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Reviews of "Causal Evidence that Herpes Zoster Vaccination Prevents a Proportion of Dementia Cases"

Reviewers: M Anderson (UC Berkeley) |📗📗📗📗◻️• E Rocca (Oslo Metropolitan University) | 📒📒📒◻️◻️

Published onJun 28, 2023
Reviews of "Causal Evidence that Herpes Zoster Vaccination Prevents a Proportion of Dementia Cases"
key-enterThis Pub is a Review of
Causal evidence that herpes zoster vaccination prevents a proportion of dementia cases
Causal evidence that herpes zoster vaccination prevents a proportion of dementia cases
Description

The root causes of dementia are still largely unclear, and the medical community lacks highly effective preventive and therapeutic pharmaceutical agents for dementia despite large investments into their development. There is growing interest in the question if infectious agents play a role in the development of dementia, with herpesviruses attracting particular attention. To provide causal as opposed to merely correlational evidence on this question, we take advantage of the fact that in Wales eligibility for the herpes zoster vaccine (Zostavax) for shingles prevention was determined based on an individual9s exact date of birth. Those born before September 2 1933 were ineligible and remained ineligible for life, while those born on or after September 2 1933 were eligible to receive the vaccine. By using country-wide data on all vaccinations received, primary and secondary care encounters, death certificates, and patients9 date of birth in weeks, we first show that the percentage of adults who received the vaccine increased from 0.01% among patients who were merely one week too old to be eligible, to 47.2% among those who were just one week younger. Apart from this large difference in the probability of ever receiving the herpes zoster vaccine, there is no plausible reason why those born just one week prior to September 2 1933 should differ systematically from those born one week later. We demonstrate this empirically by showing that there were no systematic differences (e.g., in pre-existing conditions or uptake of other preventive interventions) between adults across the date-of-birth eligibility cutoff, and that there were no other interventions that used the exact same date-of-birth eligibility cutoff as was used for the herpes zoster vaccine program. This unique natural randomization, thus, allows for robust causal, rather than correlational, effect estimation. We first replicate the vaccine9s known effect from clinical trials of reducing the occurrence of shingles. We then show that receiving the herpes zoster vaccine reduced the probability of a new dementia diagnosis over a follow-up period of seven years by 3.5 percentage points (95% CI: 0.6 - 7.1, p=0.019), corresponding to a 19.9% relative reduction in the occurrence of dementia. Besides preventing shingles and dementia, the herpes zoster vaccine had no effects on any other common causes of morbidity and mortality. In exploratory analyses, we find that the protective effects from the vaccine for dementia are far stronger among women than men. Randomized trials are needed to determine the optimal population groups and time interval for administration of the herpes zoster vaccine to prevent or delay dementia, as well as to quantify the magnitude of the causal effect when more precise measures of cognition are used. Our findings strongly suggest an important role of the varicella zoster virus in the etiology of dementia.

To read the original manuscript, click the link above.

Summary of Reviews: This study finds a protective effect of the herpes zoster vaccine Zostavax against dementia through a regression discontinuity design. Reviews considered this study to be potentially informative to reliable, with strong points including its use of a natural experiment and regression discontinuity analysis, as well as its large sample size. However, reviewers suggested further discussion of stratified analyses, vaccine record data, and follow-up period, and identified the statistical significance as lower than ideal.

Reviewer 1 (Michael A…) | 📗📗📗📗◻️

Reviewer 2 (Elena R…) | 📒📒📒 ◻️◻️

RR:C19 Strength of Evidence Scale Key

📕 ◻️◻️◻️◻️ = Misleading

📙📙 ◻️◻️◻️ = Not Informative

📒📒📒 ◻️◻️ = Potentially Informative

📗📗📗📗◻️ = Reliable

📘📘📘📘📘 = Strong

To read the reviews, click the links below.

Comments
3
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Ilsay stone:

abcd

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Charmaine Mia:

The title implies fnaf that the study aimed to establish a direct cause-and-effect relationship between herpes zoster vaccination and dementia prevention.