[HN Gopher] Do viruses trigger Alzheimer's?
       ___________________________________________________________________
        
       Do viruses trigger Alzheimer's?
        
       Author : helsinkiandrew
       Score  : 174 points
       Date   : 2025-03-23 07:29 UTC (15 hours ago)
        
 (HTM) web link (www.economist.com)
 (TXT) w3m dump (www.economist.com)
        
       | helsinkiandrew wrote:
       | https://archive.ph/bxpk0
        
       | ekianjo wrote:
       | > Two other studies, one by GSK, a pharmaceutical company, and
       | another by a group of academics in Britain, also reported that a
       | newer "recombinant" vaccine, which is more effective at
       | preventing shingles than the live version, appeared to confer
       | even greater protection against dementia.
       | 
       | "confer" is something you use for a proven link with an
       | interventional study, not for some random link you found within
       | the thousands of variables you went fishing for in your
       | observation study dataset.
        
         | Mordisquitos wrote:
         | Hence why the article does not say that the vaccine _conferred_
         | protection against dementia, but rather that it _appeared_ to
         | confer protection.
        
           | ekianjo wrote:
           | appear to confer is a pretty biased wording. Rather, the only
           | correct way to write about it is "there was a correlation
           | that needs further investigation, we have no idea if there is
           | a causal link about it".
        
             | throwawaymaths wrote:
             | thr vaccine study is a pretty clear (partial) causal link.
             | there is a jump discontinuity in all causes dementia cases
             | based on week of birth, where the jump occurs at the NHS
             | policy cutoff week (if you are older than this week you are
             | ineligible fof the vaccine).
             | 
             | It's likely partial because vaccines only confer resistance
             | against one subset of virii and there may be nonviral
             | Alzheimer's too. in any case causality is not really in
             | question in that study
        
             | Mordisquitos wrote:
             | I do not see the bias, all the more so given that the whole
             | article after that first paragraph very clearly explains
             | that further investigation is taking place to determine
             | whether there is such a causal link. I have no idea whether
             | _conferring_ is a strictly defined term in the context of
             | clinical research, but even if it is this is not a
             | scientific journal article but aimed at the general public.
             | 
             | Going in detail to the claim that 'appear to confer' is
             | biased, even if we take such a strict understanding of
             | _confer_ , compare the semantic effect of affirming and
             | negating the sentence with and without 'appear to'
             | 
             | 1. _' the vaccines conferred protection'_
             | 
             | 2. _' the vaccines did not confer protection'_
             | 
             | 3. _' the vaccines appeared to confer protection'_
             | 
             | 4. _' the vaccines did not appear to confer protection'_
             | 
             | Which of the sentence above is closest to the truth, and
             | which is most inaccurate?
        
         | gus_massa wrote:
         | I agree.
         | 
         | Double blind randomized controled trial or it didn't happen.
         | 
         | Perhaps people with early symptoms are not given the vacine
         | because it's too expensive and not mandatory?
         | 
         | Perhaps people with the vaccine are younger becase it's a
         | recent vaccine?
         | 
         | Perhaps people that has no money for the vaccina had no money
         | for therapies to slow the sympthoms?
        
           | energy123 wrote:
           | Double blind randomized controlled trial with endpoints and
           | statistical methods disclosed in advance from a lab with a
           | reputation for publishing null results, or it didn't happen.
        
           | Mordisquitos wrote:
           | Penultimate paragraph of TFA:
           | 
           |  _' The first double-blinded randomised clinical trial to
           | test the effectiveness of antivirals against dementia is now
           | under way. A group of researchers mostly based at Columbia
           | University are testing whether valacyclovir, an antiviral
           | used against HSV1, can slow down cognitive decline in people
           | with early stage Alzheimer's. Between 2018 and 2024, the
           | researchers recruited 120 patients and treated half with the
           | antiviral. They expect to publish their findings later this
           | year. John Hardy, whose research forms the basis of the
           | dominant amyloid theory of Alzheimer's, and who has been a
           | critic of the virus theory, says that a positive result in
           | this trial would begin to convince him otherwise. If Dr
           | Geldsetzer and his team can secure the funding, a similar
           | trial of the shingles vaccine may soon follow.'_
        
             | apinstein wrote:
             | Oh wow, a bunch of Alzheimer's grants at Columbia were
             | canceled, including the Alzheimer's Disease Research
             | Center. Unclear if this study was affected...
             | 
             | https://taggs.hhs.gov/Content/Data/HHS_Grants_Terminated.pd
             | f
        
             | gus_massa wrote:
             | So... and unfinished RCT of an unrelated drug an a project
             | to start in the future a RCT of this new use of the
             | vaccine.
             | 
             | The problem is mixing the real protection of the vaccine
             | against shingles that has been tested in RTC and new
             | aplications that have not been tested enough.
             | 
             | If there are too many false provisional anouncements,
             | people will not thrust medicine.
        
               | Mordisquitos wrote:
               | The article opens describing how people vaccinated
               | against the HSV1 virus are statistically less likely to
               | develop dementia, and that a newer virus appears to
               | confer an even bigger effect.
               | 
               | The article then proceeds on the history of the
               | scientific debate on whether the HSV1 virus has a causal
               | link to Alzheimer's and the level of acceptance of the
               | hypothesis.
               | 
               | Finally, the article concludes describing how an RCT is
               | taking place to find whether an antiviral which is used
               | to treat HSV1 has an effect on the development of
               | dementia.
               | 
               | It all ties together with the theme of the article, which
               | is about the possibility that viruses may trigger
               | Alzheimer's and the reason why research is being carried
               | out in that direction. That open question is literally
               | expressed in the headline.
               | 
               | I honestly cannot understand the problem you are seeing
               | in the article. How else would you express the same
               | information?
        
           | throwawaymaths wrote:
           | > Double blind randomized controled trial or it didn't
           | happen.
           | 
           | This is just cargo culting. Read the original source paper
           | and you'll understand why the causal relationship makes sense
           | without an RCT.
        
