The role of cholinergic agents in the management of behavioural disturbances in Alzheimer's disease.

Abstract

Alzheimer's disease (AD) is characterized by progressive cognitive deterioration, neuropsychological or behavioural disturbances, and eventual elementary neurological dysfunction. Changes in these domains lead to a reduced functional ability of the AD patient which results, inevitably, in an increasing dependency of the patient on their carer. Thus, a compromised quality of life for both the patient with AD and the carer ensues. The clinical deterioration in AD is produced by neurochemical deficits (involving cholinergic, noradrenergic and serotonergic systems) and histological changes (neuritic plaques, neurofibrillary tangles and neuronal death) in the brain. The abnormality in cholinergic neurotransmission, by contributing to both the cognitive impairment and possibly the behavioural disturbances of AD patients, has attracted particularly intense scientific attention. Evidence for the involvement of a cholinergic dimension to the behavioural changes of AD includes the following: the induction of AD-like behaviours in normal individuals by administration of anticholinergic drugs; the exaggeration of behavioural disturbances in AD patients by anticholinergic agents; the correlation of the distribution of cholinergic deficits of AD with regions that are relevant to the observed behaviours, i.e. the frontal and temporal regions; and the amelioration of behavioural disturbances in AD patients treated with cholinergic receptor agonists and cholinesterase inhibitors. This article reviews the increasing evidence that, in addition to their effects on the cognitive and functional domains of AD, cholinergic drugs may be considered psychotropic agents and are useful in the treatment of specific disorders with cholinergic deficits such as AD.