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Evidence that the shingles vaccine prevents a good chunk of dementia cases (twitter.com/pgeldsetzer1)
667 points by guiambros 13 days ago | hide | past | favorite | 273 comments





Shingles (Herpes zoster) is implicated. The whole 'lifelong nervous system infection' does seem a bit awful. I bet if we chip away at new kinds of herpes viruses, we'll find a fairly drastic reduction in Alzheimers.

"There is mounting evidence that herpes [simplex] leads to Alzheimers", so, HSV1/2 also.

And apparently having APOE4 genome makes it all worse. HSV1+APOE4=12x risk.

https://www.bbc.com/future/article/20181022-there-is-mountin...

EDIT: for clarity, the twitter thread showed that the shingles vaccine drastically reduces risk


Does this mean the chickenpox vax will eliminate Alzheimer's? How many years til we know?

Chicken pox doesn't impact HSV1/2 which a lot of people have and is also implicated in this analysis. There is, however, a doctor working on a cure and vaccine for HSV1/2 that will hopefully be available within the decade.

Unfortunately, there are several others that can be asymptomatic.

"Nine herpesvirus types are known to primarily infect humans... More than 90% of adults have been infected with at least one of these, and a latent form of the virus remains in almost all humans who have been infected."

https://en.wikipedia.org/wiki/Herpesviridae


a doctor working on a cure and vaccine for HSV1/2

Can you share more information on this? Who is this doctor you're referring to?


No idea about the doctor, but Biontech is starting clinical trials [1], and there are a host of other vaccine candidates. Some Russians claim they developed a cure as well [2].

[1] https://investors.biontech.de/news-releases/news-release-det...

[2] https://en.wikipedia.org/wiki/Herpes_simplex_research#Vaccin...


There's a sub reddit I discovered tracking HSV vaccine progress (HSV cure research)

Unfortunately the most promising doctor that was working on a vaccine was only able to show efficacy of 50% in mice. A recent study also showed HSV likely infects more than just cells near the brain. Potentially immune cells too.

Gsk is working on one. Would be interesting to see the results soon. This is a tough nut to crack and clearly not enough money being funneled by governments, as another person mentioned we have almost 3x the amount we spent on covid for a new war.


Somewhere on the internet is a website that is keeping track of everyone working on HSV-1 and HSV-2 treatments, but I’m not able to find it just now. There are several entities working on HSV-1 and HSV-2 vaccines.

MMR-V was first approved in 2005 in the US. Alzheimer’s-type dementia usually has onset in the mid-60s and 70s.

However, there are other dementias (i.e. vascular) that have other etiologies.


Nitpicky, but the chicken pox vaccine came out in 1995 (not combined with MMR). So that’s 10 fewer years to wait :)

1995 for USA. ‘84 for Germany and Sweden:

https://apps.who.int/iris/bitstream/handle/10665/242227/WER8...


So we should start seeing early results in the next decade?

Introduced in 1995 in US, but usage increased over a decade - see first graph: https://xkcd.com/1950/

Vaccine approvals in years that end in Roman numeral V‽ That’s hardly a coincidence! /s

It's very very unlikely that chickenpox vax will eliminate Alzheimer's, both in terms of chickenpox vaccine effectiveness, as well as there are almost certainly non-VZV "causes" for Alzhiemer's.

But yes, it's quite likely that widespread chickenpox vaccine will help reduce Alzheimer's rates.

It'd probably be a few more decades before you'd expect the cohort that received childhood chickenpox vaccines to reach an age where we'd see siginficant rates of Alzheimer's. Even then, it would it'd probably be quite difficult to disentangle.


The vaccine likely won't eliminate the virus or the existing impacts of the virus.

Their idea in mentioning the chickenpox vaccine is that if the shingles vaccine is effective against dementia in this way, then you'd expect an even greater effect from kids generally having gotten the chickenpox vaccine and therefore not getting infected with the varicella zoster virus in the first place.

I think that Alzheimer's likely has many causes.

This research indicates that the chickenpox/shingles virus may be related to about 20% of dementia cases - so not all Alzheimer's but an appreciable amount.

It could be that other cases are caused by other Herpes viruses, or maybe Epstein Barr - vaccines for those may reduce it even more


It was my understanding that shingles and chickenpox vaccination are positively correlated

If you mean the vaccine leads to shingles in those who receive it, I don't think there is evidence for that. When I had shingles in my early 40s, my doctor did mention that she is seeing it occur earlier in adults who never received the vaccine. The working theory was that we don't come in contact with the virus nearly as much as we used to and our immune systems can't suppress it as easily when it flares up. I don't know if that's actually been studied though.

This raises a question that probably hasn't been answered yet: does the shingles vaccine prevent Alzheimers?

(Edit: sorry, I read the comments before reading the link)


"We estimate that over a 7-year follow-up period, getting vaccinated averts one in five new dementia diagnoses."

> does the shingles vaccine prevent Alzheimers?

That’s what the pre-print addressed.


The anti vax screw will probably wonder if injecting the vaccine actually increases your odds of Alzheimers since you're getting a partial version of the virus when doing so.

The data from this study is pretty definitive that it decreases your odds, not increases them.

Not really. They used the cutoff date to develop a theory. That is, those before the date couldn't get the vax vs those after the date that did.

So far, so good.

However, not everyone after the date got the vax. That is, like tge before date "control" there are a post-date group who also did not get the vax. Oddly, there's no mention how this group fared.

Obviously, they know this group exist. And that the initial theory would be ideal to apply to this group. That didn't happen.

That would be definite. As it is, a key and obvious piece is missing.


That won't stop 'em. Confidently-asserted lies are more compelling, it seems.

It would be ideal to wait for the people you hate to express the ideas you hate before hating them.

I never stated which one I was.

That's worse. Unprompted mocking was the best interpretation of your post.

And Facebook will be more than happy to promote and spread that lie. Imagine all the “engagement” they’ll get out of it.

I’ll never blame Facebook, as so many others do, when it’s people themselves that lie and want to believe the lies.

It's one thing for people to lie and/or believe lies, it's another thing for someone to profit off those lies and steer people towards them on a medium that claims to be a communications platform to keep in touch with friends & family.

Seems the chickenpox vaccine actually does indirectly increase your chances of getting Alzheimer’s: https://pubmed.ncbi.nlm.nih.gov/18999945/

“ With childhood varicella vaccination in the United States have come concerns that the incidence of herpes zoster may increase, because of diminishing natural exposure to varicella and consequent reactivation of latent varicella zoster virus.”

“As the rates of VRHDs and the associated charges have decreased, there has been a significant increase in HZHDs and associated charges, disproportionately among older adults.”


The chickenpox vaccine absolutely decreases the chances of the people getting the vaccine of getting dementia. This has a side-effect of decreasing the exposure of older adults to new chickenpox infections, which increases their odds of developing shingles.[1]

But as long as those older adults are getting the shingle vaccine, their odds of getting dementia should reduce as well.

[1] - Intermittent infection with chickenpox boosts the adaptive immune response to the chronic chickenpox infection that most people who ever caught the disease have. This intermittent boosting helps prevent flareups of the chronic chickenpox infection (also known as shingles), which is likely the causative factor in chickenpox-related dementia. Alternatively, instead of getting intermittently infected with chickenpox, they could just get a shingles vaccine instead to boost their immune response against their previously acquired chronic infection.

I presume that this intermittent exposure to chickenpox is greatest in adults with children (and grandchildren). Possibly explaining the decrease in dementia for older people with adult children: https://www.sciencedirect.com/science/article/pii/S235282732...

> Having 3+ children, adult daughter(s), or biological children was associated with lower risk of cognitive impairment.


> The chickenpox vaccine absolutely decreases the chances of the people getting the vaccine of getting dementia.

I'm a bit too certain with this phrasing. This should be theoretically the case given that vaccination decreases the odds of getting a chronic herpes zoster infection.


Does it lower it compared to not getting the virus nor the vaccine?

Seat belts lower car accident deaths. But not lower than simply not driving. Isn't this a similar example?


Never getting the virus is always better. The chickenpox vaccine helps prevent chronic viral infection.

Assuming you're asking about whether shingles vaccination is comparable to re-exposure.

For the youth a vaccine should absolutely reduce the risk better than having a chronic infection to actively fight against when it flares up.

