Quoting his article:

I would bet on the following: A therapy whose sole intended mechanism involves amyloid production or clearance, in a randomized, double-blind, placebo-controlled trial, will, in the next 12 years, achieve a slowdown of cognitive decline of at least 75%, with a p-value below 0.001, in its preregistered primary cognitive endpoint (or an average of all such endpoints if more than one exists). I’d eventually expect better than 75% efficacy, but getting stuff to work takes time, and I wanted to make a prediction which can be tested in a reasonable timeframe.

On the other hand, if a clinical trial completes earlier than 12 years from now (perhaps [73], reading out in 2027), sustains extremely good amyloid clearance at the preclinical stage, and has a good safety profile, but doesn’t make substantial progress towards this 75% goal, then I would consider this prediction refuted in advance.

Resolves yes if the first condition occurs by the end of the market

https://www.astralcodexten.com/p/in-defense-of-the-amyloid-hypothesis

• Update 2025-08-18 (PST) (AI summary of creator comment): - No early resolution: The creator intends to wait until the end of the 12-year window (market close) to resolve.

  • "Refuted in advance" clause: Will not be used for early NO; interim successes also won't trigger early YES.