Supporting this idea, we previously observed that even patients with mild cognitive impairment (MCI) due to AD may benefit from cholinergic stimulation, but the treatment response depended on the degree of cholinergic impairment.5 Interestingly, even in this relatively homogenous group, the cortical levels of acetylcholinesterase (AChE), a critical enzyme of cholinergic neurotransmission, varied substantially between patients.6 There is also evidence for more severe cholinergic impairment in patients with early-onset than late-onset AD.6, –8. The gene discussed is ACHE; the disease is Cognitive impairment.