             | gus_massa wrote:
             | Do you have the DOIs?
             | 
             | I found https://www.nature.com/articles/s41591-024-03201-5
             | 
             | They compare people that got the old vaccines in 2014-2017
             | with people that got the new vaccine in 2018-2020. Some
             | strange parts:
             | 
             | They say they are analyzing 6 years, but for the second
             | group the 6 years period has not ended. This makes the
             | comparison difficult.
             | 
             | These periods includes the covid-19 epidemic in 2020, with
             | lock downs, changes in death rates and new vaccines. This
             | makes any comparison difficult.
             | 
             | The comparison in figure "1 e" have very different initial
             | slopes. I'd expect dementia to be a slow accumulation of
             | small problems in the brain, so I'd expect an initial equal
             | slope and after some time a difference. They start the
             | comparison after 3 month, but I expect a slower effect.
             | 
             | Figure "1 f" has the same initial slope difference, but
             | there is also a strange slope change in d=1750 and the red
             | line is more noisy probably due to the unfinished 6 years
             | period).
        
               | kps wrote:
               | Preprint of the main paper on pubmed:
               | https://pmc.ncbi.nlm.nih.gov/articles/PMC10246135/
               | 
               | They rule out the objections in your top post -- as well
               | as whether people chose to get the vaccine, which would
               | be a huge confounder for a disease that affects
               | cognition.
        
       | roenxi wrote:
       | The part of these sort of conversations that makes me wary is
       | this understanding that "Alzheimer's" is a disease with a single
       | cause. I think it is beyond question that _some_ viruses trigger
       | Alzheimer 's, because viruses can do pretty much anything. The
       | real question that they're studying is _to what extent_ do
       | viruses cause Alzheimer 's. If it turns out that most Alzheimer's
       | cases are a Herpes symptom then that sounds big.
        
         | FollowingTheDao wrote:
         | I agree, it is very frustrating. I will say that the reason
         | they have not found a cause and/or cure for Alzheimer's is that
         | it is a polygenic and polyenvironmental disease. The only way
         | to cure Alzheimer's is to look at each person individually
         | (personalized medicine) but that is expensive and not as
         | profitable.
        
           | h0l0cube wrote:
           | So then "curing Alzheimer's" is akin to "curing cancer". If
           | this is true, I wish this truth was better disseminated.
           | 
           | Is the theory now that Alzheimer's just actual brain rot, of
           | which their are multiple causes, and that beta amyloid
           | plaques are just detritus of a losing battle?
        
             | chneu wrote:
             | Some researchers think Alzheimer's is a man made disease.
             | 
             | The last time I read up on this it was basically that we
             | all have some predetermined risk of developing an
             | Alzheimer's type disease, but that modern environmental
             | variables raise that risk to such a high likelihood that
             | it's become something it never used to be.
             | 
             | Interesting to think about.
        
               | peterfirefly wrote:
               | > , but that modern environmental variables raise that
               | risk to such a high likelihood that it's become something
               | it never used to be.
               | 
               | Well, yeah, because _more people get old enough to get
               | it_.
        
             | jononor wrote:
             | We have built a rather large toolset for detecting and
             | treating a range of cancer variants over the last decades.
             | With meaningful changes in expected outcomes. Considerable
             | drop in mortality, for example. Far from cured though.
             | Alzheimer's might be much trickier. ..
        
               | h0l0cube wrote:
               | I'm guessing it's trickier because it's harder to get
               | biopsies of the brain mid treatment. It doesn't help that
               | it's been treated as one disease and assuming a single
               | cause for so long
        
           | EasyMark wrote:
           | Do you have know of any individualized Alzheimers treatments
           | resulted in the cure, slowing down, or "stopped further
           | damage"? That would seem like big news, even if it was only
           | in a person or two.
        
         | tim333 wrote:
         | I wouldn't say the question should be "to what extent do
         | viruses cause Alzheimer's". I mean you could run a regression
         | analysis to find that and then what?
         | 
         | The real question is what is going on and how do we fix it?
        
         | pedalpete wrote:
         | The way I've looked at it (and I work in the adjacent space of
         | neurotech/sleeptech) is that it is likely we are assigning
         | multiple diseases with the label of Alzheimer's because we
         | don't understand the disease well enough.
        
       | elif wrote:
       | Do we really need questions as headlines?
       | 
       | It's bad enough that people fail to contextualize or deeply
       | consider the reality behind sensational headlines, but when you
       | open the door to vague questions as headlines, you are somehow
       | journalistically allowed to memetically plant a known lie into
       | the zeitgeist of the majority of internet users who read the
       | headline but dont click to read the article.
        
         | Mordisquitos wrote:
         | I would agree if the article was an example of Betteridge's law
         | of headlines [0], but in this case it is legitimately
         | reflecting the overall message of the article, which is that it
         | is becoming an open research question in science whether
         | viruses trigger Alzheimer's having previously been a fringe
         | hypothesis.
         | 
         | The very fact that the last sentence of the article is
         | expressed as a conditional is also consistent with the use of a
         | question for the headline:
         | 
         | > _' If antiviral treatments can indeed slow, delay or prevent
         | even a small subset of these cases, the impact could be
         | tremendous.'_
         | 
         | [0] https://en.wikipedia.org/wiki/Betteridge's_law_of_headlines
        
         | tim333 wrote:
         | We don't need them but I don't see a problem either if they are
         | appropriate to the article as in this case.
        
       | A_D_E_P_T wrote:
       | Very interesting.
       | 
       | Memantine is an antiviral/nootropic (NMDA agonist) that's
       | considered one of the best conventional therapies for
       | Alzheimer's. For e.g., https://pubmed.ncbi.nlm.nih.gov/32914577/
       | 
       | Amantadine is a related compound that's seemingly more potent as
       | an antiviral, and less potent at the NMDA receptor.
       | 
       | Medical hypothesis: This makes me wonder if amantadine might be
       | an effective drug in Alzheimer's treatment. It would come as a
       | total shock to the med chem community if memantine's activity had
       | to do with its suppression of viral replication, and much less to
       | do with its activity at the NMDA receptor.
       | 
       | As an aside, the Russians have a similar drug called bromantane
       | which is sold OTC as a sort of mental energy booster. It's not
       | really a stimulant, and its effects are mild enough for daily
       | use. It might also be very interesting in this context.
       | https://en.wikipedia.org/wiki/Bromantane
        
         | johnisgood wrote:
         | I believe most nootropics work for Alzheimer's, probably
         | Huperzine A, too. Perhaps even Noopept.
         | 
         | NMDA agonists and acetylcholinesterase (they inhibit the
         | breakdown of the neurotransmitter acetylcholine) in general.
         | 
         | Benadryl (DPH) and first-generation antihistamines are the
         | opposite of that, they can cause delirium (and it messes up
         | your memory and cognition in general) and whatnot, they are
         | anticholinergic, some more than others. I had anticholinergic
         | toxicity from DPH before.
         | 
         | I take Alpha-GPC (a very soluble form of choline) and Huperzine
         | A for cognition / memory, others couple it with racetams (e.g.
         | piracetam, pramiracetam, aniracetam, etc.).
        
