TL;DR - How does one create a complex User Interface in Photoshop in a way that Photoshop doesn't slow down to a crawl?

I create a lot of complex User Interface scenarios with Photoshop and routinely get to 10-20 layer comps and hundreds (thousands) of layers.

I use smart objects as much as possible; and organize, group, and label my layers meticulously so finding items is simple. However Photoshop is slowing down tremendously. Even allocating 10GB of RAM is not enough.

I hesitate flattening layer groups as I update them often as the requirements get more and more precise.

What is the best solution to this problem (so many layers that Photoshop slows down)?