A natural experiment on the effect of herpes zoster vaccination on dementia, 2025, Eyting et al
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Are you referring to the new study linked in another thread?
It's basically the same methodology as this thread's study, but instead of looking at dementia diagnoses, they looked at two other metrics: diagnosis of mild cognitive impairment and death from dementia. So something like a sensitivity check. If the effect they saw of vaccines reducing dementia is real, then you should also see the vaccine reducing these other dementia related metrics - and they did.
Are these studies demonstrating causality? While it's still not a randomized controlled trial, it's about the closest you could get from observational data. Instead of researchers splitting a group of people into a treatment group and a control group at random, it was basically the government doing that by choosing who was allowed to get the vaccine. Though it wasn't exactly random - they split based on whether people were born before or after a specific date. But they argue that apart from whether or not they were eligible for the vaccine, these two groups did not systematically differ in any other major ways.
Then they looked at the population several years after becoming eligible for the vaccine. The birthdate cutoff was September 2, 1933. People born after could get it (and about half did) and people born before could not. They checked the dementia rates of people born on either side of that birthdate. You would expect a smooth transition in dementia rates, but they saw a sudden decrease in cases for people born right after that date. Figure 3 from this thread's study shows that sudden change:
Though it appears that the effect is really only apparent for women. This is split by sex:
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Peter T
Senior Member (Voting Rights)
I am not sure now as I had not realised there were two separate studies/threads until after I had commented. Brain fog quite foggy today.
With the change in vaccine eligibility, people still had to make an active decision to have it, and there was some confusion on the ground about who was eligible. As a result of the NHS promotion I had asked my GP practice for the jab, but was told I was not eligible, however several months after that my practice invited me to book in for the jab. However I guess given a 50% take up rate it makes selection bias less likely an issue.
That's the thing. Selection bias doesn't really matter here.
Simple way to imagine it: there's a room of people. They all randomly decided to wear a red or blue shirt that morning (akin to being born before or after the cutoff date in the actual study).
Someone walks in and says "people wearing red, you can have the vaccine if you want. People wearing blue are not allowed."
Imagine in the red group, there is some intense selection effect. Only the people who are very unlikely to get dementia anyway end up taking the vaccine for whatever reason. This would be a problem if you were comparing the people who took the vaccine to those that didn't.
But that's not what they did. They compared the entire red group to the entire blue group. There should be just as many people who are likely to naturally get or not get dementia in both groups. So they're not actually "selecting for" healthier people in the red (vaccine) group.
Imagine there was no real effect from the vaccine. If you compare the red group to the blue group, there should be no difference in dementia rates no matter who in the red group actually was able to or decided to take the vaccine. Yet the study found a difference in dementia rates.
Peter T
Senior Member (Voting Rights)
Thank you @forestglip
Utsikt
Senior Member (Voting Rights)
Is that right, though?
They say this about education:
Equal level of education != equal years of education across the date threshold, because the people after the threshold presumably required one more year of education to get the same level of education.
My mom’s equivalent to a BSc took 14 years of school in total. 9+3+2, with 2 being the BSc-equivalent. Mine took 16 years due to changes in the length of the education: 10+3+3. Yet we have the same level of education (if you exclude my MSc from the calculations).
If eligibility for school was the reason for having more or less dementia, then you'd expect to see the same effect in other years, right? Instead of splitting the groups by being born before or after September 2, 1933, what if you split groups by being born before or after September 2, 1932? The same effect due to entering school a year early should still apply.
But they say the drop in dementia cases was not seen when changing the year but otherwise repeating the same analysis:
Sure, maybe something in this specific year changed in regard to education. But as far as I know, the criticism didn't suggest what that might be, so it's just speculating that some unknown thing relating to education happened and that this is more likely than the known major event of being eligible for vaccination.
I think she might have missed that sensitivity check in the paper. Here's someone asking her if the peer reviewed version of the study checking other years allays her concerns (her post was about the preprint).
The same sensitivity check the person asked about was in the preprint too, though.
She wrote an updated critique for the peer-reviewed version which might provide some clarity, but it's behind a Substack paywall. [Edit: Nevermind, I think that's just the preprint criticism copied from Medium to Substack. She said to stay tuned for a post about the peer reviewed version, but I don't know if she ended up writing one.]
Edit: Another person asking about if it would be better if the authors did the thing that they did do:
Response:
The same sensitivity check the person asked about was in the preprint too, though.
She wrote an updated critique for the peer-reviewed version which might provide some clarity, but it's behind a Substack paywall. [Edit: Nevermind, I think that's just the preprint criticism copied from Medium to Substack. She said to stay tuned for a post about the peer reviewed version, but I don't know if she ended up writing one.]
Edit: Another person asking about if it would be better if the authors did the thing that they did do:
Response:
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Posts about different papers have been split off to their own threads:
The recombinant shingles vaccine is associated with lower risk of dementia, 2024, Dercon et al
Lower risk of dementia with AS01-adjuvanted vaccination against shingles and respiratory syncytial virus infections, 2025, Taquet et al
The recombinant shingles vaccine is associated with lower risk of dementia, 2024, Dercon et al
Lower risk of dementia with AS01-adjuvanted vaccination against shingles and respiratory syncytial virus infections, 2025, Taquet et al
The change in risk in females looks quite compelling. It's interesting that there was no change in risk in males.