           | TechDebtDevin wrote:
           | My primary care doctor is telling all of her patients not to
           | take Zyrtec for an anti-histamine because it is causing
           | dementia side effects in her older patients. Antecdotal but
           | interesting.
        
             | johnisgood wrote:
             | For the reasons I mentioned, yes. :)
             | 
             | But Zyrtec is second-generation. It shows 20,000-fold or
             | greater selectivity for the H1 receptor over the five
             | muscarinic acetylcholine receptors, and hence does not
             | exhibit anticholinergic effects, so it should be OK. May
             | still cause drowsiness, however.
        
         | jadbox wrote:
         | I've had some experience here and will add a couple notes.
         | 
         | Memantine has been useful for slowing down Alzheimer's and
         | temporarily improving responsiveness. However, Memantine has
         | not shown any effectiveness in reversing Alzheimer's or fully
         | stopping its progression (sadly). Memantine does seem to
         | increase self-awareness clarity but, counterintuitively, seems
         | to also disrupt memory recall. Word of caution, in one rat
         | study, I had read that Memantine could have long term side-
         | effects of hindering memory recall.
         | 
         | Amantadine has a fascinating structure, but it seems like it's
         | not super useful by itself from studies. It seems more like a
         | very promising 'base structure' to build future compounds upon
         | (like Memantine and bromantane).
         | 
         | Anyways, this family is rather interesting for a number of its
         | properties and are still not very well known or understood.
         | Please do share any more insights.
        
           | A_D_E_P_T wrote:
           | Random notes:
           | 
           | - Unlike amantadine, chemically-related tromantadine is
           | potently effective against HSV.
           | https://pmc.ncbi.nlm.nih.gov/articles/PMC185716/
           | 
           | - There's another paper which may shed some light on the
           | herpes-Alzheimer's connection, and it notes that treatment
           | with tromantadine (among others) is starkly beneficial:
           | https://pmc.ncbi.nlm.nih.gov/articles/PMC5935641/
           | 
           | - If the connection is established, it could be that a
           | tromantadine-like molecule with activity against herpes
           | simplex -- _plus_ mild activity at the NMDA receptor reducing
           | excitotoxicity and protecting neurons -- could potentially be
           | a good prophylactic against Alzheimer 's.
           | 
           | - It would be interesting to test amide-linked amantadine-
           | phenylalanine and memantine-phenylalanine conjugates. Such
           | things would probably penetrate the BBB very well, as they
           | could take advantage of amino acid transporters. (The LAT1
           | transporter in particular.) And they resemble tromantadine --
           | where it is said that the amide itself is a necessary moiety
           | in countering HSV. Structure:
           | https://i.ibb.co/7tS4MGGL/Amantadine-Phe.png
        
             | DrAwdeOccarim wrote:
             | Are you a drug developer by trade? You certainly think like
             | someone who's seen some SARs...
        
         | chriscappuccio wrote:
         | Memantine is an NMDA antagonist like ketamine and other
         | dissociatives.
        
         | TechDebtDevin wrote:
         | My doc put my on amantadine for post covid symptoms and I felt
         | like it gave me mild dementia and had to stop :/
         | 
         | edit: Fun fact, the side effects were so bad I made a very big
         | mishap that destroyed a (very very expensive) f-class flight
         | simulator.
        
       | nraynaud wrote:
       | It's really surprising that with all the statistical tools we
       | have, the signal for the link between a common virus and a
       | disease is unclear. Even if the road to a proven intervention is
       | long, you'd think at least the link would be clear.
        
         | tim333 wrote:
         | I think the link has shown up in the statistics for a long
         | time. The article mentions Ruth Itzhaki being on it for 40
         | years. But things seem delayed by something along the lines of
         | politics/corruption, or by the complexity of the situation with
         | HSV1 not being the only cause. It can become a mess
         | https://www.nytimes.com/2025/01/24/opinion/alzheimers-fraud-...
         | 
         | I'm hoping that AI helps sort this stuff out. It can read the
         | papers and say hypothesis A is most likely even if professor Y
         | had built an empire on it being hypothesis B.
        
           | giantg2 wrote:
           | HSV1 is estimated to affect more than 80% of the population,
           | but less than 80% have dementia. This seems to imply there
           | are other factors at play. Maybe it requires other factors
           | like genetics or immune issues for it to progress.
        
             | amanaplanacanal wrote:
             | I can't point to a citation but I'm sure I've seen it
             | hypothesized that it requires both the infection, then some
             | sort of injury to allow the virus to cross the blood brain
             | barrier.
        
         | bognition wrote:
         | The issue is that we don't have the primary data. This stuff is
         | messy and the systems at play are extremely complicated. Often
         | one of the most challenging parts of bio sciences is figuring
         | out a test that will cleanly show a result that is true.
         | 
         | Without directly testing for a connection it's extremely rare
         | to get unexpected data that confirms an alternate hypothesis.
         | 
         | Even if the statistical tools are there, they can't make up
         | numbers that we haven't collected yet.
        
         | readthenotes1 wrote:
         | With Alzheimer's, it's possible that it's fraud hiding the
         | linkage.
         | 
         | E.g., https://www.science.org/content/article/potential-
         | fabricatio...
         | 
         | https://www.science.org/content/article/research-misconduct-...
         | 
         | https://arstechnica.com/science/2024/07/alzheimers-scientist...
         | 
         | https://stanforddaily.com/2023/02/17/internal-review-found-f...
        
           | lttlrck wrote:
           | > Authors sometimes share those with researchers conducting
           | similar work, although they usually ignore such requests,
           | according to recent studies of datasharing practices.
           | 
           | If the research was in anyway paid for with federal dollars
           | all this data should be public. Not only that, if true it is
           | a waste of federal dollars.
           | 
           | It's probable that the widening mistrust in science is due to
           | this a sort of behavior and the resulting administration.
           | 
           | Waste due to inefficiencies is one thing, waste due to fraud,
           | data hiding, misdirection is something else.
        
