Do viruses trigger Alzheimer's?

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.

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.).

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.

Memantine is an NMDA antagonist like ketamine and other dissociatives.

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).

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".

Important to take certain antioxidants and supplements after. Plus whole good food. Focusing heavily on good sleep and rest (so hard). And doing some level of exercise, but even just starting with walking.

I had a post viral effect after Covid. But maybe 2 months. Then I finally took it easy with working out and it went away.

> 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.

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

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.

>If it's as pivotal as the article suggests

Let's be honest, this is a longshot.

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.

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.

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

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”.

Immunocompromisation due to chronic inflammation from dietary issues and stress in addition to the above as well

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.)

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

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.

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.

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?

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

We don't need them but I don't see a problem either if they are appropriate to the article as in this case.

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.

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.

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.

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...

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.

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.

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.