Important context is that all interventions that have assumed amyloid to be causal for Alzheimer's have failed to show material clinical improvement.

So the bar is really much higher than "did remove plaque" and the prior should be this wasn't going to improve clinical response. The fact that it didn't and was still approved is a complete abdication of what the FDA preaches. It's rare to see a uniform response from those that report on drug dev. but it has been unequivocal - the FDA needs to get its shit together.

I, personally, have little hope for that.

AFAIK there is no reliable non-invasive procedure to determine the amount of plaques in the brain. So it will be difficult to make hard statements about the effect of potential drugs on the plaques.

Also we are not really very interested in the effect on plaques, we are interested in things like cognitive behavior which are a lot easier to measure.

> Or is it more that noticing plaque reduction is fast while noticing outcome improvements would take a while?

This statement is true, but the trial will have gone on long enough to note whether or not both plaque reduction and outcome improvements happen, because plaque reduction isn't considered sufficient evidence for outcome improvement, despite some attempts to force the FDA otherwise. (Although I guess the FDA has kind of caved in at this point, given that it's conditionally approving this on the basis of plaque reduction despite seeing no outcome improvement.)

I am no expert, but my understanding (referenced obliquely in the article) is that this is not the first drug to target reducing the amyloid beta plaque, that does not show positive results. This is raising the question of whether it's treating a side-effect of the disease, rather than actually treating the disease. In other words, it's not all that surprising anymore that a drug targeting the plaque, does not work well.