         | giantg2 wrote:
         | The part that might not be clear could be due to other factors,
         | such as a genetic or lifestyle component that cause this to
         | only progress to disease in some individuals.
        
         | crazygringo wrote:
         | The article clearly explains that the link isn't clear at all.
         | 
         | It's that certain damaging proteins are a line of defense
         | against the HSV1 virus, that something _sometimes_ sends those
         | proteins into overdrive, that this is influenced by genetics
         | broadly, further influenced by a particular gene, and that it
         | 's a _second_ infection with shingles that can reactivate the
         | proteins, worsening it.
         | 
         | Given that this is the interplay of something like at least 5
         | factors, and there may be more, it's not surprising it's taken
         | this long to put together, even with all our statistical tools.
        
         | epidemiology wrote:
         | It's not that we haven't thought up the statistical tools. The
         | core theoretical tools you need are there. It's that gathering
         | the data that you need is extremely difficult and time
         | consuming.
         | 
         | If you gather EHR or medical claims record data for vaccines
         | for example, you have to take very seriously the biases and
         | impact of missingness inherent in the data. Is that person you
         | have no evidence of disease for truly not diseased or do they
         | just have missing data? IS it missing because they just didnt
         | go to the doctor because they're healthy enough to kick the
         | disease on their own or because they're so financially unstable
         | that they can't afford to consistently see their primary care
         | doctor. Is the data missingness itself actually what's more
         | correlated with the disease than the vacciation you are looking
         | at?
         | 
         | Example: If your outcome is dementia then may be using
         | cognitive tests that have a high level of variability due more
         | to social class, education, test taking ability. Is receiving a
         | fancy vaccine is more likely in an affluent area? Could be that
         | correlation itself might completely explain away the positive
         | effect that vaccine has on cognitive test scores.
         | 
         | In Alzheimer's you're often trying to correlate things that
         | happen in early life with long term damage that only surfaces
         | many many years later. Retrospective studies where you go back
         | and ask sick or healthy people have recall bias where the sick
         | ones remember more issues with themselves early on than healthy
         | ones do even with the same early life issues.
         | 
         | Not trying to say epi is perfect or that there isn't room for
         | improvement in tools (there absolutely is). But just like often
         | happens when crossing over into the biological sciences there's
         | a lot stickier problems than people outside the field realize.
        
           | nradov wrote:
           | Right, the data quality is usually crap. Beyond the issues
           | you mentioned, patients often switch providers or health
           | plans and their data doesn't get migrated. In the USA at
           | least there is no centralized national repository for that
           | data so the further back you try to go the more likely the
           | data will just be missing (or incorrectly coded). In theory
           | there are interoperability APIs and national networks to
           | solve this problem but in practice a lot of systems still
           | aren't properly connected.
           | 
           | For vaccinations specifically the CDC Immunization Gateway
           | can be a good place to start. Most states also maintain their
           | own immunization registries that can be queried through
           | standard HL7 V2 Messaging and/or FHIR APIs if you have the
           | appropriate permissions.
           | 
           | https://www.cdc.gov/iis/iz-gateway/index.html
        
         | bkfunk wrote:
         | Once I started learning more about biology, I realized that
         | everything is just so complex. The body repurposes chemicals a
         | lot, so you have things like serotonin being a key
         | neurotransmitter in the brain, but also in the gut. And you
         | have enzymes that are coded in genes, but then there are also
         | networks of genes that are up- or down- regulated by hundreds
         | of other genes, and sometimes only in certain types of cells or
         | certain physiological environments. And then of course there
         | are epigenetic and immune-modulated effects at the genome, gene
         | network, and individual gene levels. Not to even mention all
         | the feedback mechanisms and meta-feedback mechanisms (the drive
         | toward homeostasis is POWERFUL), and effects of countless
         | chemicals in our environment.
         | 
         | There are certainly clear-cut cause-effect relationships in
         | biological systems, but even they will have edge cases and
         | random chance to muddle the picture.
         | 
         | I would posit that the human body is far more complex than even
         | the largest codebase, not least because it was jury-rigged
         | together with no architect or style guide.
         | 
         | Also, in general, the more common the exposure, the harder it
         | is to find a link; try finding a control group of people who
         | have never been exposed to PTFEs, or HSV, and who also aren't
         | like hunter gatherers.
        
           | inciampati wrote:
           | The problem is simply observational. We don't even have
           | reliable DNA and RNA sequencing of our own bodies. And we
           | cannot reliably observe things in a host without knowing, to
           | some extent, what we're looking for first. Even that space is
           | so large, it's very hard to ascertain accurately. Biology is
           | always suffering for lack of clear observations.
           | 
           | Also, adding complexity is the difficulty or even literal
           | impossibility of observing the direct interactions of
           | elements of the system, which operate at a quantum scale,
           | that you would disturb and do disturb when attempting to
           | observe.
        
           | senkora wrote:
           | My favorite way of describing biology comes from another HN
           | comment:
           | 
           | > It's more like a _vibrating causal cloud_ than a chain of
           | causality.
           | 
           | https://news.ycombinator.com/item?id=38898335
        
       | acallaha wrote:
       | > A group of researchers mostly based at Columbia University are
       | testing whether valacyclovir, an antiviral used against HSV1, can
       | slow down cognitive decline in people with early stage
       | Alzheimer's. Between 2018 and 2024, the researchers recruited 120
       | patients and treated half with the antiviral.
       | 
       | Outsider view: while I'm excited we're making progress, I can't
       | shake a feeling of sadness that the best we could manage was a
       | study this small, started 7 years ago. If it's as pivotal as the
       | article suggests, one would hope we could get more than 60 people
       | in the experimental arm (IIUC this antiviral is widely
       | prescribed, well-tolerated, and off-patent). Nonetheless, excited
       | to see the outcome
        
         | epidemiology wrote:
         | >If it's as pivotal as the article suggests
         | 
         | Let's be honest, this is a longshot.
        
