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

Abstract

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.

Fig. 1:

Flowchart of Development of PenCS Patient Sample Abbreviations: HZ = Herpes Zoster; MSE = Mean Squared Error

Fig. 2:

The effect of being eligible for HZ vaccination on new diagnoses of dementia.^1,2 Abbreviations: HZ = Herpes Zoster; CI = Confidence Interval; MSE = Mean Squared Error ¹ Dots show the point estimate and horizontal bars the 95% confidence interval. ² The main specification used triangular kernels, a local linear polynomial, and observations within the MSE-optimal bandwidth.

Fig. 3:

The effect of being eligible for free HZ vaccination on new diagnoses of dementia, across different grace and follow-up periods.^1,2 Abbreviations: HZ = Herpes Zoster; CI = Confidence Interval ¹ With “grace periods” we refer to time periods since November 1 2016 after which follow-up time is considered to begin to allow for the time needed for a full immune response to develop after vaccine administration. ² Horizontal bars depict 95% confidence intervals.

Fig. 4:

Effect of being eligible for HZ vaccination on the 15 most common subsequent clinical diagnoses and uptake of other preventive health services during our 7.4-year follow-up period.^1,2,3 Abbreviations: PPV = Pneumococcal Polysaccharide Vaccine; DPT = Diphtheria, Tetanus, and Pertussis; CI = Confidence Interval ¹ Horizontal bars depict 95% confidence intervals. ² The codes used to define each condition are shown in Table S1. ³ Cancer screening refers to the uptake of colorectal or breast cancer screening. As per Australian cancer screening guidelines, this was defined as uptake of fecal occult blood testing (for colorectal cancer screening) and mammography (for breast cancer screening).^,