Cholinesterase inhibitors for Alzheimer's disease

Alzheimer's disease (AD) is the most common age-related neurodegenerative d isease and has become an urgent public health problem in most areas of the world. Substantial progress has been made in understanding the basic neurob iology of AD and, as a result, new drugs for its treatment have become avai lable. Cholinesterase inhibitors (ChEIs), which increase the availability o f acetylcholine in central synapses, have become the main approach to sympt omatic treatment. ChEIs that have been approved or submitted to the US Food and Drug Administration (FDA) include tacrine, donepezil, metrifonate, riv astigmine and galantamine. In this review we discuss their pharmacology, cl inical experience to date with their use and their potential benefits or di sadvantages. ChEIs have a significant, although modest, effect on the cogni tive status of patients with AD. in addition to their effect on cognition, ChEIs have a positive effect on mood and behaviour. Uncertainty remains abo ut the duration of the benefit because few studies of these compounds beyon d one year have been published. Although ChEIs are generally well tolerated , all patients should be followed closely for possible adverse effects. The re is no substantial difference in the effectivenes of the various ChEIs, h owever, they may have different safety profiles. We believe the benefits of their use outweigh the risks and costs and, therefore, ChEIs should be con sidered as primary therapy for patients with mild to moderate AD.