The word used in the Amendment is “unable” to perform the duties... The President merely needs to stand before the citizenry and declare “I am able and willing to perform my duties” and that pretty much settles it...
There was a decent episode of West Wing about the 25th. Martin Sheen’s daughter was kidnapped by terrorists and his CoS told him that fact made it impossible to serve as POTUS . He sent the unable to serve message and as there was no VP, the Speaker, a Republican played by John Goodman, became acting POTUS.