[DavidSJ]

“Amyloid is going to be — has to be — a part of the Alzheimer’s story, but it is not, cannot be a simple ‘Amyloid causes Alzheimer’s, stop the amyloid and stop the disease,'”

It's not quite that simple, and the amyloid hypothesis doesn't claim it to be. It does, however, claim that it's the upstream cause of the disease, and if you stop it early enough, you stop the disease. But once you're already experiencing symptoms, there are other problem which clearing out the amyloid alone won't stop.

What’s more, lecanemab only improved scores by 0.45 points on an 18-point scale assessing patients’ abilities to think, remember, and perform daily tasks.

As I point out in another comment, the decline (from a baseline of ~3 points worse than a perfect score) during those 18 months is only 1.66 points in the placebo group, It's therefore very misleading to say this is an 18-point scale, so a 0.45 point benefit isn't clinically meaningful. A miracle drug with 100% efficacy would only achieve a 1.66 point slowdown.

[kraussvonespy]

“But once you're already experiencing symptoms, there are other problem which clearing out the amyloid alone won't stop.”

Ok, maybe we’re just arguing different points here. I’ll grant that amyloids have something to do with all of this. I’m having a more difficult time understanding why one would suggest these drugs to a diagnosed Alzheimer’s patient at a point where it can no longer help.

Or is the long term thought that drugs like these will eventually be used a lot earlier as a prophylactic to those at high risk?

[DavidSJ]

I’m having a more difficult time understanding why one would suggest these drugs to a diagnosed Alzheimer’s patient at a point where it can no longer help.

My central claim is the the drugs help quite a lot, by slowing down the disease progression by 30%, and that it's highly misleading to say "only 0.45 points benefit on an 18 point scale", since literally 100% halting of the disease could only have achieved 1.66 points efficacy in the 18 month clinical trial.

This is like having a 100-point measure of cardiovascular health, where patients start at 90 points and are expected to worsen by 10 points per year, eventually dying after 9 years. If patients given some treatment only worsen by 7 points per year instead of 10, would you say "only 3 points benefit on a 100 point scale"?

Or is the long term thought that drugs like these will eventually be used a lot earlier as a prophylactic to those at high risk?

I do believe that they will be more (close to 100%) efficacious when used in this way, yes.