If you turn on that option first, then browse for the program, it becomes the new default.
You shouldn't lose any settings, but it's a good idea to make a config backup first, just to be sure. You can use Settings > Backup & Restore to do that.
When you install a new version (e.g. Opus 11 to Opus 12), you'll be switched to the new default toolbars by default (since they have some new commands which weren't in the old version), but you can turn your old toolbars back on in a few clicks if you want to go back to them. More detail on what do to here: Your old toolbars are still there after you upgrade
Font sizes also get reset when installing Opus 12 for the first time (due to the new DPI scaling support).
Other than that, pretty much all settings should be preserved, as long as you install the new version over the top of the old one. (If you uninstall, it wipes the config, but there's no need to uninstall the old version.)