         | tim333 wrote:
         | Quite an interesting attempt to advance the general process is
         | DeepMind's project to make a cell simulation so you can try
         | chucking in drugs into the simulation and see what they would
         | do quicker than in the lab/patients. They are talking about
         | having a simple cell up in five years. Hassabis talking about
         | it: https://youtu.be/CEOOMYxMvY4
        
         | bkfunk wrote:
         | > off-patent
         | 
         | Well there's your problem: no one can make money off of it,
         | unless they develop a new delivery mechanism, etc.
         | 
         | Patents encourage developing new medicines, but not developing
         | new knowledge about (never mind use of) old medicine.
         | 
         | The solution (in the US) is obvious: federal funding of
         | research that stands to help lots of people but not make lots
         | of money. Since most of these patients (in the US) are going to
         | be on Medicare, there could be huge potential cost savings to
         | the taxpayer: memory care is EXPENSIVE, so even the paltry
         | amount covered by Medicare racks up (and the opportunity costs
         | of people paying for private memory care is enormous).
         | 
         | But instead of increasing funding for this kind of life- AND
         | MONEY-saving research, this administration is freezing and
         | slashing research funding, and specifically targeting Columbia
         | for political/Trump's-petty-grudge reasons.
        
           | absolutelastone wrote:
           | I suspect the lucrative patent system has helped create
           | rather exorbitant costs and restrictions for performing
           | trials, which hinders non-patentable research, ironically.
           | 
           | But both the federal and state govts do fund tons of such
           | research. Some states have specific Alzheimer's trials and
           | funds. I would think they could handle dirt-cheap therapies
           | like this without getting into sweeping political changes.
           | Though I suspect the solution is much harder than just run a
           | trial with the drugs we have, or else we would already be
           | hearing about mountains of evidence from doctors using the
           | medications off-label.
        
           | alzamos wrote:
           | Worth mentioning that the evidence says that patents don't
           | have an effect on new drug creation/inventions. Evidence is
           | collected here http://www.dklevine.com/general/intellectual/a
           | gainstfinal.ht..., pretty neat to know that Italy/Switzerland
           | had a patentless pharma industry until quite recently.
           | 
           | Having said that, I think you're right that under this
           | system, research/capital definitely gets directed in a
           | different way.
        
             | cyberax wrote:
             | This is bullshit. Drug research costs money, A LOT OF
             | MONEY. A new drug right now costs somewhere around $5
             | billion, mostly because 90% of drugs fail in trials.
             | 
             | mRNA vaccines, semaglutide, mAB therapies, none of these
             | would have happened without patents as an incentive.
        
           | bookofjoe wrote:
           | >Well there's your problem: no one can make money off of it,
           | unless they develop a new delivery mechanism, etc.
           | 
           | You hit the nail on the head. Ketamine is a generic drug that
           | costs next to nothing; Spravoto (ketamine-derived nasal
           | spray) is already a billion dollar/year drug for Johnson &
           | Johnson, with prospects of $5 billion/year.
           | 
           | Source: https://archive.ph/rzqxt [Wall Street Journal]
        
           | cyberax wrote:
           | > Well there's your problem: no one can make money off of it
           | 
           | You can patent new applications of an existing drug. This has
           | been somewhat of a problem, as companies can just look at how
           | drugs are being used off-label, and patent some of these
           | uses.
        
         | absolutelastone wrote:
         | This article is all the supporting evidence without any of the
         | setbacks and failures at reproducing the correlations. There
         | have been attempts at showing benefits with antivirals before.
         | Just not a full-on double-blind study apparently. I recall
         | reading about a study with high doses that showed no benefit
         | for people in early stages.
         | 
         | The 7 years time duration probably comes from the size of the
         | study and also how long it is believed to take to get benefit
         | if there is one. I would think if it really worked they would
         | have stopped early for ethics reasons because they should also
         | give the treatment to the placebo arm rather than watch them
         | decline while knowing how to prevent it.
        
       | vjk800 wrote:
       | I don't know what it looks like from the perspective of someone
       | in the field, but just as someone who is interested in this sort
       | of stuff, it seems more and more plausible that quite many of
       | diseases that have grown more prevalent in the last century,
       | especially autoimmune diseases, are cause by viruses.
       | 
       | It makes sense: the viral pressure has increase by a lot due to
       | both increase in population density and increased travel across
       | the world. At the same time there has been an increase in many
       | autoimmune diseases, many types of cancer, Alzheimer's disease,
       | etc. Also, from some proven cases, we know that viruses can
       | trigger serious diseases (MS disease, type 1 diabetes).
        
         | bloqs wrote:
         | Immunocompromisation due to chronic inflammation from dietary
         | issues and stress in addition to the above as well
        
           | anovikov wrote:
           | The frequently cited "stress" thing of modern lives is just
           | eyebrows-raising. Do anyone actually believe that lives of
           | people 100 or 200 years ago have been less stressful?
        
             | giantg2 wrote:
             | It's possible they had better support systems due to larger
             | families, church being more prominent, etc.
        
               | MrMcCall wrote:
               | Any form of positive community is helpful, religous or
               | not. Just having caring neighbors is a boon to well-
               | being.
        
             | theoreticalmal wrote:
             | I think the idea is that the cells are stressed due to
             | inflammation due to diet, rather than psychological
             | feelings of stress
        
               | anovikov wrote:
               | Average "healthy" body temperature is down more than half
               | degree exactly because of reduction in inflammation.
               | People used to have very unsanitary lives and were
               | fighting infections nonstop. 37.0C was the "normal" body
               | temperature when the "norm" was first discovered in the
               | early XIX century, now it's considered to be a sickness
               | already.
        
               | xeromal wrote:
               | I'm not an expert but maybe keeping the immuno-army busy
               | with constant infections keeps it from going bored and
               | attacking itself
        
               | serf wrote:
               | also not-an-expert opinion, but an average higher body
               | temperature would reduce immune system workload by virtue
               | of killing a lot of stuff dead via inhospitable
               | environment before an immune reaction could ever muster..
        
             | phkahler wrote:
             | Work is not the same as stress. People today (especially
             | near the bottom of the ladder) are not in control of their
             | own destiny like they used to be. It's a different kind of
             | stress.
        
               | victorbjorklund wrote:
               | Slaves were more on control of their own destinys than
               | someone working an entry job today?
        