For non-chickenpox-vaccinated adults, I have no clue. I would expect shingles vaccination would be comparable as it effectively does the same thing. But there might be an added response from other parts of the adaptive immune response against a viral invader.

Regardless, with respect to the chickenpox vaccine, I think it's better to take a risk on the current middle-aged folks and elderly in favor of basically eliminating all of the risk for the young and future generations. Since this risk increase would be primarily for middle-aged folks and elderly who have children and grandchildren (as childless adults are already at increased risk from fewer re-exposure routes), I think it makes moral sense that they preference the health of their descendants over themselves.


Yes, not getting viruses at all is preferable to getting vaccines. If you figure out how to make that one work let me know.

Make 90%+ of your neighbors get vaccinated, then bask in your glorious herd immunity.

That's not enough, since people travel or occasionally go places where large groups are present (church, concerts etc.)

The vaccine may indirectly increase the risk that people who did not receive the vaccine get shingles. As far as we know, people who got the chickenpox generally don’t get shingles.

Similarly, there is now extemely strong evidence that the Epstein-Barr is causal in multiple sclerosis. The vast majority of people are infected with EB, with most never having symptoms. However, a nonsignificant minority aren't. A large-scale study of data covering 10 million US military service people found that those infected with EB were 32 times more likely to develop MS.

Epstein-Barr has long been thought to be a culprit in everything from MS to dementia to especially CFS. But that's a real problem: there are no antivirals developed that are particularly effective against it. EBV research has been a backwater in medicine.

> EBV research has been a backwater in medicine

Truth. I moderate a forum for people suffering from Mononucleosis and the overwhelming feeling is abandonment and fear. Granted there's some inverse survivorship bias -- people who feel well supported and educated by the medical system usually don't post in support groups -- but it's so hard seeing so many people suffering for so long (SO LONG -- years of fatigue and malaise, in many cases) for something that has basically no first-line therapy.


Academic disciplines and medical research being famously kind to disabled people entering them too, right?

With most of these patients living decades after diagnosis, you would imagine that a reasonable chunk of them would give the rest of their life to researching a cure for their disease.

Yet, while it seems common to do charity awareness fundraisers at marathons, it does not seem common for people to go learn biochemistry and work on solving the problem directly.

Compare that to tech, where a huge chunk of the people here have probably written a computer program to solve some itch of theirs. Saying "I'm doing a charity fundraiser to fix the print preview bug in libreoffice" would be crazy.

I wonder if perhaps these people all have so little useful productivity left that it isn't even worth starting to learn biochemistry?


Abandoning one’s livelihood to spend years in poverty studying advanced science at university in the distant hope that in a few decades you might contribute to a cure is a little different from taking a few weekends, or even a few months of weekends, to scratch a programming itch.

Also it's absurdly difficult to be an academic with a chronic disability, speaking as someone with a chronic disability (MS) who was diagnosed in grad school and who left the sector because of it.

Moving multiple times, as is usually necessary during the post-doc years, means moving away from your support system and interrupting your continuity of medical care. Your activities of daily living require more time: You can't spend 12+ hours a day in a lab if you need to sleep for 12 hours a day. You aren't usually paid enough to pay for all the little extras that make life easier as a disabled person: No delivery services, no supplements, no helpful but extra costing medical services like massages/PT/etc. And stress usually worsens your prognosis: Academia's reliance on competition and stressing out post-docs combined with stress being associated with relapses was one thing that made me nope out. I'm not risking my ability to walk for your institution's prestige.


I have MS and am in grad school. It is very hard.

I was 'lucky' in that I had my first relapse in the last semester of my Master's program, so I could limp along and finish the degree and decide not to pursue a PhD. An academic career was right out, especially as a first-generation student.

I decided to go to gradschool after the big relapse took me down. I’m going to do this in spite of MS. Fuck MS. My MS has hit me in both eyes and ruined my old career (I was a pilot).

Anyway, I’m going to push myself to build new neurons faster than it bashes the old ones. I’m learning Spanish, do some programming for school every day, and walk a lot. It helps - even if my vision is pretty bad I feel it really helps.

I did 2 years of Tysabri and then switched to Lemtrada in January. One more dose of that and then theoretically I’m done. Going backpacking this summer in Spain as a big “fuck you” to MS. I’m slowed down quite a bit but not beaten. I will get better or die trying.

It is very hard though, things take longer to do - it’s like I have ADD now or something? I have constructed some compensatory strategies, but yeah… it is hard. Hard to explain but it’s definitely a real thing and especially if I don’t get enough sleep.

My old career is over (hard to fly if you can’t see well), the new one is going to be software engineering/ AI stuff in spite of this shit.

Whatever you do don’t give up. MS is a cruel bitch, but I plan on outlasting this asshole. We’re not far from a real restorative cure.


> It is very hard though, things take longer to do - it’s like I have ADD now or something? I have constructed some compensatory strategies, but yeah… it is hard. Hard to explain but it’s definitely a real thing and especially if I don’t get enough sleep.

Oh my God, the hit to executive functioning is real. And I had zero compensatory structures in place: I specialized in Linguistics and spent most of my high school + undergrad years in language classes, which meant I had an insane memory and was used to relying on it. Also the emotional lability sucks: I cry and laugh in odd situations now and it's so detrimental to being taken seriously.

I'm sorry to hear about your sight: Given how much you relied on it, that has to be a loss. (My vision always sucked - I had eye surgery when I was 3 - so I actually had a bought of optic neuritis and didn't know because 'eh my eyes are always fucked up').

I absolutely agree we can't let MS control our lives. My purpose for downshifting is because the diagnosis shook my worldview enough for me to consider what I actually valued and therefore center it. In my case, I'm a librarian/archivist who's likely to be one of the last people living with a memory of the beginning Web + some of its predecessors (I'm female and from a family with multiple supercentenarians - I have a fair shot at making it to the Web's 100th anniversary) and I think that the training and first-hand knowledge to sort through and add context to what we have from those eras (especially pre IA and Google) is going to be very important but also that interest isn't going to really pick up for another ~30-40 years, so my third responsibility is to live a life that maximizes my odds of living and functioning into my 80s+. First is my own wellbeing and second being that of my family/people.

My diagnosis also completely shattered my worldview and I've had to rebuild my values and morals from the ground up and it turns out that a lot of the goals I used to have are odious to me now.

> on outlasting this asshole

Spite = best motivator.


> Oh my God, the hit to executive functioning is real. And I had zero compensatory structures in place: I specialized in Linguistics and spent most of my high school + undergrad years in language classes, which meant I had an insane memory and was used to relying on it. Also the emotional lability sucks: I cry and laugh in odd situations now and it's so detrimental to being taken seriously.

I don’t quite have the emotional regulatory weirdness but my ability to deal with bullshit, pettiness, or any of that minor sort of tyranny cruel people try to impose is basically non-existent now? I don’t know if that’s the result of immense emotional, spiritual, and personal growth, or if MS clipped the wire that allowed me to ignore bullies? I don’t know but I’m definitely a lot more radical now. What’s weird is I cry a lot more now, and I never used to before, really? It’s ok, it’s good to cry - but I had some toxic masculinity perhaps that MS beat out of me lol.

Also, do you use Anki? I have found that actively practicing with Anki and one of those stupid brain games apps has really helped me build back some of my memory skills. The one thing I routinely forget now is people’s names? But I figure I’d rather have 1000 Spanish words than remember the name of the mailman like I used to. My apologies to, Randy was it? It’s weird, I can remember just fine to write code, I can still do math - the main impediment in school has just been visual… but why the hell can’t I remember names anymore lol? Maybe I just can’t be bothered to give a damn except about people who are important to me?

> I'm sorry to hear about your sight: Given how much you relied on it, that has to be a loss. (My vision always sucked - I had eye surgery when I was 3 - so I actually had a bought of optic neuritis and didn't know because 'eh my eyes are always fucked up').

Man, mine were great. The first time ON just wiped out one eye, but they couldn’t figure out what happened or if it was MS… well they figured it out 4 years later when it took out the other one. I had even gotten a waiver and was back to flying with one eye for a few years. I was fully blind for a bit after the second relapse. Was pretty terrible, but way better than some poor folks. I at least can still move etc. and my eyes have been improving for a couple years, albeit slowly, but now, while I cannot drive (let alone fly) I’ve got enough vision to go back to school.

