Eligibility of Shingles Vaccine Reduces Risk of Dementia in Older Adults

Eligibility of Shingles Vaccine Reduces Risk of Dementia in Older Adults

In a powerful natural experiment using Australian health data, researchers found that eligibility for the Beltrock vaccine can reduce dementia diagnoses and strengthen the case for preventive strategies in brain health.

In a recently published study in theJAMA (Journal of the American Medical Association)An international team of researchers determined whether eligibility for herpes zoster (HZ) (virus that causes shingles) vaccinations based on date of birth influenced the likelihood of receiving a new diagnosis of dementia (memory loss and thinking problems).

background

Dementia affects over 55 million people worldwide and represents a growing public health crisis. While age remains the strongest risk factor, infections can also play a role. There is an unmistakable connection between HZ and dementia. HZ results from reactivation of varicella-zoster virus, a neurotropic virus that can affect the central nervous system. Vaccination against HZ may not only prevent shingles but also a small risk of dementia, possibly through immune modulation. A previous quasi-experiment in Wales found this association, but replication is essential across different populations and health systems. Further research is needed to validate these results globally.

About the study

To ensure the finding was specific to dementia, researchers checked whether vaccine eligibility affected 15 other common conditions, such as heart disease or diabetes. It showed no significant impact on these diagnoses.

The present study used a quasi-experimental design that facilitated primary care delivery to 65 general practitioners across Australia using the health informatics pens. The analysis used a natural eligibility threshold created by the National Immunization Program, which on November 1, 2016, offered the live attenuation vaccine (Zostavax) free of charge to individuals aged 70 to 79 years. Eligibility was determined by date of birth: people born on or after November 2, 1936 were eligible, while those born before were not. This setup allowed a comparison between groups that were nearly identical in age and baseline health and differed primarily in vaccine access.

Patient records included diagnostic history, vaccinations, prescriptions, and demographic details. Birth dates were coded weekly and all diagnoses, including dementia, were identified using open text fields provided by GPs. Patients aged 50 years or older as of November 1, 2016 and with at least one clinical visit between 1993 and 2024 were included.

The primary outcome was the first recorded diagnosis of dementia during 7.4 years of follow-up. The main burden was eligibility for HZ vaccination based on date of birth. Statistical analysis focused on regression discontinuity (RD) and compared individuals born just before and after the eligibility threshold. This method controls for both observed and unobserved variables assuming no abrupt changes other than vaccination status. Secondary analyzes used time-to-event models, including accelerated failure time and Kaplan-Meier survival analyses, as well as robustness checks across multiple bandwidths and modeling strategies. All analyzes were performed using R statistical software.

It is important to note that the effect measured in this study is for eligibility for HZ vaccination and not for confirmed receipt of the vaccine, as vaccination status is likely subject to the primary care data used. Because of this underreporting, the study authors did not attempt to estimate the impact of not receiving the vaccine, as this could overstate the results.

In addition, the study population was drawn from practices that agreed to participate and use the Pencs platform, so the data is not fully representative of all Australian primary care patients. The effect estimate is also “local” and applies most clearly to individuals who were approximately 79 to 80 years old at the time the HZ vaccination program began.

The protective effect observed in this study is specific to the live Hz vaccine (Zostavax), as the newer recombinant vaccine (Shingrix) was not widely available in Australia during the study period.

Study results

The study confirmed that the effect was not just a statistical fluke associated with year, as the same analysis method on birth dates in surrounding years (1933-1935, 1937-1939) found that only the actual vaccine eligibility date of 1936 showed a significant association with lower dementia rates.

Data from 101,219 patients were analyzed, focusing on 18,402 patients born within 482 weeks of the November 2, 1936, eligibility threshold. The average age in this subgroup was 77 years, with 54.3% of participants being women. The likelihood of receiving the HZ vaccine increased from 6.5% among ineligible individuals to 30.2% among eligible individuals, confirming that the government date effectively differentiated vaccine exposure.

Importantly, no differences were observed in prior health status, receipt of other preventive services, or dementia risk factors above the eligibility threshold to support the validity of the natural experiment. Regression discontinuity analysis showed that eligibility for Hz vaccination resulted in a statistically significant reduction of 1.8 percentage points in the probability of a new dementia diagnosis over 7.4 years (95% confidence interval: 0.4 to 3.3; p = 0.01). Protective effects were consistent across alternative follow-up durations, grace, and model specifications.

Additional reviews, including those limited to frequent primary care users and time-to-event models, supported the primary findings. No effects on other common diagnoses or preventive health behaviors were observed, indicating that the result was specific to dementia. Comparative RD using an additional ineligible cohort yielded a similar effect size of 1.5 percentage points. Kaplan-Meier diagrams and cumulative incidence curves further demonstrated the delayed onset of dementia in those eligible for vaccination.

The study concluded confusion by confirming that no other interventions used the same date-of-birth eligibility rule and showing that the effect on the 1936 birth threshold was unique. Analyzes that moved the threshold to nearby years did not show a similar effect, further validating the causal interpretation.

It is also important to note that dementia diagnoses are essentially under-considered in the primary care data analyzed. For example, only about 1.4% of patients aged over 65 in the Pens dataset had a diagnosis of dementia, compared to an estimated 8.4% prevalence in the general Australian population. This underdiagnosis means that the observed absolute effect size may not fully reflect the influence of Hz vaccination on dementia risk in the broader population.

These results, combined with similar research from Wales, provide consistent and convincing evidence that HZ vaccination can help prevent or delay the onset of dementia.

Conclusions

In conclusion, this study showed that individuals eligible for free Hz vaccination were significantly less likely to be diagnosed with dementia based on their date of birth over a follow-up period of 7.4 years. The use of a quasi-experimental design enabled comparison between nearly identical groups, minimizing confounding and providing stronger causal inference than traditional observational studies. These findings highlight the potential for HZ vaccination as a cost-effective intervention for the prevention of dementia. However, further studies in additional populations, as well as mechanistic and clinical research, are needed to explore the biological pathways, generalizability, and policy implications of these promising findings.

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