               | anovikov wrote:
               | And they used to be more in control? Epidemics wiping out
               | whole families? Gulags, concentration camps? Religious
               | violence? Persistent threat of starvation death that was
               | just the norm of life? One year of crop failures, and
               | your kids are dead. Two years, and you are dead yourself.
               | And it doesn't depend on you at all, just bad luck (if
               | there was too much luck - like a generation without crop
               | failures - population doubled, then just one year of crop
               | failures meant you were dead). And yeah, the Church that
               | keeps telling people that they were all sinners and will
               | burn in hell, very comforting. Tell me about "control of
               | one's own destiny".
        
               | cosmic_cheese wrote:
               | I think there's something to this. Life in those times
               | was difficult and stressful, yes, but most hardships then
               | were entirely beyond any individual's control. To a large
               | extent, good times and bad times would come and go
               | regardless of what you did.
               | 
               | Contrast this to the modern day where more often than
               | not, hardships are attributed to personal failings ("You
               | should've worked harder if you didn't want to be stuck
               | working abusive under-compensated jobs!") and people
               | perpetually teeter on the edge of a knife suspended over
               | a bottomless pit. If anything goes wrong, it's treated as
               | nobody's fault but your own, regardless of the reality of
               | the situation. It's almost a type of psychological
               | torture.
        
             | vjk800 wrote:
             | Physical activity gives an outlet to stress, and people
             | used to get way more of it. Stress and physical effort are
             | supposed to go hand-in-hand; you feel stressed, which gives
             | you a boost of adrenaline, which you need to physically
             | fight back whatever caused the stress. When the physical
             | component is missing, the stress just lingers and wreaks
             | havoc on your body.
        
             | ta12653421 wrote:
             | well, you may read & discuss this one? :)
             | 
             | https://en.wikipedia.org/wiki/List_of_common_misconceptions
             | _...
        
           | theoreticalmal wrote:
           | Have you read Dr. Casey Means' book on this?
        
             | idiotsecant wrote:
             | Literally every time in the history of the universe when
             | someone has structured a sentence like this, in this
             | context, whoever they're talking about ends up being a
             | giant crackpot. I'm not saying this person is a crackpot,
             | just that the pattern recognition systems are throwing off
             | some alarms.
        
               | rubyfan wrote:
               | First sentence from wikipedia says:
               | 
               |  _Casey Means is an American functional medicine
               | /holistic medicine physician, entrepreneur and author._
               | 
               | https://en.m.wikipedia.org/wiki/Casey_Means
        
               | gcanyon wrote:
               | I'm more influenced by this passage:
               | 
               |  _Means withdrew from her medical residency at age 30.
               | She has attributed this decision to the lack of training
               | she received about nutrition and the underlying causes of
               | chronic disease. Means dedicated her practice to
               | functional medicine, which focuses on the root causes of
               | disease._
        
               | kwertyoowiyop wrote:
               | As one comedian said: "Do you know what they call
               | alternative medicine that works? Medicine!"
        
               | serf wrote:
               | that's cute but how much alternative medicine eventually
               | finds a way into real medicine?
               | 
               | in other words : someone telling someone to practice yoga
               | to relax and reduce their heart rate 200 years ago was a
               | quack right up until the point that modern doctors
               | decided to include it in their repertoire?
               | 
               | it's a cute joke but it skips over the fact that there
               | seems to be an 'alternative medicine -> real medicine'
               | pipeline, even if a lot of it turns out badly.
        
               | gcanyon wrote:
               | The actual quote (from memory, but I just listened to the
               | monologue a minute ago): "Do you know what they call
               | alternative medicine that's been scientifically proven to
               | work? Medicine!"
               | 
               | In other words, the quote is exactly referring to your
               | "pipeline."
               | 
               | Tim Minchin's "Storm" monologue:
               | https://www.youtube.com/watch?v=KtYkyB35zkk
        
               | cyberax wrote:
               | Medicine as a science didn't exist 200 years ago.
               | 
               | Breath exercises, and physical therapy for relaxation
               | were mainstream in 1960-s.
               | 
               | > it's a cute joke but it skips over the fact that there
               | seems to be an 'alternative medicine -> real medicine'
               | pipeline
               | 
               | Not really. Most of the non-medicine (I refuse to call it
               | "alternative") stays non-medicine: acupuncture,
               | homeopathy, all the "energy meridians" nonsense,
               | ayurveda, alkaline foods, etc.
               | 
               | And even with activities like yoga, it's not more
               | effective than other types of similar physical activity.
               | There is some very weak evidence that yoga _with_
               | physiotherapy might be more effective than just increased
               | levels of physiotherapy.
        
               | gcanyon wrote:
               | Tim Minchin! (about 4 minutes in):
               | https://www.youtube.com/watch?v=KtYkyB35zkk
        
               | absolutelastone wrote:
               | Well that red flag versus the immediately-preceding
               | passage listing a Doctor of Medicine degree at Stanford
               | Medical School.
               | 
               | I looked into one of the links and apparently she pushes
               | fairly mainstream preventive medicine stuff, diet,
               | exercise, and screening tests. The only questionable
               | thing I saw was the continuous glucose monitoring thing
               | which the jury may still be out on when it comes to non-
               | diabetics.
        
               | nradov wrote:
               | I haven't tried a continuous glucose monitor myself but
               | those non-diabetics who have generally claim that it gave
               | them interesting insights into how their blood glucose
               | level reacted to different foodstuffs and timing of
               | meals. There is a lot of individual variation there due
               | to genetics, lifestyle, gut microbiome, etc. We'll
               | probably never see a large-scale, long-term randomized
               | controlled trial to show that CGM use improves health
               | outcomes for non-diabetics. But for healthy people who
               | already have the basics dialed in, a CGM can probably
               | help them eke out some additional marginal gains.
        
               | basisword wrote:
               | If you end up dealing with a chronic disease that medical
               | doctors completely fail in dealing with, you naturally
               | get driven to look at "alternatives". There's a lot of
               | nonsense out there - but some of it works. As a former
               | skeptic I'm now much less dismissive of these things due
               | to my own circumstances. Particularly when I can see that
               | poor medical treatment over the years actually
               | exacerbated my condition and being less skeptical could
               | have improved my quality of life significantly sooner.
        
