I use Thunderbird with two rather large IMAP accounts (one has a total of 30 000 messages across all folders) and for the last month Thunderbird has become a bit slower, not too much but still noticeable, especially when I switch folders.
In reference to an earlier SuperUser Firefox question about the location bar becoming slower over time (and which was solved with some hidden history about:config setting):
Are there any useful (hidden or not) Thunderbird settings to make it more responsive for large accounts and folders (e.g. my 'sent items' and 'archive' folder contain >10000 items)?