5 ms·

Is this correlation or causation? The problem with past approaches appears to be a focus on states that are probably just correlates.

deleted 4y ago
[deleted]
xen2xen1 4y ago
If you run out of correlations, eventually one has to be a causation!
- dogma1138 4y ago
  No you don’t, in fact there is absolutely no reason why Alzheimer’s has to have a single cause you can have multiple genetic, environmental and pathogenic factors leading to the condition which eventually exhibits itself as Alzheimer’s.
moloch-hai 4y ago
This is the important insight. Beta amyloids, tau tangles, now angry immune cells. Maybe look into infections that provoke them all? What we know is that certain vaccinations (Tdap, flu) predict a 40% reduced risk of dementia, and recent treatment with valacyclovir, a herpes treatment, similarly. And autopsies of Alzheimer's patients show brain infections. What will all the amyloid biochemists do when that whole line of research is abandoned?
- D-Coder 4y ago
  WOW, I hadn't seen that about vaccinations. Seems to be a good deal of info from around 2020 about this. One example is https://aaic.alz.org/releases_2020/vaccines-dementia-risk.asp https://aaic.alz.org/releases_2020/vaccines-dementia-risk.as....
  - richardatlarge 4y ago
    Unfortunately, again, the vaccines were not applied to a single population as a variable, so there’s no evidence I don’t think to see a causal link: those who seek out such shots are a somewhat unique population
    - lost_tourist 4y ago
      I'm lost, people who seek out flu vaccines are a unique population?
    - moloch-hai 4y ago
      This is an example of the old trope that only random controlled trials (RCTs) can demonstrate causation. It was doctrine enforced until the '90s. Nowadays, statisticians have protocols to extract a causation signal from population studies that are large enough. That is not to claim lack of vaccination causes dementia. But it means something affected by vaccination does. When you follow a cohort of 46,000 patients for six years, you get enough good data to draw strong conclusions. That the same numbers came out for a disjoint population of 12,000, over the same period, demonstrates it. But statistics only points you in a direction, it is not biochemistry.
- Py-o7 4y ago
  My understanding of one guess around e.g. annual flu shots is not so much protection from infection as frequent stimulation of the immune system being beneficial in particular for Apoe4 carriers. E.g. from p. 329 of Lieberman's Exercised: > Although Westerners who carry the two copies of a gene called Apoe4 (a protein that transports fats in the bloodstream) are three to fifteen times more likely to get Alzheimer's in old age, elderly Tsimane with the same ApoE4 gene are less likely to show declines in cognitive performance if they suffer from many infections. ------ I have heard something similar about ApoE4 carriers in Nigeria though don't have a source on hand. Basically a lot of variations of the hygiene hypothesis and possibly compatible with "angry immune cells". Definitely not a "mystery solved" though.

deleted 4y ago

[deleted]

xen2xen1 4y ago

If you run out of correlations, eventually one has to be a causation!

dogma1138 4y ago
No you don’t, in fact there is absolutely no reason why Alzheimer’s has to have a single cause you can have multiple genetic, environmental and pathogenic factors leading to the condition which eventually exhibits itself as Alzheimer’s.

moloch-hai 4y ago

This is the important insight. Beta amyloids, tau tangles, now angry immune cells. Maybe look into infections that provoke them all? What we know is that certain vaccinations (Tdap, flu) predict a 40% reduced risk of dementia, and recent treatment with valacyclovir, a herpes treatment, similarly. And autopsies of Alzheimer's patients show brain infections. What will all the amyloid biochemists do when that whole line of research is abandoned?

D-Coder 4y ago
WOW, I hadn't seen that about vaccinations. Seems to be a good deal of info from around 2020 about this. One example is https://aaic.alz.org/releases_2020/vaccines-dementia-risk.asp https://aaic.alz.org/releases_2020/vaccines-dementia-risk.as....
- richardatlarge 4y ago
  Unfortunately, again, the vaccines were not applied to a single population as a variable, so there’s no evidence I don’t think to see a causal link: those who seek out such shots are a somewhat unique population
  - lost_tourist 4y ago
    I'm lost, people who seek out flu vaccines are a unique population?
  - moloch-hai 4y ago
    This is an example of the old trope that only random controlled trials (RCTs) can demonstrate causation. It was doctrine enforced until the '90s. Nowadays, statisticians have protocols to extract a causation signal from population studies that are large enough. That is not to claim lack of vaccination causes dementia. But it means something affected by vaccination does. When you follow a cohort of 46,000 patients for six years, you get enough good data to draw strong conclusions. That the same numbers came out for a disjoint population of 12,000, over the same period, demonstrates it. But statistics only points you in a direction, it is not biochemistry.
Py-o7 4y ago
My understanding of one guess around e.g. annual flu shots is not so much protection from infection as frequent stimulation of the immune system being beneficial in particular for Apoe4 carriers. E.g. from p. 329 of Lieberman's Exercised: > Although Westerners who carry the two copies of a gene called Apoe4 (a protein that transports fats in the bloodstream) are three to fifteen times more likely to get Alzheimer's in old age, elderly Tsimane with the same ApoE4 gene are less likely to show declines in cognitive performance if they suffer from many infections. ------ I have heard something similar about ApoE4 carriers in Nigeria though don't have a source on hand. Basically a lot of variations of the hygiene hypothesis and possibly compatible with "angry immune cells". Definitely not a "mystery solved" though.