> I absolutely agree we can't let MS control our lives. My purpose for downshifting is because the diagnosis shook my worldview enough for me to consider what I actually valued and therefore center it.

Dude are you my girl twin? This is basically why I went back to school. Losing my job wiped out a massive part of my identity - I’d been a professional pilot since I was 19 and had literally not seen any other thing that I wanted to do. Basically I had to completely reinvent and recreate who I was through all this. Anyway, the big epiphany for me was major changes in how I view the world - particularly with regards to what is important and where I fit into it. I am not going to go down without a fight even if my only purpose is to serve as an example to others.

I was a workaholic. I still like to work but my motivations and the reasons I go are much different now. My wife makes enough to support our family now, albeit not as comfortably as before, but good enough. When I finish grad school the money I make from whatever I do will be able to be spent on fun, experiences with the kids, and helping in our community - that’s a massive change from where we were before, basically just focused survival or getting more money for money’s sake and toys.

Getting sick was like crossing an event horizon for me in terms of personality. I remember who/what I was, but there is no going back and I couldn’t see myself today back then. I am fully a different person now. The essence may be the same, but I am irrevocably changed. That’s ok - I wouldn’t trade my life for someone else’s, but man, MS is a bastard.

We got this shit.


> It’s ok, it’s good to cry - but I had some toxic masculinity perhaps that MS beat out of me lol.

I don't even have the 'toxic masculinity' excuse since I'm a girl, but I was also emotionally constipated. It definitely takes some getting used to.

Anki is great - spaced repetition was my best friend in school since I focused on languages/linguistics. Unfortunately my main memory issue seems to be remembering conversations I've had and forgetting/transposing random words. My memory is still objectively good, but it used to be amazing so it chafes. I know you understand since your vision was like that.

> Dude are you my girl twin? This is basically why I went back to school. Losing my job wiped out a massive part of my identity - I’d been a professional pilot since I was 19 and had literally not seen any other thing that I wanted to do. Basically I had to completely reinvent and recreate who I was through all this. Anyway, the big epiphany for me was major changes in how I view the world - particularly with regards to what is important and where I fit into it. I am not going to go down without a fight even if my only purpose is to serve as an example to others.

I might be! I was also very career focused - I had people pushing me towards academia and assuming I was going to be a professor since I was six years old. My entire sense of self was tied up in my intellectual and productive capacity. I am much angrier and, like you, much less tolerant of injustices now. Shamefully, a large portion of that is because I have experienced a life altering event through no fault of my own and I have more sympathy for others now. It's also made me more aware of the advantages I have and absolutely furious when people who don't have them are taken advantage of.

> My wife makes enough to support our family now, albeit not as comfortably as before, but good enough. When I finish grad school the money I make from whatever I do will be able to be spent on fun, experiences with the kids, and helping in our community - that’s a massive change from where we were before, basically just focused survival or getting more money for money’s sake and toys.

I'm the sole breadwinner for both myself and my sister who is bipolar and can't hold down a job. We have no other help. We're drowning; I hate it here. It's to the point where I'm contemplating trying again to make myself like/tolerate men sexually because God, a spouse or second income would make things so much easier and there is no female dating pool here. Then again, men don't stay with crippled women so that's probably not a great idea either.

I do spend a lot of my free time and mental energy on local matters.

> I am fully a different person now. The essence may be the same, but I am irrevocably changed.

I 100% am different. I view my former self with horror, honestly. I was an arrogant, nasty little shithead. It's a lot easier to speak up now, though. Oh no, you don't like what I say and you might not hire me or say mean things? I wake up every day not sure if I'll be able to walk, anything else seems like small potatoes in comparison.


Indeed, the path to a research career — necessary for the grants and facilities you’ll need to test your hypotheses — involves such high barriers that you would almost need to already be on that path by your freshman year in undergrad.

I was on the biochem track in undergrad. I was particularly interested in disease metabolics and cloning.

I switched to tech and entrepreneurship because it scratched more itches, provided substantially more money, didn't come with the stresses of academia, and could conceivably put me on a path to returning to biochem with loads of resources and full research independence.

I see biochem companies getting venture funding now, but that wasn't always the case. And they're still unfavorable relative to tech ventures.

I still don't think the grad school + academia path is comfortable enough for those that take it. It's a real labor of love, and I admire those that stick with it.


Plenty of alternatives to academia, but then you're working on a company's projects. And yeah, the cost of equipment, not to mention consumables, is prohibitive.

GP does have something right, though. Throwing more money at a problem does not always yield a faster or improved solution. This is well-known in software, but maybe not in other fields.

Money needs to go to educating and recruiting more people to the field. It is not as accessible as programming, and so is harder, but the same concept applies.


"Money needs to go to employing more people in the field."

Provide the employment (at decent wages) and the people will get the training. Provide the education and recruitment without the decent employment and you'll have a lot of ex-job people in other jobs.


> Throwing more money at a problem does not always yield a faster or improved solution.

This cliché probably holds if you are increasing the funding of a single group - doubling Firefox’s income would not improve Firefox.

If you are funding independent groups, chasing different paths and solutions, then more money likely helps. Kind of like VC funding.

Of course having independent groups all chasing a single solution is also a single point-of-failure problem - the dominant amyloid hypothesis of Alzheimer's springs to mind as an example of a lack of diversity.


I can't think of many people who've learned to program to fix a bug that's bothering them. and learning to program in your free time is much easier than switching careers, getting a PhD and securing funding for your lab.

nevertheless, I know a number of people with my genetic disorder (Ehlers-Danlos syndrome) who have become researchers, doctors and PTs because of it. but that's a genetic disorder, so it hits you early enough in life to sway your choice of major.

also, while I get what you're saying about having "little useful productivity left," it comes across as a bit insensitive.


We don't gatekeep tech. Literally anyone can create a PR and submit it to an open repo for consideration.

You can't do the same for biotech. You need a PhD, a reputation, a ton of funding, a bunch of papers, to be even considered for "this person has a clue about this medical issue and might have an answer".

Listening to maintainers talk about their experiences dealing with random weird PRs from random weird submitters, I'm not sure we're doing it right by not gatekeeping it more ;)


It’s not gatekeeping, it’s being able to contribute by having foundational knowledge.

Anyone can (and people often do) make big contributions in health, but it’s hard without deep knowledge.

Not everyone who does software engineering needs a computer science degree.

Meanwhile if I head out to the pub on the weekend I hear people post cancer diagnosis waxing lyrical about how they’re beating their breast cancer with surgery+chemo/radiotherapy with a diet high in antioxidants, ignorant of the fact that one of the ways radiotherapy and chemotherapy works is by sctually causing oxidative damage, so they’re working against it. One of the many ways that doing your own research is counterproductive


To contribute to fundamentally new knowledge in software or CS also can require quite a lot of background learning though. I think the bigger culprit is that biomedical studies are fucking expensive. There needs to be a big upfront commitment, so there is naturally going to be more reliance on credentialism/gatekeeping. If 99% of random self-driven software projects turn out useless to the rest of the world, that's no big deal, and then we just hear about the 1%. But it's not possible in biology.

The time required to test/verify any “answer” in medicine is years or decades and not seconds/hours/days like in software development.

And well experimenting without being almost entirely sure of what you’re doing (and even then sometimes) might have very terrible outcomes.


Principally barrier to entry in the field due to high costs, low iteration rate, required space, safety of operation, and poor information sharing practices in the field.

That's what I would guess. Because otherwise, there's the concerned uncle effect: unaffected agent who has close to maximal aligned incentive.


Programming is much, much easier to learn to a professional level than biochemistry, and open source is much, much cheaper and easier to enter and navigate than medical academia/pharma industry, and adding a software feature is (generally) much easier than discovering or developing a drug.

I think it’s a valid question but expectations have to be tempered by the question of how many people have the means to follow through. Not many are in a position to go (back) to school for a doctorate just to start working on the problem 5-10 years later.


Someone suffering a debilitating illness (often later in life) is probably only slightly more likely to be able to contribute useful research here than someone actually already dead.

What with them suffering the debilitating illness and all, and being well past the age where it would be natural to do a major life change like become a medical research.

You might as well be wondering why Ukraine isn’t encouraging pregnant women to go to the front. I mean, what else do they have to do?


