Alzheimer's disease and anaesthesia: implications for the central cholinergic system

Alzheimer's disease (AD) is associated with a loss of cholinergic neurons resulting in profound memory disturbances and irreversible impairment of cognitive function. The central cholinergic system is involved in the action of general anaesthetic agents. Anaesthetic modulation of cholinergic transmission has profound effects on brain function via a cascade of synaptic and postsynaptic events by binding both nicotinic and muscarinic receptors. During general anaesthesia, decrease in acetylcholine release and depression of cholinergic transmission facilitates the desirable effects of general anaesthetics, such as loss of consciousness, pain, voluntary movements and memory. From this point of view, patients with AD, characterized by a compromised neuronal transmission, represent particular cases in which the choice of anaesthesia drugs may have a negative effect on the postoperative outcome. A future challenge may be the identification of brain targets of general anaesthetics which do not expose patients to postoperative cognitive dysfunction, nor interfere with prognosis of brain degenerative disease.