         | giantg2 wrote:
         | Has viral pressure really increased? It seems stuff spread
         | globally a few generations ago with things like the flu in the
         | early 1900s. Even in the middle ages you had stuff like the
         | plague.
         | 
         | What has changed is the sterility of our environment. Better
         | bathing, more hand washing, food safety rules, etc. There have
         | been theories that autoimmune diseases might be increasing
         | because we aren't exposed to enough "normal" pathogens.
         | 
         | I'm highly suspicious that higher viral pressures are the cause
         | of increasing dementia rates, as it seems we're exposed to less
         | today.
        
           | Nux wrote:
           | Agreed. We've had this immune system battling stuff non-stop
           | throughout evolution and now we're living in these clinical
           | environments and it's going haywire.
           | 
           | Not to mention we're poisoning ourselves with all sorts of
           | novel stuff, especially poor hi-carb nutrition, ultra
           | processed food and pollution from various sources that act as
           | endocrine disruptors and God knows what else.
        
           | vjk800 wrote:
           | Bacterial, fungal and parasitic load has lessened, for sure,
           | due to sterility of the environment, because many of those
           | come from exposure to animals and plants. But viral load from
           | viruses that spread from human-to-human and live exclusively
           | in humans has increased because there are more humans and
           | they spread the diseases around the world more effectively
           | than before.
           | 
           | Yes, we probably get way less pathogens overall than we used
           | to, but at the same time we get more pathogens that live
           | exclusively on humans (such as respiratory viruses).
        
             | hn_throwaway_99 wrote:
             | > But viral load from viruses that spread from human-to-
             | human and live exclusively in humans has increased because
             | there are more humans and they spread the diseases around
             | the world more effectively than before.
             | 
             | This seems like pure conjecture to me, and without any
             | actual evidence to support it, I'm disinclined to believe
             | it. My guess is that the number of people any one
             | individual interacts with has gone down considerably since
             | the beginning of the century, and earlier. Before the
             | advent of the car, shared forms of travel were much more
             | common. People do much less forms of basic shopping than
             | they used to given the rise of the Internet. Air travel,
             | while much faster, is much less crowded that the ship
             | travel of earlier generations.
        
               | inetknght wrote:
               | There are significantly more humans in which a human-
               | borne virus could live and/or mutate.
        
               | nradov wrote:
               | There are significantly fewer humans living in close
               | contact with livestock in which a zoonotic virus could be
               | transmitted. I'm skeptical that there has been a net
               | increase. It's possible but I haven't seen any reliable
               | evidence one way or the other.
        
               | inetknght wrote:
               | But there are significantly more amounts of livestock in
               | contact with those fewer humans.
               | 
               | Think of it this way: more total numbers = more
               | opportunities for viruses to grow or mutate = more
               | chances for runaway or novel infections. Runaway
               | infections are dealt with fairly well by government
               | entities. Novel infections... might be harder to discover
               | because they're, well, novel.
        
               | Al-Khwarizmi wrote:
               | > Before the advent of the car, shared forms of travel
               | were much more common. Air travel, while much faster, is
               | much less crowded that the ship travel of earlier
               | generations.
               | 
               | Maybe in the US. Definitely not in most of the world. For
               | my grandparent 70 years or so ago, the way to travel long
               | distances was riding a donkey. Now travel by bus, train,
               | subway, etc. is really common and something that most
               | people experience often. 100 years ago of course there
               | were trains, stagecoaches, boats, etc. but they were for
               | a tiny minority of society or for special occasions (like
               | to migrate a different continent to not return in
               | decades, etc.). I'm also pretty sure air travel has a
               | much higher penetration than ship travel would have 100
               | years ago.
               | 
               | As further anec-data points, there are much more massive
               | gatherings now (concerts, sports, etc. - church used to
               | be the major gathering, but churches tend to be ample and
               | ventilated). And every parent knows that daycare and
               | kindergarten are a major vector for pathogens. I used to
               | get like a cold a year with 2 days mild congestion, and
               | since my kid started kindergarten (he didn't go to
               | daycare) we all started getting sick like monthly or so,
               | for a couple of years. Putting dozens of kids in a closed
               | space for hours is something that just wasn't a thing in
               | previous generations either.
               | 
               | So personally, yes, I would bet that chances for pathogen
               | spread have increased greatly.
        
           | crowselect wrote:
           | Time scale. Viral load has increased dramatically over what
           | it was like 1000 years ago. The change over the past 100
           | years is all lifespan due to antibiotics and the sterility
           | another comment is pointing the finger at. It's possible that
           | viral load + lifespan = cancer, dementia, autoimmune stuff,
           | etc.
        
         | strawpoll-foe wrote:
         | I have both T1D and MS. For MS, one leading idea is that
         | getting exposed to Mono later in life can trigger the disease.
         | There's solid evidence for this.
         | 
         | For T1D, it's similar - there's a notion that you're
         | genetically predisposed to it and certain types of infections
         | during adolescence can cause it to manifest.
         | 
         | I've had discussions with researchers in the space and
         | apparently certain autoimmune diseases happen less often in
         | "grubbier" parts of the world (their words, not mine) even when
         | the population density is high, and an inference here is that
         | >early exposure< to certain infections might not trigger some
         | of these problematic autoimmune reactions.
         | 
         | Side note: these diseases aren't fun, especially when working
         | in tech. I'm appreciative of those dedicating their lives to
         | researching autoimmune disease.
        
           | delusional wrote:
           | > I've had discussions with researchers in the space and
           | apparently certain autoimmune diseases happen less often in
           | "grubbier" parts of the world
           | 
           | Is that corrected for mortality? It seems like an analysis
           | like that would be quite prone to survivor bias.
        
           | sigmoid10 wrote:
           | For MS in particular there's several EBV mRNA vaccines in
           | clinical trials - not just to prevent mono itself, but also
           | to prevent long term complications (theoretically including
           | MS) for people who already had it.
        
         | pretzellogician wrote:
         | And obesity.. there are several adenoviruses associated with
         | it. Example: https://www.nature.com/articles/s41366-021-00805-6
         | 
         | (Although the article takes pains to say that obesity is
         | multifactorial, conflicting evidence in humans, etc.)
        
         | kwertyoowiyop wrote:
         | Can we take it as proven that the rate of these diseases has
         | increased? I wonder if in the past some conditions we now
         | classify as particular diseases were considered a normal part
         | of aging, perhaps at most getting a blanket classification of
         | "senility".
        