Given the high requirements to enter the field, and a likely mismatch of interests between many of the patients and the interests required, it would probably be more effective to try to fund some researcher directly. Identify someone doing high-quality research in an adjacent area and offer a direct grant of $50k or something to research towards a cure.

Getting access to the resources required for infectious disease research without qualifications is difficult.

>there are no antivirals developed that are particularly effective against it.

What happened to the research into DRACOs? A few years ago I kept hearing about them, but they seemed to vanish.


Is there any evidence of this? I have seen the data but it seems also likely that the same immune issues that cause ms could cause a lapse of resistance to eb.

Antivirals probably won’t help as most infections are silent, a vaccine is needed. Moderna is working on one.

For anyone else reading, EBV is the virus behind mononucleosis.

ahhhh I'm in danger.

We all are.

exists nervously

Can confirm, I have MS and I got EBV about a decade before MS took me down…. It’s crazy what a tiny little virus can do.

EBV reactivation also plays a major role in ME/CFS, a condition that can affect people almost as severely as MS, but at any age. HHV-6 and 7 infections have also been implicated.

The paper mjhay refers to: https://doi.org/10.1126/science.abj8222

EB vs non-EB history also seems to imply distinct but similar conditions.

The evidence implicating EBV in MS is not nearly as strong as this causal evidence.

It's incredibly strong evidence that it's a required but not sufficient condition. I've seen professionals have serious suspicions that the single EBV-negative MS case from the study [1] OP mentioned was a false negative, but apparently it's not easy to confirm.

A single EBV-negative MS case. While there were 955 MS cases that developed in the 0.5M that were EBV-negative at the start of military service. You'd expect there to be about 50. That's pretty compelling evidence.

[1] https://www.usmedicine.com/clinical-topics/multiple-sclerosi...


How about HSV-1/2? Combined this virus is present in about 2/3 people in the US, and resides dormant near the brain (with cold sores).

I thought there's already a strong link with HSV and Dementia, is there any more research looking at this virus and a vaccine?


Yes Ruth Itzaki has been talking about this for years. https://www.beingpatient.com/ruth-itzhaki-alzheimers-viruses...

Potential Rosalind Franklin scenario.

https://www.healthspan.dev is making a mRNA vaccine. Sam Altman funded company.


Not going to be surprised if the most common viruses are what leads to cancer and mRNA is what becomes a cancer preventative as protocols ramp against said viruses.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1994798/

> An estimated 15 percent of all human cancers worldwide may be attributed to viruses, representing a significant portion of the global cancer burden. Both DNA and RNA viruses have been shown to be capable of causing cancer in humans. Epstein-Barr virus, human papilloma virus, hepatitis B virus, and human herpes virus-8 are the four DNA viruses that are capable of causing the development of human cancers. Human T lymphotrophic virus type 1 and hepatitis C viruses are the two RNA viruses that contribute to human cancers.

https://pubmed.ncbi.nlm.nih.gov/25083895/

Kudos to anyone accelerating mRNA in this space.


But why mRNA specifically instead of a protein or other vaccine? What’s the advantage?

mrna vaccines are a lot harder for viruses to mutate away from (and easier to adapt if they do) because they let you target a gene sequence directly.

That doesn't really make sense. Target specifically, and it only takes a minor mutation to escape.

A less-specific vaccine would create immunity against multiple targets, and would logically require more simultaneous mutations to create an escape variant.

Unless your goal is to sell a new vaccine every year (chase your own escape variants, immunity-as-a-service), then MRNA isn't obviously a win.


> Target specifically, and it only takes a minor mutation to escape.

1) Not all sections of a virus mutate at the same rate. Some sections of a virus are highly conserved or the virus simply dies. In Covid-19, for example, the spike protein seems to be difficult to change significantly as it provides the primary entry for the virus into cells.

2) mRNA vaccines tell your immune system "target this specific sequence" and can avoid problematic sequences.

Normally, you have no idea what section of the virus your immune system locked onto. Even worse, if your immune system grabs onto something common (EBV pieces causing MS or alpha-gal from a tick bite, for example), it can hose you bad.


Covid-19 is actually a great example. The spike protein was highly conserved until it became advantageous for it mutate to evade the highly-specific immunity created by mRNA vaccines. Then we got Omicron.

For which the original vaccines are still reasonably effective at keeping you out of the hospital (systemic immunity response).

I am awaiting the trials on the ones that actually provoke immunity in the respiratory mucosa. It would be very nice to not get Covid at all.


Not an expert, but couldn’t the mRNA vaccine target only part of the virus genome that’s stable across mutations/variants? That would give you a broad vaccine resistant to mutations

Stable across mutations? On what timeframe.. Its been stable so far.

However, create a population with narrow immunity based on a single protein, and you create a selection pressure that incentivizes mutations in that protein. Once a successful mutation exists, it has a wide open field to spread unchecked. With broad immunity (multiple proteins) it is much less likely that a variant can realize the multiple simultaneous mutations that would be required to spread effectively.


The one example of mRNA vaccines that we have has resulted in the viruses by and large mutating away from them and they haven't been adapted quickly.

virus mutation rate is proportional to number of infected people, so pandemics will naturally mutate faster. also, the vaccines have been adapted quickly. the pfizer bivalent booster came out 18 months after the regular covid vaccine (9 months after omnicron started circulating) and had extra omnicron protection. that's really fast for drug development (and approximately all of that time was the clinical trial. it's not hard to imagine in a decade or two, that we'll be able to speed up the approval time further as the manufacturers and regulators have more experience with mrna vaccines).

Not sure if this is the case for parent, but there was such a huge marketing push behind the covid vaccines that it's the first thing that jumps to everyone's mind in any vaccine related topic.

It's kind of like after everyone being inundated with talk about covid for years, there is a tendency to assume every health issue is related to it. Some things definitely will be, but it turns out the universe of things that can go wrong with a human body goes far beyond one recent virus.


It's not marketing, mRNA technology is truly a shift in how rapid vaccine development can occur [1] [2].

[1] https://www.jci.org/articles/view/153721

[2] https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8905605/


It's not either/or, both things can be true. The mrna vaccines have probably had more resources spent on promoting them than any product in recent history (ie marketing). I would argue that their mindshare is due to that and not some innate ability of the public to know what will be a successful pharmaceutical technology or not.

This is all orthogonal to whether or not the tech eventually delivers on all the possibilities.


I'm half-assedly pulling this out of recollection. I believe nucleic-acid based vaccines prompt a greater response from the part of the adaptive immune system that is not the antibody part, while protein-based vaccines preferentially boost the antibody response. They do this because the antigen is expressed within the cell.

do you know if this vaccine will work for existing dormant infections?

there’s quite a bit of active HSV1/2 work being done although it’s very early stage. a few vaccines. a cure attempt. unfortunately this virus is not seen as a target for funding. some of the labs working on these are just sub-teams of larger companies working to fight other medical challenges such as HIV or cancer. those get the funding and they are able to set side some money for HSV research.

probably because it’s thought of as a simple skin virus when more likely it’s a nervous system virus that manifests most visibly in the skin


Even if there were a strong link between HSV and Dementia, I don't believe our governments would fast track or fund such research because their priorities.

It would be nice if Gates or Elon Musk would bring the worlds attention to these issues and if something positive comes out of it would be a massive net positive to humanity.


priorities are pretty clear. we spent <$20B on the covid vaccine, operation warp speed. ukraine received $75B in the last year from the u. s. if it was the same price, we could have solved 4 highly infectious diseases in just the last year. i’m not trying to get political on that specific war; just military in general is where the money goes

Imagine if, after the first oil crisis, the US had earmarked 10% of the military’s middle east budget to R&D for energy independence.

We would have solved the global warming problem by the mid 1990’s.


A sufficient number of nuclear power plants would have cost a lot less than that.

You can't (well, couldn't) make steel or concrete from electricity from a nuclear power plant. And up until recently you couldn't really drive a car from the electricity from a nuclear power plant. You can't plow or plant a field, or pave a road, or so many other things.

I think if you look at a breakdown in sources of CO2 emissions, it's less than half. Yes, that's a lot, but it's not the whole story.

I'm 100% for getting off fossil fuels. I drive electric. But the transition is a hell of a lot more complex than "build a lot of nuclear power plants."


