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Comment by brandonb | Hacker News Reader

Agreed that we can't do as much as we'd like. There are some general health things that are believed to prevent cognitive decline, such as managing cholesterol, HbA1c, blood pressure, sleep apnea, etc. One phrase I've heard is that cholesterol at age 50 predicts cognitive health at age 70.

But hopefully we'll start to have more options and wider approvals for things like anti-amyloid drugs.

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> anti-amyloid drugs

Isn’t the viewpoint in the last decade that amyloid plaques are likely a finding rather than the underlying cause of Alzheimer’s Disease?

The "standard" theory is that amyloid leads to tau protein accumulation which leads to neurodegeneration: https://www.astralcodexten.com/p/in-defense-of-the-amyloid-h.... Which would explain why current treatments don't really work: by the time Alzheimer's has progressed to noticeable impairment there's already too much tau, so reducing amyloid will at best slow the rate of decline by reducing the formation of new tau.

> Which would explain why current treatments don't really work ... [they] at best slow the rate of decline

This is called working! I am struck by the double-standard applied to assessing treatment options for Alzheimer's vs cancers. Many (most?) Stage IV cancers are incurable, and the main goal of treatment is to slow progression of the disease. Adding years to patients' lives is absolutely worth it, assuming the side effects are not overwhelming and the costs are not prohibitive.

To wit: Moderna added ~30B to its market cap on the news that it observed _statistically significant_ improvement in its primary endpoint for treating metastatic melanoma. Great! I'm as excited about this development as anyone. A new treatment option for a terrible disease that meaningfully improves on the current standard of care (Keytruda). Sadly, Stage IV melanoma is still considered terminal, and no one suggested that Moderna changed that.

Why not reset expectations for Alzheimer's? If we manage to slow its development enough so that most patients (who tend to be elderly) would die of other causes while maintaining decent quality of life, that's a win in my book.

ever since the discovery of amyloid plaques, it's been an open question. Are they causative or a symptom? Would reducing or eliminating them help treat the disease? There is lots of data that supports amyloid as a disease treatment target, particularly in animal models. Of course the abject failure to actually develop a good anti-amyloid treatment that actually provable and significantly mitigates the disease weighs against the idea that amyloid is a good target. And the high profile frauds that have been discovered haven't helped. But, the biomedical community are not a bunch of morons. All these drug companies wouldn't have spent these billions of dollars on anti-amyloid and anti-tau if they were such obviously terrible ideas.

That's the viewpoint of everyone sensible outside of Alzheimer's research.

Those in it are still throwing billions per year at the idea.

Meanwhile, back in reality, no amyloid-beta drug has had any clinical effect in humans, other than reducing the plaques. But both the shingles and RSV vaccines are proven to reduce Alzheimer's risk.

Which did not stop the FDA from approving a useless anti-amyloid drug, leading to the resignation of several experts, one of whom called it "probably the worst drug approval decision in recent U.S. history" in his resignation letter. [0]

I can't think of a good reason why this happened.

[0] https://www.npr.org/2021/06/11/1005567149/3-experts-have-res...

not really. your comment is a vast oversimplification of a very complicated topic.

Hi there. Actually, Leqembi is a 1st gen Alzheimer’s drugs and targets amyloid plaques. But, like other responses, amyloids doesn’t seem to be hugely responsible for Alzheimers, which is why targeting things like tau proteins is being explored.

if cholesterol predicted future cognitive health we wouldn’t need dedicated tests, do we?

the better way to phrase that would be "is predictive"... there is an association, but it is not high accuracy.

The forecast predicts rain, I'm still going to look outside before I throw on a raincoat

You can do all that without an expensive blood test.

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