How large are your collections? In my experience, it is no good having them larger than a few hundred per, at least on a Kindle. Takes too long to add/remove/sync them (about a minute to add or remove), and it has nothing to do with how much is on the device. No such problems with the mobile apps.
Fortunately my two largest collections were rendered moot by the Read/Unread flag (since that is what I was using those large collections for). The remainder are all <100 items and no issues with those.
I cannot advise about the effects of having that many books on device other than it is going to take awhile to generate search index and while it is doing that you might as well forget about doing anything else with the device. Patience is required.
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