I didn't expect it to complete replace all fossil fuel -- just almost all the coal + a large share of the oil. Cars would still have used petrol. Heating could have become largely electric. If they really wanted, they could have used synthetic petrol -- but that is rather inefficient.

The US produced (and produces) lots of oil. It would probably have been enough (or close enough) to make the US entirely independent of OPEC oil.

The two proposed solutions were: military (the road taken), very expensive research (not really taken). I added a third one (nuclear) because it was cheaper and it wouldn't have needed much research. It was a known solution that would have gotten the US most (likely all) of the way towards energy independence and it would have reduced CO2 emissions a lot.


Note that those $20B were not for research but for production and rollout. The research costs (for BioNTech) were in the order of only $1B or two. Source (in German): https://archive.is/L5oFm

Though, obviously, no research lives in a vacuum. Companies profit from universities and the larger educational system, from other researchers laying the groundwork over the years etc.


Well, the US spends far more on elder care than on the military, so you should say that that is where the money goes.

https://en.m.wikipedia.org/wiki/Expenditures_in_the_United_S...


And we had multiple covid vaccines within under a year, with holdups being studying effects and approvals. While I agree we overspend on military, I don't think there's evidence spending more money would have improved the covid vaccine situation.

Then the opposite would be true? Less money we would have got the same outcome. Slightly nonsensical.

We need time and more people looking at the issue = money.


This – a thousand times, this.

I spent 5-6 years dealing with something like long-covid (only it started before covid). It had symptoms that seemed clearly related to an infection, but I also noticed effects that were similar to Alzheimer/dementia. Specifically sundowning.

I would become unthinkably exhausted and my mood would change drastically between the hours of about 5:00 and 8:00pm. Later in the evening, things would magically start clear up and I'd feel closer to normal.

That was, by far, the worst period of my reasonably long life, and it's still not something I'm over, I can just manage it much better. If anyone is dealing with something similar, I'm happy to talk about things that have worked for me.


I have read weird statements by people who had ALS. Some patients tell that some of their symptoms are seasonal. I am curious what worked for you? Thanks!

Curious as well as to what worked for you. I might have a milder version of what you have. Very similar in that it’s mainly during 5-8pm


> The model fit for those eligible for the shingles vaccine predicts the risk of dementia decreases with age. Come on.

Except that's not what the chart he included shows.

1. That chart shows a strongly positive age correlation in the non-vaccine-eligible group: dementia diagnoses go up as you get closer to the left edge of the chart. X axis is birthdate, not age, so the left side is older.

2. The right half of the chart shows a relatively flat relationship between dementia diagnoses and age, very slightly negative age correlation. It's plausible that more data would show a slightly positive age correlation with dementia. Visually, it appears that if you omit the 6th point on the right side of the cutoff date (assuming that it's an outlier), the trend would be weakly positive with age.

3. The charts show _new dementia diagnoses_, not total rate of dementia, and I don't think it's actually that unreasonable to think that your risk of a new diagnosis might go down with age beyond a certain point. Assuming that dementia is a permanent condition (i.e. once you get it, you have it until you die; probably close enough to true for this argument), anyone previously diagnosed with dementia would be ineligible for a future new diagnosis. So long as the diagnosis rate is positive, your probability of having dementia for a given age will be higher for higher ages. As an analogy, your risk of a new diagnosis of type 1 diabetes goes down after about age 14, yet it's not illogical to expect that a higher proportion of 20-year-olds have T1D than 14-year-olds.


I don't think the slope of the line is damning but if there are outliers that throw the slope that much off, that may be a sign there's not enough data.

Also if you change the slope the effect size diminishes because the left side of the line tips up.


This would not explain the precipitous rise in Alzhemier's rates seen in developed countries and mostly in the last few decades. I maintain that alzheimer's is type 3 diabetes.

There's a precipitous rise in old people, and especially otherwise healthy old people in developed countries. All those who would have died of perhaps an upper respiratory disease or an untreated infection before they had a chance to develop Alzheimer's are no longer being eliminated early. We see similar trends for most age related diseases like cancer and heart disease. It's only natural that as we get better at dealing with diseases we can cure we would see more of the ones we can't. That's not to say there couldn't be other environmental factors at play, but a rise in Alzheimer's does not necessarily mean a rise in whatever causes Alzheimer's.

> All those who would have died of perhaps an upper respiratory disease or an untreated infection before they had a chance to develop Alzheimer's are no longer being eliminated early.

OP claimed a rise in rates, not absolute numbers. Is there any plausible reason that reducing other causes of mortality might possibly cause a rise in fraction of the elderly population that develops Alzheimer's?


Depends if they meant rates or rates by age. If you mean population rates, then rising life expectancy caused by a decrease in other causes of death would absolutely increased overall pop alzheimer's rates.

If other causes of death were eliminated, you might also see an increase in alzheimer's amongst those in the same age bracket. This might be clearest with an example.

Suppose we eliminated heart disease. Life expectancy would increase. What would happen to the rates of other disease? They would go up within age groups. Because you still have to die of something. If heart disease can't take someone out, that means some other factor will be available. Much of the time people have more than one condition.


Depends on if the rise is specifically in the fraction of the elderly population, or if it's in the fraction of the general population.

If the rise is in the fraction of the general population, then an increase in the proportion of the general population that was elderly would be expected to increase the numbers of a disease of the elderly, even if nothing was happening.

If there were a rise in the proportion of e.g. 80 year-olds that were developing Alzheimer's, that'd be a different story. Although you'd still have to ask yourself if some of the conditions that were increasing the proportion of the population that are 80 year-olds were disproportionately extending the life of people with a propensity for Alzheimer's.


And this effect produces an increase in rates. Let's say that an entire population gets two dice. They roll the first one, if it's even they're out, otherwise they roll the next one. About 1 in 12 people are going to roll a 6 on that second dice. Now let's say for that first dice, you're only out if you get a 6. Now the odds of getting a 6 on the second dice is about 1 in 7, not because the second dice is any more likely to get a 6 but because a greater percentage of people who would roll 6's are rolling that second dice. The first dice in this analogy are diseases that we can now deal with, the second dice are the more intractable diseases.

It doesn't have to be mutually exclusive. Metabolic syndrome causes all sorts of general havoc with just about everything you can think of, which would probably include neuron's ability to maintain homeostasis or fight a latent infection.

Most everyone (at least older people who never got a chickenpox vax) has a latent varicella zoster (the shingles/chickenpox virus) infection, but only a minority will get Alzheimer's. It could easily be true that varicella is causal in most Alzheimer's, but also that many of those cases would never have happened without compounding risk factors like metabolic syndrome.


We’ve had rises in herpes viruses in developed countries. Shingles is a type of herpes virus. So I wouldn’t be too quick to make that judgment. Also in an aging population, it would have to be a relative rise in Alzheimer’s, not an absolute one. I don’t know the data, so I can’t say which it is.

But Alzheimer’s is a complex disease, it may well be there are multiple factors involved. I also am inclined to think there’s something to your hypothesis, there is some data to support it.


I almost brushed off your message at first, but decided to look it up. You have now made me aware of something I had never heard of, thanks!

https://www.verywellhealth.com/why-is-alzheimers-called-type...


It’s a bunch of crap. Maybe shouldn’t look for medical information from a social worker on a clickbait site.

Diabetes (specifically Type 2) is correlated with Alzheimer’s - how that makes for a useful new classification of diabetes is nonsense.

This would be about as sensical as calling nicotine addiction Type 2 lung cancer.

It also doesn’t help

> However, classifying Alzheimer's as type 3 diabetes is controversial

No, not in the medical community it isn’t. That there are some crackpots and quacks out there doesn’t change that - there is not serious debate ongoing about this in medicine.

It wouldn’t be a viable name anyway as the number 3 has already been reserved/in common use in actual clinical and research practice for pancreatogenic diabetes.


>> precipitous rise in Alzheimer's rates in developed countries

Besides the older human demographics, it's certainly possible the virus strains are evolving to be more aggressive and cause problem more often. From a virus perspective, it wants to be as viral as possible without killing the host. Alzheimer's seems like a reasonable allowance.


It might explain it if herpes is implicated..

> I maintain that alzheimer's is type 3 diabetes.

With type 1 diabetes there is growing evidence that coxsackievirus B virus is somehow involved.


