Didn't see any mention of this so I thought I'd throw it out for your consideration:

You may want to try having your wife wear a good dust mask over her mouth and nose to filter the air she is breathing. If the headaches disappear or diminish significantly, then at least you will have good idea that the problem is air-borne (like mold) and you will have a better idea of what may be going on. Also, as weird as it may look, at least if you and your wife need to go somewhere in that car, you will have a way to do it (if it works).

In the absence of air-borne problems, your wife may be very sensitive to and be reacting to a very high frequency or very low frequency sound coming from somewhere that is causing her headaches (my wife is an audiologist and suggested that idea). Women, especially, are sensitive to and can hear very high frequencies that men cannot hear, especially as men age. Sounds like that may be originating from some metal part wearing out (break shoes, bearings, etc.) or even a window that isn't closing all the way, causing some road noise.

Best of luck.

Gary