The Galactic Empire has fallen. Wait it got back up. No it's definitely down and not getting up. Did it suddenly get dark in here?
Galactic Empires, human alien or mixed are a staple of SF. They rise over centuries and they fall. After they fall there's usually a period of anarchy, chaos, and conflict with loss of technology. Typically it is many decades or centuries before anyone notices anything is wrong and the fall is inevitable.
I call fiat. I love the idea of the empire falling. I think it's written into the DNA of my generation by Asimov, Niven, Pournelle, and many others (thanks Atomic Rockets website.) I just think the particulars could be changed to make things interesting.
First why do you need an ancient galaxy spanning empire? We're too close to blowing ourselves up now. There's no reason that will change in the next few centuries. A galactic empire is also -galactic! You're telling me that nowhere, no place, no planet is immune to the chaos and destruction? Asimov covered it better than I could. But a society collapse after humans have settled a relatively small bubble of space is a little more believable. Twenty or so worlds dragged into a war or having it spill over onto neutral parties is more believable than thousands of worlds where no one can carve an island of stability.
You don't need centuries for a society to fall, though it does make for epic novels. Greg Christopher covered this in his game: Cascade Failure (free on RPGNow.) In that setting one technological disaster triggers a chain of similar failures that causes settled space to get trashed pretty quickly. GDW of course had its Third Imperium unravel following the assassination of the Emperor and his family triggering a successor crisis and everyone to fight over crap they swore vengeance for centuries ago. Note that this is also way more possible with 20 or so worlds than a whole galaxy.
That's only one sort of disaster that could wreck the settled worlds. Plague, economic collapse (what happens to the transport industry when every one is switching to anti-grav? What about petroleum stocks when fusion becomes really cheap?) Maybe too much ftl travel causes space time anomalies in star systems (whatever those are) or the robots rise against us (they're unionizing and they have robo-lawyers!)
So we could have a societal collapse relatively soon after colonizing space. About the time where there's a high volume of interaction between the new colonies and Earth. Of course anything that happens to Earth will be a disaster for colonies that are not self-sufficient. Oh you aren't set up to build power cells? You imported them from Priam 7? Not any more.
A final thought: avoidance. In the Foundation Trilogy the collapse was inevitable and several people were aware of it. But in the case of a quicker and more immediate collapse maybe it can be delayed or averted? Perhaps a group of scholars or a government think tank is crunching the numbers and working behind the scenes to stop the new dark ages and they need a group of PCs to do the field work. They have to work behind the scenes because knowledge of the collapse could actually bring it about quicker and harder than blissful ignorance. That sounds like a campaign to me.