On 64bit Windows, it should handle it fine. It also depends how your code is written. If you use StartTransaction() you may have a larger memory overhead then if you use StartOpenCloseTransaction(). However, I'd guess that StartTransaction() will give you must faster results on a huge dataset like this
I am working on a 64 bit system and yes StartTransaction() consumes more memory but surely its faster and since memory is not an issue I have used StartTransaction() in my code. Set aside programming part.
Lets talk about a file which have 40000 blocks each with 35 attributes. According to you how much time will autocad take if I make some modifications to the file and hit save.
We dont have performance metrics to answer that question.
If you can share a buildable sample project / drawing to repdroduce the behavior, we may be able to suggest improvements that might help.