I had to do some accessibility QA for a large shrink-wrapped software application, and it's quite the ordeal. I liken it to trying to operate an application through a telephone interface. When you're digging through menus, you need to listen to every. single. menu. entry. before deciding which one you want, and I found it far too easy to get distracted and forget where I was.

I suppose users who are used to dealing with accessibility software are used to this kind of interface, but I think it requires a level of patience that sighted users are not accustomed to (at least when dealing with their desktop software).