Better diagnoses, more funding for diagnosis, more general knowledge of x, more sensitive tests for Alzheimer's. Those are the most likely culprits whenever you see a "oh no, rates are going up" headline. True for autism. True for this.

You don't believe that our foreign environment has something to do with it?

Pollution probably plays some role. Autism is multifactorial in its causes.

AFAIK the rise in Alzheimer's was well correlated with the rise in life expectancy.

https://www.medscape.com/viewarticle/975400 is interesting and seems to directly contradict what is claimed here.

"Herpes zoster does not appear to increase dementia risk ― on the contrary, the viral infection may offer some protection, a large population-based study suggests."


The evidence in the parent study is MUCH stronger than the evidence in the study you link (and is newer).

Science advances.


If you read much of the more recent literature, you'll see that the reference you cite is an example of how wrong science can be at times. However, even those mistakes, and the healthy debates they inspire, are important for progress over time.

Sounds like we should try to eliminate all long term infections just to be sure, even if they seem mild or harmless.

I wonder if 100 years from now people are going to be astonished that we were walking around full of bacteria and viruses and thought it was fine.

Haven't our digestive system co-evolved with a ton of bacteria? Wouldn't we be pretty boned if we just kicked them to the crub?

Yes, and having the right bacteria in the wrong place, or too much of the right bacteria, can be life threatening.

going beyond this, complete speculation but I wouldn’t be surprised if there can be benefits to these long-term viral infections alongside their harms

perhaps improving immune protection against more immediately harmful viruses, for example

IANAD though. I could be completely wrong


Sterile environments are actually bad. So what'll probably be astonishing is our lack of knowledge about how these viruses and bacteria shape our lives for good and bad.

More likely, they will be astonished that we managed to survive so long while still perceiving the natural world in a reductionist manner instead of noticing the symbiosis and holism that characterize and sustain it.

Many of the bacteria are certainly necessary. Healthy gut flora is very important. The viruses probably not.

Without viral help, none of us would be here to have this conversation.

Retroviruses control gene expression in pregnancy - https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6177113/


I had never heard of endogenous retroviruses before! They raise the question: if a virus writes itself into the genome, is it even a virus anymore?

I occasionally imagine what it would be like to wake up after being cryogenically preserved, be told that they'd fixed your <top ten cause of death>, and then being given a list of everything else that was wrong with you that you didn't even know was a thing.

Well, our bodies don't work without a ton of bacteria. Its fundamental to who we are. Clearly some are not beneficial, but getting rid of bacteria in general would be catastrophic.

There’s probably quite a few specific viruses and bacteria people 100 years from now will be astonished we just lived with in our bodies, but it seems unlikely that having a lot of bacteria and viruses in general will be seen that way. I guess it’s possible that we will develop non-bacterial alternatives to the beneficial bacteria and viruses that exist, but it’s not clear what the advantage would be.

until then, I will enjoy my yogurt

There are about as many bacterial cells in your body as human cells, so they could just as easily say the inverse.

39 trillion bacteria 380 trillion virii 100 trillion human cells

In any highly nonlinear system it's extremely difficult to predict side effects of changes like this. It's plausible there are benefits to things that seem mild or harmless and eliminating them can have dramatically negative consequences.

Summary: Wales used a cutoff date in 1933 to set eligibility for the vaccine: born before, ineligible; born after, eligible. The authors analyzed dementia rates in the populations born one week before and one week after and found a significant decrease in the vaccination population born one week after.

Given the unlikelihood of any other salient differences in the two populations (they were all born within 14 days of each other), they conclude that the vaccine had prophylactic effects against dementia and further conclude that Alzheimer’s may be caused by a virus.


Only in women, per the tweets.

Women get Alzheimer at a much higher rate, and it's not clear why. Perhaps this could be related.

This would make sense if Alzheimer's turns out to be an autoimmune disorder. Women have higher rates of these types of diseases because the largest number of immune related genes are found on the X-chromosome, giving them a broader variety to their immune arsenal. So women are better able to fight off infections but more likely to suffer from overactive immune responses.

A summary with some links: https://www.healthline.com/health-news/women-have-stronger-i...


Maybe because they have longer life expectancies and are less likely than men to die in most (all?) age brackets? Their husbands have died of heart disease before they get Alzheimer’s.

Those sound like easy variables to control when you're trying to determine which sex is more affected.

The vaccine was the shingles vaccine and it was administered in 2013.

The mechanisms of schizophrenia inside the brain also look alot like an inflammation or otherwise a kind of an infection immune system response, though an over-reaction. I'm making a broad characterization, of course.

The parasite toxoplasma gondii was initially noticed to be present in lots of folks with this type of mental illness (and bipolar) but there hasnt been a 100% correlation.


Massive hidden variable possibilities. Scientific discipline has been shitty for so long. It's exhausting. Beyond that, I wouldn't exactly call a 20% reduction evidence of direct cause.

Care to explain what hidden variable differentiates people born before vs after this exact date?

In short:

- Wales imposed an arbitrary hard cutoff (1933-9-2) on shingles vaccine, giving excellent randomization in a natural experiment

- Randomization confirmed by comparison of preëxisting conditions

- Individuals born after Sept 2, 1933 show a noticeable discontinuity in dementia diagnoses compared to those born prior to Sept 2, 1933, as seen in Figure 3

- Analysis indicates a 20% relative risk reduction across several types of dementia from receiving the VZ vaccine.

This is not like the EBV–MS connection: nothing in the stats so far suggests that varicella zoster is essential or nearly so to developing Alzheimer's disease or other dementia, but it is strong evidence that it contributes to the development of dementia.


I see the theory is based on the 2 Sept 1933 birth prior and after. And after meant they were eligible for the shingles vax. But not all born after that date got that vax. So what does the data show for born after 2 Sept and vax vs no-vax?

The no-vax born after 2 Sept should be very similar to born before 2 Sept, yes? Seems odd they didn't cover that base.


I wonder if there’s some kind of connection to the APOE4 genotype?

The connection is probably that ApoE4 carriers clear out amyloid beta deposits less efficiently than ApoE3/2 carriers (see e.g. [1] among many other sources), whereas microbial infection can induce amyloid deposits to form in the first place (see e.g. [2]), although it's not the only mechanism which can induce such deposits.

[1] Castellano et al (2011). Human apoE Isoforms Differentially Regulate Brain Amyloid-β Peptide Clearance. https://doi.org/10.1126/scitranslmed.3002156

[2] Eimer et al (2018). Alzheimer’s Disease-Associated β-Amyloid Is Rapidly Seeded by Herpesviridae to Protect against Brain Infection. https://doi.org/10.2139/ssrn.3155923


The most interesting thing that I saw was: "We find strong protective effects of the vaccine for women but none for men, and that this diff is driven by Alzheimer’s (not vascular) dementia."

I've been meaning to get around to getting the shingles vaccine. I was all set to head out the the pharmacy to get it immediately until I read that..


Get it anyway, you don't want shingles.

Yeah Shingles is awful.

Even a mild case sucks a lot.

You have to be careful how you read that. The researchers did not find that the shingles vaccine does not protect men (from dementia caused by Alzheimer's). They failed to find statistically significant evidence, in their studied population, that the vaccine protects men.

As the preceding sentence says, this can be plausibly explained by the fact that shingles is more common in women, so whatever protective effect the vaccine has is larger and more measurable.


The paper found absolutely no effect in men. That is to say: No trend nor indication that it might protect men.

Sometimes trends seem suggestive of a real effect, but don't rise to statistical significance. That is not the case here.

This is in Figure 4 of the preprint.


It could also be that there is a potential effect that this study would have been underpowered to detect, and by chance no trend was visible in this population. That's not inconsistent, or even particularly unlikely, if I'm understanding it right.

(A) To suggest that the lack of effect in men is a statistical anomaly, and that there IS an effect we're not seeing.

(B) To suggest that the effect in women is a statistical anomaly, and that there's nothing there but a fluke.

These things, from the data, are approximately equally likely. Because there was zero effect in men -- in fact, men who took the vaccine were apparently more likely to be diagnosed with Alzheimer's, though this trend was extremely slight.


> These things, from the data, are approximately equally likely.

They aren't. The paper states that 95% confidence interval for men includes a maximum protective effect of up to -1.9 while the 95% confidence for women include a minimum effect of -1.3.