         | Melatonic wrote:
         | Bacterial infections can also trigger autoimmune diseases -
         | it's not just viruses.
         | 
         | Realistically immune systems are extremely complex and I
         | suspect there are probably lots of environmental triggers
         | beyond viruses and bacteria as well
        
         | Mo3 wrote:
         | My girlfriend has Crohn's disease that can be directly
         | correlated to food poisoning while on vacation. Now years later
         | I can't even count the times I've read and heard exactly the
         | same story from other people with Crohn's disease. A simple
         | search for "Crohn's food poisoning" turns up hundreds of
         | results. I can't believe this is not being investigated with
         | higher priority
        
       | tim333 wrote:
       | Along similar lines there was a good article in the Guardian: The
       | brain microbiome: could understanding it help prevent dementia?
       | https://www.theguardian.com/lifeandstyle/2024/dec/01/the-bra...
       | 
       | Apparently viruses and also bacteria and fungi getting in the
       | brain and causing problems are quite common.
        
       | paul_h wrote:
       | "Alzheimers-like" is a thing too:
       | https://www.research.uky.edu/news/uk-researchers-find-alzhei...
       | (after covid). I am sure there were other studies, but I'm darned
       | if I can find them after searching just now.
        
       | zhivota wrote:
       | I think there is something to viruses being a big agent of aging.
       | I'm 40 and recently came down with a bad case of norovirus,
       | followed by some kind of flu-like thing. 3 weeks of illness.
       | Afterwards, I felt as if I had aged 10 years, and looking into
       | the mirror it was like looking at what I will probably look like
       | at 50.
       | 
       | It made me wonder how much of aging is mediated by damage from
       | infection, which we fight off, but come out of weaker for it.
       | 
       | It certainly makes me want to double check all my vaccines, and
       | once my kids are older, practice a little better hygiene
       | including things like masking up in tight spaces (pretty much
       | impossible with a 6 and 9 year old in the house, they are the
       | vector right now).
        
         | chneu wrote:
         | Getting sick is a very stressful period, physically and
         | mentally. It absolutely ages you.
         | 
         | We're sick far less often nowadays. Common illnesses were more
         | common in previous generations. Back in the day "everyone got
         | measles".
         | 
         | While people fear being "too clean" there is also a downside to
         | being "too exposed".
        
         | AnotherGoodName wrote:
         | One that i recently experienced is 'reactive athritis' which is
         | a form of athritis commonly experienced after a stomach virus.
         | 
         | If you start looking into it it's due to an immune response
         | that occurs in people with the
         | https://en.wikipedia.org/wiki/HLA-B27 gene and that gene is
         | associated with a large number of athritis risk factors (but
         | also resistance to a lot of things including HIV).
        
           | gambiting wrote:
           | I've had the same. It took over 5 years for me to go back to
           | normal. Apparently somewhat common, but rarely talked about.
           | And any virus can cause it.
        
       | smeeger wrote:
       | the debunked theory that certain diseases like alzheimer's and
       | autism are caused by viruses cannot be true because that would
       | mean that they are caused by inflammatory insult and that would
       | mean that vaccines contribute to or cause certain diseases. this
       | is dangerous thinking and should not have a platform anywhere
        
         | Mordisquitos wrote:
         | > _the debunked theory that certain diseases like alzheimer 's
         | and autism are caused by viruses_
         | 
         | No. Not only is it not "debunked", it is not even "a theory".
         | 
         | > _cannot be true because that would mean that they are caused
         | by inflammatory insult_
         | 
         | No. Something being caused by a virus does not imply that the
         | mechanism is "inflammatory insult".
         | 
         | > _and that would mean that vaccines contribute to or cause
         | certain diseases_
         | 
         | No. That certain viral infections may cause ill effects by
         | means of inflammatory processes does not imply that "vaccines
         | contribute to or cause certain diseases".
        
       | SubiculumCode wrote:
       | and 20ish percent of autism. See maternal immune over-activation.
        
       | torcete wrote:
       | Wouldn't this theory be easy to prove by sequencing brain tissue
       | samples from deceased patients?
       | 
       | Probably more than 90% of the reads would be human, but still.
        
       | MPSFounder wrote:
       | Can someone explain to me how it can be so hard to track down the
       | exact cause for this disease? My grandma passed from it. It seems
       | to be relatively common. What makes this so difficult to treat
       | relative to other diseases? Freshman year of college I was told
       | it was amyloid proteins. Then make a drug to eliminate them. I am
       | having difficulty seeing how 20 years since my grandmother
       | passed, the cause still shows as unknown on reputable sources.
        
         | pedalpete wrote:
         | We still don't have a correct model for what Alzheimer's is,
         | and therefore how to treat it.
         | 
         | Compare this to something like HIV, where we were able to
         | quickly understand that the virus attacks CD4 cells, and limits
         | the body's ability to defend from disease.
         | 
         | With Alzheimer's, we're still in the - is it amyloid and tau?
         | is it inflammation? is it viral?
         | 
         | This is compounded by our limited understanding of the brain.
         | 
         | Another hypothesis which I ascribe to is that we are lumping
         | multiple diseases under the label of Alzheimer's because we
         | don't understand it enough.
        
       | narrator wrote:
       | This is why methylene blue has been so successful in Alzheimer's
       | research. It's antimicrobial and gets into the brain easily.
        
         | ProjectArcturis wrote:
         | By "so successful", do you mean "failed all pivotal clinical
         | trials"?
        
       | pedalpete wrote:
       | We cannot ignore that we know so little about how Alzheimer's
       | works, we are potentially lumping multiple diseases under the
       | same label.
       | 
       | The amyloid hypothesis doesn't have to be wrong for the T3D to be
       | true, and the viral potential to also be true if we are looking
       | at 3-5 different diseases that have similar presentations. This
       | also somewhat suggests why it may be the most common form of
       | dementia.
       | 
       | I work in the neurotech/sleeptech space
       | (https://affectablesleep.com) and there is a strong link between
       | sleep quality and Alzheimer's. It is theorized that AD is more
       | common in women due to the lack of sleep through child-rearing
       | and menopause, which decreases the brain's ability to remove
       | amyliod/tau. Of course, this is only relevant to the amyliod
       | hypothesis.
        
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