When I think about your question, a couple of things come to mind;
I understand that you have practical limitations on your available time to train. But there are certain things you can anticipate and practice. Riding at night is one. Getting to your "stuff" during the ride with the least amount of hassle. Refueling quickly. Navigation. All those activities and others, when solved in advance, will ease the effort a long continuous ride takes.
At a more practical level, I start moving around on the bike and de-cramping from the time I hit 6th gear for the first time and never stop staying ahead of that condition. Have a good hydration system and use it even when you don't feel thirsty. If you would normally take a Tylenol after a long ride / take one when you start and again a few hours later. In short, stay ahead of your problems.
Lastly, as regards mental sharpness, I test frequently. I do simple math in my head. Often things like the miles to the next city and subtracting miles traveled from that last starting point. It is a solid test and because it is self administered - very hard to ignore. It also helps to consider your hours as 1/4 hour parts.
Current Rides: '14 DL1000 ADV, '06 SV650N, '93 900CBRR, '74 Ducati 750GT ['02 BMW K1200rs SOLD Aug '17]