Have you tried on a different computer?
Doesn't seem like memory issue, collision checks are low.
Any physics or loops?
It could be some sort of CPU throttling from the OS, but that is unlikely.
Total system memory use? Caching vram to page file could cause the symptoms you describe.
Otherwise... do you have a lot of layered/invisible sprites? With a high resolution screen like that, you might overwhelm the fill rate limit of your gpu.