Firstly, thanks very much for sharing your thoughts on this topic, johnt.

"The Braak hypothesis says that PD starts in the gut, before spreading to the brain. It is reasonable therefore to suggest that the dopaminergic neuron loss is higher in the gut than in the brain, ...".

I may be wrong, but my understanding is that it doesn't work that way. My understanding is that the dopaminergic neurons in the substantia nigra produce dopamine, and that dopamine is used in the striatum, for control of muscles. Whether those muscles include the muscles associated with the GI tract, and if not, where the GI-tract muscles are controlled from, I'm not sure.

Also, it is my understanding that the neurons of the Enteric Nervous System (ENS) can tolerate the presence of alpha-synuclein aggregates. It is the dopaminergic neurons of the substantia nigra (and the cholinergic neurons of the locus coeruleus) which can not.

However, the hypothesis that medicating during the night might improve non-motor symptoms such as constipation, is worthy of investigation (IMHO).