re: Why is Appalachia so poor and decrepit

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It kind of is though, it's walking textbook example of Dutch Disease (Louisiana is as well).

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you’re right.

What I was really trying to say is the population there now does not allow for economic development, due to the brain drain. I can’t see Appalachia ever being revitalized

Is Appalachia that much worse than poor states like Louisiana or Mississippi?

You used to be able to pick up some cheap acreage there compared to elsewhere. And that is comparing to NEOhio rust belt prices. But not so much anymore. And last time I searched around, it was a decade ago.
So, I can only imagine the prices now.
I blame Virginia.

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De-industrialization, war on coal,and the proliferation of drug addiction

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That pretty much sums it up. There are thousands of small towns across Appalachia, and the rest of the country for that matter, who relied on some sort of local industry to keep them afloat. It could be the local sewing plant, coal mine, saw mill, etc that literally were the beating heart of the town. Those all left and went to places like China Vietnam, Mexico, etc. and left a dying corpse of a town behind.

The town I grew up close to is a prime example of this. In the 70s & 80s, Altoona, AL was a small but thriving little town. It had started out as a coal mining town in the late 19th century. But the mines gave out after WWII. Textiles moved in though. They had a factory that made Liberty overalls. It was the main employer of the town for decades. It closed up in the 90s and production was moved to China. Now it’s just depressing to drive though and see what it is now compared to 40 years ago. There’s almost nothing left.