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