Tacrine and other anticholinesterase drugs in dementia

It has been recognized for 20 years that Alzheimer's disease is associated with a characteristic cholinergic deficit in the brains of sufferers. Attempts with various different forms of cholinergic therapy have culminated in the licensing in several countries of tacrine, the first anticholinesterase inhibitor with Alzheimer's disease as its indication. For maximum effectiveness, tacrine needs to be used at the patient's maximum tolerated dose, up to a maximum of 160mg/day. Twenty to thirty per cent of patients respond positively to the drug but it is associated with significant side effects in one-half of all patients. The most significant of these is liver transaminase elevation, which is reversible on stopping the drug, generally asymptomatic and may not recur on rechallenge. This transaminitis necessitates intensive blood monitoring in the early stages of treatment with tacrine, or after any change in dose. A number of other anticholinesterase drugs in development give the hope of being effective without the troublesome side effects. Research is also in progress to develop methods to predict those 30% of patients who will have a positive response to the drug.