Thus it is far more likely that there is a protective effect for man than no protective effect for women.


Are you ignoring the fact that it might have a negative effect, rather than a protective effect?

The range for men is -1.9 to +2.1 -- which averages out to +0.2 -- which indeed makes it seem as though the vaccine's trend is to make one slightly more susceptible to Alzheimer's, rather than less susceptible, which is itself borne out in the figure's trend line. (Fig 4.)

For women it's -5.3 to -1.3.


>Are you ignoring the fact that it might have a negative effect, rather than a protective effect?

Nope. We can be 95% confident that there is an effect for women but we can't be 95% certain that there is no effect for men.

Given that the error ranges overlap, we don't even have a high level of certainty that the effect for men doesn't equal the effect for women.

> The range for men is -1.9 to +2.1 -- which averages out to +0.2

Technically it averages out as +0.1


> we can't be 95% certain that there is no effect for men.

They're at P=0.93 right now. So they're very close.

Whereas, for women, P=0.0013.

Taking everything into consideration, that's exactly what I'd call "a high level of certainty that the effect for men doesn't equal the effect for women."


> They're at P=0.93 right now. So they're very close.

A big P value is bad.

> that's exactly what I'd call "a high level of certainty that the effect for men doesn't equal the effect for women."

Then you are operating off a non-standard cutoff for certainty because the paper explicitly states that the difference between the effect on male vs female is only statistically significant for the sub category of Alzheimer's.


Doesn't this mean that the chance of a true but unobserved -1.9 magnitude effect in men is much greater than the chance of a true but unobserved +0.0 magnitude effect in women?

Sure, but, by the same token, it also means that there's a chance of a true but unobserved +2 magnitude effect in men.

That means there's a decent chance that the real effect in men is in the range e.g. [-1.9, -1.0] but this study was unlucky or underpowered in men to see that effect.

this isn't necessarily true. if the study had 1000 women and 100 men, it would be a lot more likely that the result in men was wrong. similarly, if the effect was 20x weaker in men than women, but still existed you would be much more likely to see no effect in men even though effects existed for both.

Total study size was 282,541 people, 128,322 men and 154,218 women.

From supplementary material 1, page 27: https://www.medrxiv.org/content/10.1101/2023.05.23.23290253v...


Not necessarily true in a theoretical sense, sure.

But there's absolutely no indication that they enrolled 10x (or even 2x) more women than men. Nor is there any indication of any effect in men, 20x weaker or otherwise. (If we're charitable, it's pretty much a flat zero.)


Also, the study was based on the Zostavax, the live virus shingles vaccine. It was discontinued in 2020 (at least in the US) in favor of Shingrix which doesn't have live virus. Unclear whether Shingrix will have the same effects, though seems reasonable to think it might.

So you're hesitating to get the shingles vaccine because you found out it might not protect you against dementia? Don't you want to be protected against shingles?

You should get the vaccine. Shingles is awful.

That seems like a big deal!

Related reading on this topic: https://www.hardtowrite.com/pathogens/


At my annual mandatory physical yesterday my doctor told me that there's a new shingles vaccine that's around 90% effective as opposed to the 60-70% effectiveness of the previous vaccine. It's a two-shot vaccine as opposed to the single shot for the old one. I turned it down, but will probably ask for it now. I got the previous vaccine a few years ago, and then got shingles a few months later, although it was a fairly mild case and I assume that the vaccination probably had a positive effect on that outcome. The funny thing is that I recognized the incident as shingles, and called for an appointment immediately and informed them of my suspicion. At my appointment two days later the doctor prescribed some anti-viral pills and said they were best started immediately after recognizing the infection. I started laughing, as did he.

Shingrix is the "new" one but it's been on the market for several years.

The shingles vaccine that I got 4 years ago was a two-shot vaccine. Is this another new(er) vaccine?

No. Shingrix is the most recent shingles vaccine, AFAICT. It requires two injections for folks age 50+ or with weakened immune systems. Zostavax required one, but was withdrawn from the US market in 2020.

Is there any benefit to getting the vaccine after you've already gotten shingles?

You can get shingles again.

Yes, shingles is reactivation of latent herpes zoster (chickenpox) usually acquired in childhood. The vaccine prevents these reactivations You can have shingles multiple times, and some people are more prone to recurrences.

Clearly it doesn't, given that semidetached just said he took the vaccine and then within months got shingles.

One counter example does not disprove the substantial studies that show a strong percentage of cases that are avoided.

He also stated that he had a mild case. Trust me, shingles can be extremely unpleasant. Any level of protection from the vaccine is worthwhile.


Yes. Risk of Shingles doesn't decrease after an outbreak (sadly).

Very interesting. I recently watched the Michael J. Fox documentary(Still) and even he commented on an earlier infection as a teen "could've" been linked to his condition, but we'll never know.

Also having gone through two extended bouts of long covid now, I think it reactivated a family history of rheumatoid arthritis in me temporarily although I've never formally been diagnosed with it or struggled with it.

We're all just walking balls of disease causing germs eh?


The thing with Fox is that there were four people on the same TV or movie set that all wound up years later ill with Parkinson's.

But it's such a rare illness that most people who have it won't have ever met someone else with it before they got sick. For four people who all worked together to have it, it's a statistical anomaly if the disease is purely by chance.



> When asked about the cluster by Howard Stern in a September 25, 2013, interview on The Howard Stern Show, Michael J. Fox stated, "Believe it or not, from a scientific point of view, that's not significant."

I thought Fox wasn't being accurate, but if you do the math on that, he's not wrong.

Parkinson's hits about 1 in 300 (0.33%), and that cast saw 4 out of 125 (3.2%). That sounds like it's a crazy amount more, but if you pop those numbers into an A/B test calculator, it's borderline whether you consider it significant or not, because the small sample size really reduces the statistical power.

It's definitely interesting but it's not wrong to say that it isn't significant by some statistical measures.


There's a lot of weird disease stuff going on. There was an article on how schizophrenia is linked to some multi million year old retrovirus that hangs out in our genome.

Been a while since my reading on the subject, but maternal flu infection during pregnancy has been linked to development of schizophrenia, too.

This seems like a math artifact caused by splitting into two groups and then curve fitting the two groups separately. Those two curve fits don't line up at the discontinuity but there's no reason to expect that they would.

The image in tweet 8 is really the damning one. It shows a big gap, but if you fitted the entire set it'd be nearly a straight line with a tiny blip caused by the vaccine.


Regression discontinuity

Will be interesting to see the study go through the peer reviewed process & whether it will be published by a journal.

Yet another reason to try to avoid getting infected with diseases. A 'stronger' immune system (which is really only 'stronger' at defending against the disease that you just caught!) isn't worth the risk of long-term side effects from a chronic infection.

Immunity not having challenges, especially early in life, is a sure recipe for a miserable life full of allergies (and probably more, autoimmune problems are a vast domain).

Not sure I would want to take a small risk of topic discussed with almost sure chance of this. Maybe some form of risk is unavoidable, and part of life. Of course only till we fully crack our dna manipulation without any side effects, but thats 22nd century stuff at best.


Environmental, non-disease challenges are important to develop proper immune response. Catching the flavor of the day does jack all, and might actually prompt some autoimmune responses and lymphomas (due to the increased activity of the immune system in response to infection).

People who never acquire a chronic herpes zoster infection are highly unlikely to benefit from a shingles vaccine with respect to this sort of dementia.


It kind of depends?

For things like Chickenpox, it’s far better to be infected young (where it’s a mild disease) than old (where it can be quite severe).


It's even better to get vaccinated so that any infection has much decreased odds of becoming a chronic latent infection. Vaccinate enough people and eventually people may not get infected at all.

> which is really only 'stronger' at defending against the disease that you just caught!

if this was the case, we wouldn’t have the smallpox vaccine, or many others. not to mention the massive increase in general disease susceptibility when children aren’t exposed to these agents at a young age


I don't understand what you are saying, because it appears to not follow what I stated. (Edit: Okay, I've got it now.)

A chickenpox infection as a child will indeed help prevent against future chickenpox infections (which, for this particular virus, are indeed worse when first infected as an adult). It may have some slight efficacy against other herpesviruses, too, or it could enable a stronger disease from a related virus due to antibody-dependent enhancement. But more likely a chickenpox infection, and related acquired immune responses, will do jack-all with respect to any other infectious agent.


