ACHE and Alzheimer disease: While the precise reasons for the negative outcomes of this Phase 2 trial and the Phase 3 trials with idalopirdine and intepirdine are unknown, the most parsimonious explanation is that the mechanism does not demonstrate sufficient potency as a modulator of cholinergic neurotransmission, either alone or when administered in conjunction with an acetylcholinesterase inhibitor, to yield demonstrable clinical benefit in patients with AD.