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Unpopular opinion but if you're interested in the effects of a medical product, it's 'RCT or bust' for me. I can see the case for observational analyses when randomization isn't possible, ethical, or the condition is too rare or some other such thing, but there's no such excuse here.

Conflicts of interest notwithstanding: I think you’re underestimating the difficulty of trial enrollment and follow up for such long term outcomes in the absence of an animal model or clearly defined mechanism of action

Would you expect it to be harder than for other Alzheimer's trials? I'm not sure it would be, given shingles vaccines have already shown efficacy and safety for another condition.

Absolutely *much* harder to power trials for prevention than for treatment

That said, the market for an effective Alzheimer's preventive is probably huge, so I'm still not convinced would be that financially risky to try to run, if someone thought it plausible (or as plausible as people seemed to believe, based on the observational data!)

(for a pharma company, not an individual or academic)