Scrabbling for an alternative explanation, there is the fact that the people on the 'no vaccination' side were born and may have had their earliest years more affected by the Great Depression and the industrial decline in Wales before it. (The study is on data from Wales. The study looked at people born up to 3 years either side of the Sep 2033 date.
It seems likely that many of the babies in those early 1930s had a tough start to life. I suppose it's conceivable that the girl babies might have been a bit more deprived than the boy babies?
AI says:
I think things were still tough in Wales after 1933. But, perhaps the earlier years were more dislocating and people adapted over time. Scarlet fever most affects children aged 2 to 10 years old, so maybe that scarlet fever epidemic in Wales in 1933 affected the people born before Sep 1933 and that set people up for earlier dementia? Maybe the decline in industries in Wales actually reduced levels of environmental pollution over time, maybe having less coal dust in the home environment or not having a father exposed to the toxins and lack of sun of coal mining was a pre-natal advantage?
I don't think my alternative theories are rock solid, far from it. But, I think there are enough questions there that this study isn't the last word on the idea of the shingles vaccine being protective against dementia. (I haven't looked at the other papers.)
I wonder how the researchers chose that 'three years before - three years after' time frame. Perhaps it was a nice coincidence that the timing gave the most compelling result?
Scrabbling for an alternative explanation, there is the fact that the people on the 'no vaccination' side were born and may have had their earliest years more affected by the Great Depression and the industrial decline in Wales before it. (The study is on data from Wales. The study looked at people born up to 3 years either side of the Sep 2033 date.
Wikipedia said:
It seems likely that many of the babies in those early 1930s had a tough start to life. I suppose it's conceivable that the girl babies might have been a bit more deprived than the boy babies?
AI says:
I think things were still tough in Wales after 1933. But, perhaps the earlier years were more dislocating and people adapted over time. Scarlet fever most affects children aged 2 to 10 years old, so maybe that scarlet fever epidemic in Wales in 1933 affected the people born before Sep 1933 and that set people up for earlier dementia? Maybe the decline in industries in Wales actually reduced levels of environmental pollution over time, maybe having less coal dust in the home environment or not having a father exposed to the toxins and lack of sun of coal mining was a pre-natal advantage?
I don't think my alternative theories are rock solid, far from it. But, I think there are enough questions there that this study isn't the last word on the idea of the shingles vaccine being protective against dementia. (I haven't looked at the other papers.)
I wonder how the researchers chose that 'three years before - three years after' time frame. Perhaps it was a nice coincidence that the timing gave the most compelling result?
Note that the regression they did weighed birthweeks closer to the cutoff point more heavily. That's the grey shading of the dots in the figures above. It looks like past about [edit: two years] on either side, there was very little weight given to the data points. They did this because the further apart people are in time of birth in the two groups, the more confounders you'd expect that could skew the analysis.
Paper said:
The main thing of interest is how suddenly the probability of dementia drops for people born directly after the cutoff. I'd expect it to be more gradual if it was due to something like the Great Depression, which didn't have a hard cutoff.
If there was confounding, which I think is possible, I think it'd be related to education. Starting school a year later is the only relevant event I know of, apart from vaccination, that was a major difference in life events between people born directly on either side of that birthdate cutoff.
Someone's comment on Pubpeer noted a potential interesting detail about the groups being in different school years:
Another thing that ChatGPT suggested to me when I was trying to get it to suggest confounders is related to school year and World War II.
It said that schooling begins at age 5 in Wales, which seems right. So children born in the weeks before September 1933 would have been 5 before September 1, 1938 and would have entered school that year. Children born in the weeks after, would have entered school a year later, at the end of 1939. Notably, World War II started September 1, 1939.
Is there a reason children first starting school immediately at the start of WWII would end up better protected from dementia than children who had already completed a year of school? I'm not sure what the connection would be.
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Kitty
Senior Member (Voting Rights)
It doesn't sound all that convincing, though. Dementias strike highly educated and highly intelligent people as well as ones with little formal education and normal intelligence.
What interests me more is the apparent immune component to dementia susceptibility, and the female bias in protection from vaccination. It almost appears as if there are two types of susceptibility, and/or two routes into developing the disease.
Yes, it's hard to see how one extra year of schooling would make a difference to dementia susceptibility. I'd bet on the impact of the 1933 scarlet fever outbreak over that.
Yes, if it was education-related confounding, I don't think it'd just be something like they learned more in school or had better teachers or something like that. I'd think it'd be something like people existing in a different school year with a whole different group of peers and possibly life events, might have had differences in various major ways from those in a different school year.
Though I still think the vaccination being responsible for the effect is probably most likely, considering that there seem to be a lot of studies finding associations between dementia and vaccines or infections in ways other than this study, with some linked above.
Kitty
Senior Member (Voting Rights)
I think that would need more research anyway, as some primary schools have had staged entrance for decades. My elderly neighbour, for instance, told me a story of having to start school one freezing January because her birthday was in October, which stuck in my mind because my best friend (born in September) started after Christmas too. The neighbour's age suggests that would have been in the late 1940s, and for my friend it was the mid-60s. England, though, not Wales.