Effect of herpes zoster vaccination on dementia occurrence: A quasi-experimental study in Australia

Importance Taking advantage of a natural experiment in Wales, our group has recently provided evidence that herpes zoster (HZ) vaccination appears to prevent or delay dementia. Exploiting a similar natural experiment in Australia, this present study investigated the effect of HZ vaccination on dementia occurrence in a different population and health system setting. Objective To determine the effect of HZ vaccination on the probability of receiving a new diagnosis of dementia in the future. Design, Setting, and Participants In Australia, starting on November 1 2016, live-attenuated HZ vaccination was provided for free to individuals aged 70 to 79 years of age through primary care providers. Thus, those whose 80 th birthday was just a few weeks prior to November 1 2016 never became eligible, whereas those whose 80 th birthday was just a few weeks later were eligible. The key strength of our approach is that one would not expect that these comparison groups who differ in their age by only a minute degree would, on average, differ in any of their health characteristics and behaviors. We analyzed primary healthcare records with week-of-birth information from 65 general practices across Australia using regression discontinuity. Exposure Eligibility for HZ vaccination based on one’s date of birth. Main outcome New diagnoses of dementia as recorded in primary care electronic health record data. Results As expected, in our sample of 101,219 patients, individuals born just before versus shortly after the date-of-birth eligibility threshold (November 2 1936) for HZ vaccination were well-balanced in their past preventive health services uptake and chronic disease diagnoses. There was an abrupt increase of 16.4 (95% CI: [13.2 – 19.5], p < 0.001) percentage points in the probability of ever receiving HZ vaccination between patients born shortly before versus shortly after the date-of-birth eligibility threshold. The eligibility rules of the HZ vaccination program, thus, created comparison groups just on either side of the date-of-birth eligibility threshold who were likely similar to each other, except for a large difference in their probability of receiving the intervention (HZ vaccination) of interest. Drawing on a sample of 18,402 patients, we find that eligibility for HZ vaccination (i.e., being born shortly after versus shortly before November 2 1936) decreased the probability of receiving a new dementia diagnosis over 7.4 years by 1.8 percentage points (95% CI: [0.4 – 3.3], p = 0.013). Being eligible for HZ vaccination did not affect the probability of taking up other preventive health services (including other vaccinations), nor the probability of being diagnosed with other common chronic conditions than dementia. Conclusions and Relevance Corroborating our quasi-experimental findings from Wales in a different population, this study provides important evidence on the potential benefits of HZ vaccination for dementia because its quasi-experimental design allows for conclusions that are more likely to be causal than those of more commonly conducted associational studies. Key points Question What is the effect of herpes zoster vaccination on the probability of receiving a new diagnosis of dementia in the future? Findings In this quasi-experimental study of electronic health record data from Australia, being eligible for herpes zoster vaccination based solely on one’s date of birth significantly decreased the probability of receiving a new dementia diagnosis over 7.4 years by 1.8 percentage points. Meaning: Due to its quasi-experimental design, this study provides evidence for a beneficial effect of herpes zoster vaccination for preventing or delaying dementia that is more likely to be causal than the associations reported in the existing correlational evidence.