I don't get any actual FPS drop, per se, but there is a noticeable slowdown in the game (as it how long it takes for a day to tick..probably goes from 0.5s per day at the start to 1-2s per day by year 100) as it progresses, but not enough to make it unplayable by any means. However, I expect a certain slow down because as Empires grow, POP's do POP stuff etc, there's more going on. And this is a galaxy of 5k stars with 2x habitable worlds.
Oh and I must run about 60 mods all in all, some cosmetic, but others huge overhauls like Alphamod.