Influence of cholinesterase inhibitors on cortical slow-wave activity in aging nonhuman primate

Substantial evidence has now accumulated suggesting that the cognitive decrements characteristic of Alzheimer's disease and, to a lesser degree, of normal aging, may result, at least in part, from degenerative changes in the cholinergic system innervating archi- and neocortices. This evidence for cholinergic degeneration in AD has provided the key rationale for many recent clinical trials utilizing cholinergic agents for the purpose of palliating cognitive loss. The basal forebrain cholinergic system plays an important function in electrocortical activation associated with behavioral arousal and cognitive functions. We recorded electrocortical changes from nonhuman primates following administration of potentially clinically useful cholinergic agonists as well as an antagonist. The cholinesterase inhibitors tacrine (THA) and, to a lesser extent, physostigmine (PHYSO) and amodiaquine (AMDQ), caused an upward shift in the frequency of the resting electrocortical activity, although scopolamine significantly slowed the activity below baseline levels. We believe these findings support the concept that the cholinergic system may play an important role in cognitive processes associated with cortical activation.