available. The primary cohort included all patients who received their first shingles vaccine at ≥ 65 years between November 2017 and October 2020. The comparison cohort included those vaccinated between October 2014 and September 2017.
Patients were excluded if they were diagnosed with vascular dementia, unspecified dementia, Parkinson’s disease, or other neurodegenerative disease before or (≤ 1 month) after vaccination. Cohorts were matched on covariates, including sociodemographics, history of influenza vaccination, comorbidities, and history of herpes infections, using propensity score matching. The primary outcome measure was the first diagnosis of dementia three months to six years after vaccination.
Secondary outcomes included all-cause mortality, herpes zoster infection, combination of death or dementia, and any subcategory of dementia. The outcome incidence was calculated using the Kaplan-Meier estimator. The reduced mean time lost (RMTL) was calculated and the absolute differences in RMTL were translated into additional days (dementia) without diagnosis among those affected thereafter.
A permutation test evaluated moderation by gender. Several secondary analyzes were performed after 1) stratifying by sex, 2) limiting exposure periods to six months before and after October 2017, 3) restricting cohorts to recipients of the main vaccine during each exposure period, 4) excluding those who received both vaccines, 5) limiting follow-up to 18 months, and 6) adjusting for socioeconomic deprivation.
Findings
In total, the primary and comparison cohorts each consisted of 103,837 individuals. They were followed for an average of 4.15 and 6 years, respectively. The majority (95%) of the primary cohort received the recombinant vaccine. Similarly, most individuals (98%) in the comparison cohort were recipients of the live vaccine.
The primary cohort had a lower risk of dementia over the next six years than the comparison cohort, which translated into 164 additional days (or 17% more time) without a dementia diagnosis among those affected afterwards. People who were vaccinated after October 2017 were less likely to develop a herpes zoster infection six years after vaccination.
The results were significant for the composite outcome and there was no difference in all-cause mortality. Furthermore, results were similar after exposure periods were limited to six months, cohorts were limited to those who received the main vaccine, recipients of both vaccines were excluded, or recipients of both vaccines were excluded or adjusted for socioeconomic deprivation.
The association between recombinant vaccine and dementia was clear in men and women, although the effect was more significant in women. Similarly, the association with herpes zoster infection was found in both sexes; there was no moderation based on gender. In addition, both vaccines were associated with a lower risk of dementia than tetanus-diphtheria-whooping cough and influenza vaccines.
Conclusions
The recombinant shingles vaccine was associated with a reduced risk of dementia over the next six years compared to a live shingles vaccine. The protective effect was greater in women. Furthermore, 17% more time without diagnosis is clinically meaningful. Overall, the findings provide a rationale for conducting a randomized controlled trial to confirm the results and determine the cost-effectiveness of the recombinant vaccine.