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OK, time to revisit the Donepezil and cholinergic drug question..

From Howard Hampel's facebook page:

Harald Hampel
August 2 at 8:27 PM ·
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Harald Hampel, Enrica Cavedo, Andrea Vergallo. Brain, 4 August 2018.

We agree with the suggestions of Gauthier and colleagues (Gauthier et al., 2018) for a more structured approach to therapy in Alzheimer’s disease. We also agree that there is substantial evidence towards beneficial effects of cholinesterase inhibitors for patients suffering from Alzheimer’s disease. This is why the Cholinergic System Working Group (CSWG) (Hampel et al., 2018a) concluded that ‘the weight of evidence supports the continued value of cholinergic drugs as a standard, cornerstone pharmacological approach in AD, particularly as we look ahead to future combination therapies that address symptoms as well as disease progression’.

ICM - Institut du Cerveau et de la Moelle épinière Fondation pour la Recherche sur Alzheimer Assistance Publique Hôpitaux de Paris Sorbonne Université AXA Research Fund Olivier de Ladoucette Jean-Luc Angélis Sciences et Avenir Michel-Edouard Leclerc

This is a link to the original publication of the above: https://academic.oup.com/brain/advance-article-abstract/doi/10.1093/brain/awy205/5064191

This is what Hampel was responding to:

Optimal use of cholinergic drugs in Alzheimer’s disease
Serge Gauthier Nathan Herrmann Pedro Rosa-Neto
Brain, awy204, https://doi.org/10.1093/brain/awy204
Published: 02 August 2018


Sir

We read with great interest the review article by Hampel et al. (2018) on the cholinergic system in Alzheimer’s disease. Sadly, despite the strength of the evidence towards a beneficial effect of cholinesterase inhibitors in Alzheimer’s disease, the government of France withdrew reimbursement for these medications. While we ultimately hope for a precision medicine approach to treatment as suggested by Hampel et al., there is thus still an immediate need to better define the efficacy of symptomatic drugs in Alzheimer’s disease. In fact our group demonstrated the feasibility to quantify presynaptic cholinergic depletion in vivo (Aghourian et al., 2017). We...

Issue Section: Letter to the Editor

My conclusion: Usage of 2-73 in combination with cholinesterase inhibitors is still a viable avenue of research and the combination patent is not dead.

This does not mean France's decision to stop reimbursement was a bad one, because as they are used now in SOC cholinesterase inhibitors seem to have very limited value..... but they are not completely void of value. France made a cost benefit decision - that the group of Alzheimer's patients as a whole would get more benefit from money spent on enhanced caretaking as opposed to blindly prescribing cholinesterase inhibitors.

There is a complex ethical and scientific debate here. I don't think we will have an answer until:

1) 2-73 is appproved.
2) More data on the interaction between cholinesterase inhibitors and 2-73 is collected.

IMO - this is why cholinesterase inhibitors are permitted in 2-73 trials.