Effect of cholinesterase inhibitors on attention

Advantages and limits of the use of cholinesterase inhibitors (ChEI) in Alzheimer's disease (AD) are well established. Their effects result from an increase in extracellular acetylcholine (ACh) whose hydrolysis is prevented by cholinesterase inhibition. In this way, the cholinergic deficit which characterizes AD may be corrected. This overview discusses which components of the cognitive process are improved by ChEI administration. In animal experiments, the increase in ACh release, detected in brain areas during behavioral tasks designed to tax attentional processes, demonstrates that an activation of cholinergic neurons underlies arousal and attention. Since arousal and attention depend on activation of the forebrain cholinergic system, it is to be expected that the loss of cholinergic neurons occurring in AD may lead to impairment of the attentional processes. Indeed, a consensus exists that attention is the first non-memory domain to be affected in AD, before deficits in language and visuo-spatial functions. The difficulties with daily living, which occur even in mild AD, may be related to attentional deficits. ChEIs, by restoring the cholinergic activity, should improve attention. If the cognitive changes resulting from ChEI treatment in AD patients are assessed with appropriate tests or selected items of the scales, a predominant effect on attention and executive functions emerges. In a group of 121 subjects with mild to moderate AD, (MMSE score 21.88 ± 3.63) followed in the Alzheimer Unit in Florence, after a year of treatment with standard doses of ChEIs, it was observed a stabilization of the disease, characterized by no changes of the tests evaluating attention and executive functions but a worsening of those involving memory mechanisms. These findings suggest that ChEI treatment preserves attention more than memory. Finally, the electrophysiological and neurochemical mechanisms through which the activation of the cholinergic forebrain neurons enhance attention and create the condition for information acquisition are reviewed.