> more likely a chickenpox infection, and related acquired immune responses, will do jack-all with respect to any other infectious agent

why is this?


Because most viruses differ enough that they don't have similar recognition motifs (antigens). Sometimes a lucky person will get a "universal" response to an entire viral clade, but at some point the clades just diverge enough that they can't offer protection against each other.

If you have to get infected with a pox virus, cowpox or chickenpox are good ones to get infected with. But it's better not to get any, if you have the option.


do you have a source for this?

Just my general training in biology. I work mostly in non-animal organisms, but recall enough of my education and what I read during the COVID pandemic. This is a complex topic, and I was simplifying above.

https://en.wikipedia.org/wiki/Cross-reactivity#In_immunology

This seems to be a good article on the benefits and limits of cross-reactivity: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3352416/

And here seems to be a decent review looking at Antibody-Dependent Enhancement, a key limitation of antibody cross-reactivity for viruses: https://www.sciencedirect.com/science/article/pii/S016158902...

Basically getting infected by some things can help provide protection against some other things, can make infection by some other things worse, or can have no effect on protection against other things. All in all it's generally better to not get infected by a particular thing, but if you're going to be exposed to worse things that infection by the particular thing provides protection against this is an exception.

A book chapter on infections causing, or curing autoimmune diseases: https://www.ncbi.nlm.nih.gov/books/NBK459437/

And a review article on the same: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6723519/

> Available data indicate that viral-induced autoimmunity can be activated through multiple mechanisms including molecular mimicry, epitope spreading, bystander activation, and immortalization of infected B cells. Contrarily, the protective effects can be achieved via regulatory immune responses which lead to the suppression of autoimmune phenomena.


> The smallpox vaccine is the first vaccine to have been developed against a contagious disease. In 1796, British physician Edward Jenner demonstrated that an infection with the relatively mild cowpox virus conferred immunity against the deadly smallpox virus. Cowpox served as a natural vaccine until the modern smallpox vaccine emerged in the 20th century. ...

> The term vaccine derives from the Latin word for cow, reflecting the origins of smallpox vaccination.

https://en.wikipedia.org/wiki/Smallpox_vaccine


Serious déjà vu did I not read about this study a year ago on HN? I can see this is recent in date but can't shake the feeling...

https://pubmed.ncbi.nlm.nih.gov/35434253/ perhaps this


I recently read some speculation that Alzheimer's might be related to prion diseases like wasting and mad cow disease. That's one possible explanation for cattle mutilations also, which is a really weird rabbit hole to go down.

I’m inclined to believe that the bulk of cattle mutilation cases are from natural predators and the really anomalous-seeming cases are just from thrill-seeking sociopaths and/including bored farmers, both groups undoubtedly encouraged by media attention

to go on a slight flight of fancy, I could believe one or two (perhaps early) cases were aliens. if you’re looking down from above in certain regions, the largest groups of exposed megafauna will be cattle. what do humans do when we meet an abundant new life form? kill one and cut it up to see how it ticks.

but then another plausible hypothesis is that it’s just a slightly sick inside joke/prank amongst some subculture, playing on that observation to mess with the credulous


“ 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.”

So only 47.2 % of the adults eligible to get the vaccine chose to get it. I am sure that those 47.2% are doing lots of health things right, like paying attention to their vaccine eligibility, for one. I imagine those behavioral differences in the eligible people who chose to get the vax and those who didn’t, could explain this pretty minor reduction in Alzheimer’s.

This would be more interesting if all the eligible adults got the vax, and all the ineligible ones didn’t.

Am I missing something?


They weren't measuring the effect of getting the vaccine directly, just the effect of being eligible for the vaccine. That is, they looked at rates of dementia by birthdate cohorts, not by got-the-shingles-vaccine cohorts.

If your hypothesis were correct, the vaccinated cohorts would have lower-than-population-average dementia rates, while the unvaccinated cohorts would have higher-than-population-average dementia rates. This wouldn't cause any measurable effect on the total dementia rate for a given birthdate, as presumably something like 47.2% of the population born just before Sept 2, 1933 would _also_ be doing lots of health things right.

That is, your hypothesis doesn't explain the data they found, which is not categorized by vaccination status, and showed that people born just after Sept 2, 1933 are significantly less likely to be diagnosed with dementia than those born just before Sept 2, 1933.


Oh I see. Hmm, it’s interesting although the effect seems small enough that I wonder if the true cause is something like “if you get a serious illness as a senior then you’re more likely to decline overall and that’s what contributes to Alzheimer’s.” Since Alzheimer’s also seems correlated with lots of other bad conditions, like T2D, sedentariness, low physical fitness, poor social habits, smoking.

I'm not sure if they are aware of all the variables. %20 reduction only on one gender does not make much sense to me.

That was strange to me as well. More women than men get shingles, but I’m not sure whether that difference is strong enough to explain the difference in the study.

My question is: What of people who have never had chickenpox in the first place, and have never been vaccinated for it? A substantial fraction, though still merely a fraction, of the UK population is in this category. (Back of napkin calculation, more than a million people aged 60+ in the UK.)

If herpes zoster is a causative factor behind Alzheimer's, and if the vaccine merely dampens the viral load (or some such thing) in people who carry it, then people who have never had it -- and have a HZ viral load of zero -- should exhibit a dramatically lower rate of Alzheimer's.


My family history has no memory of me having chicken pox. I had shingles at around 13. I was full vaccinated and still caught measles in 2011. The ages when I was receiving vaccinations was living in rural Florida.

I have shingles in my left eye, since 2017. It didn't go away because after after a year or 2 of dealing with it, a doctor suggested I get my immune system checked. Turns out my immune system is for shit (IgG levels got down to 80; they are supposed to be 600-1500). They don't know the cause.

If you had shingles at 13, you must have had chicken pox before that, because that's how it works: you get CP first, it lies dormant in your nerve ganglia, then comes out as shingles when you are stressed or your immune system is weak.

Since you said you were vaccinated against measles but still caught them, it sounds like you might have an immune system issue like me. My body doesn't make antibodies, so I have to take weekly infusions of human IgG. IgA and IgM are also not working, but those apparently aren't as important. And I don't think there is any treatment to supplement them anyway.

Suggest you get an IgG, IgA and IgM blood test. If your levels are really low, you could be a walking time bomb like me. I was lucky and never got really sick, but while I was at Mayo, the levels were so low (80), they sort of freaked out and didn't want to let me leave without taking an infusion.


Have you been taking valacyclovir?

I started acyclovir a couple of days after shingles broke out, in 2017. It calmed down after a couple of weeks, so they knocked it down from 5 pills a day to a maintenance dose. A couple of weeks later, it flared back up. This went on for several months.

I switched to valacyclovir, mainly because I only had to take it 2x a day instead of 5. Told my doctor (ophthalmologist) I think I needed it 3x/day, and instead of doing that, he lowered it to once/day. A week later, it flared back up, and he did put me on 3x/day. I found out 3 years later when I went to Mayo that 3x/day is the standard dosage for an active herpes infection. For the first couple of years, I didn't know my immune system was broken, and it took over a year to figure that out (because of a prostate infection I shouldn't have had at my age, that required 2 rounds of antibiotics - also unusual).

I was on valacyclovir for about 4 years, but went off gradually myself because I couldn't tell that it was helping me much. I switched doctors because of insurance, and the new one basically lets me guide my medicine dosage myself based on symptoms because of all the problems in the first few years.

If anyone does get shingles in their eye and starts using steroid eyedrops, make sure your doctor also puts you on an eye pressure drop. Mine didn't, because he said he "didn't get concerned until eye pressures got above 25". I was on huge steroid doses, like 8 drops/day, for many months without an eye pressure drop and it caused severe optic nerve compression. The guys at Mayo said it's standard practice to use an eye pressure drop (brimonodine) whenever a steroid is used, and that eye pressures should always stay between 11 and 14 to avoid that.

Doctors don't always know what they're doing...


>> My family history has no memory of me having chicken pox. I had shingles at around 13

Those are the same virus. Yours manifested as shingles even though you were only 13.


I have heard it both ways. Shingles at 13 is chicken pox and one must have chicken pox to have shingles.

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