Causal evidence that herpes zoster vaccination prevents a proportion of dementia cases, 2023, Markus Eyting

Abstract
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 individual's 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 patients' 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 vaccine's 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.

https://www.medrxiv.org/content/10.1101/2023.05.23.23290253v1

 

Wow. The effect isn’t as persuasive as the recent paper showing a causal association between EBV and MS but still.

 

Dementia arises from a number of different conditions and causes not all of which are irreversible and some of which are better understood than others. Presumably it would be helpful to know if the 20% reduction related to any specific form of dementia.

The article says:

which I did not expect. A significant number of patients had a diagnosis of both Alzheimer’s and vascular dementia. However I remain concerned about how accurate/reliable electronic medical records are.

[Edited to add first quote to add final two sentences]

 

My mother developed dementia soon after she developed shingles in her mid 70s. She was never vaccinated. The shingles went away on it's own after 6 weeks but she told me about an experience she had where she felt like a lightening bolt went through her head one day. I didn't know what make of it b/c she didn't talk much about her health, she was healthy all her life.

She was diagnosed by one doctor as having vascular dementia, the CT scan image showed that she had multiple broken blood vessels in her brain, a few months later she could no longer talk. Another doctor dx her with Alzeimers.

 

Does shingles vaccination cut dementia risk? Large study hints at a link

"Vaccination against shingles might also prevent dementia, such as that caused by Alzheimer’s disease, according to a study of health records from around 300,000 people in Wales. The analysis found that getting the vaccine lowers the risk of dementia by 20%. But some puzzling aspects of the analysis have stirred debate about the work’s robustness.

The study was published on the medRxiv preprint server on 25 May and has not yet been peer reviewed.

“If it is true, it’s huge,” says Alberto Ascherio, an epidemiologist at Harvard University in Cambridge, Massachusetts, who was not involved in the study. “Even a modest reduction in risk is a tremendous impact.”"

https://www.nature.com/articles/d41586-023-01824-1

 

Merged thread

GWAS - shingles vaccine

Interesting - made me recall that GWAS identified immune related genes in dementia. These researchers are suggesting that a shingles vaccine may reduce cases.
Twitter/X post by Pascal Geldsetzer & link to accessible (Guardian) article* * pre-print
https://twitter.com/user/status/1661776663074738176



*https://www.theguardian.com/society/2023/feb/19/could-alzheimers-be-caused-by-an-infection
**https://www.medrxiv.org/content/10.1101/2023.05.23.23290253v1

 

Mij your description reminds me of a famous mountaineer [Hamish Macinnes] who developed dementia following an infection - he recovered but had to recreate his memories.

@Peter Trewhitt no biomarkers for "different" types of dementia so one possible explanation is that the current classification doesn't separate pathology?

 

Radom thought - if the dementia population had a common pathology then you'd think GWAS would clearly pick that up. The APOE [Alzheimer] gene was identified relatively early on (via GWAS) but it took a number of large GWAS studies (combined data) before two further [clearly immune related] genes were identified. So if this study holds up then 20% common pathology still requires large GWAS?