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Cholinesterase Inhibitors for Alzheimer’s Disease

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Abstract

Alzheimer’s disease (AD) is the most common age-related neurodegenerative disease and has become an urgent public health problem in most areas of the world. Substantial progress has been made in understanding the basic neurobiology of AD and, as a result, new drugs for its treatment have become available. Cholinesterase inhibitors (ChEIs), which increase the availability of acetylcholine in central synapses, have become the main approach to symptomatic treatment. ChEIs that have been approved or submitted to the US Food and Drug Administration (FDA) include tacrine, donepezil, metrifonate, rivastigmine and galantamine. In this review we discuss their pharmacology, clinical experience to date with their use and their potential benefits or disadvantages. ChEIs have a significant, although modest, effect on the cognitive status of patients with AD. In addition to their effect on cognition, ChEIs have a positive effect on mood and behaviour. Uncertainty remains about the duration of the benefit because few studies of these compounds beyond one year have been published. Although ChEIs are generally well tolerated, all patients should be followed closely for possible adverse effects. There is no substantial difference in the effectivenes of the various ChEIs, however, they may have different safety profiles. We believe the benefits of their use outweigh the risks and costs and, therefore, ChEIs should be considered as primary therapy for patients with mild to moderate AD.

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Acknowledgements

Supported by National Institute on Aging grants AG03991 and AG05681 and by National Institute of Neurological Disorders and Stroke grant NS34050.

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  1. Alzheimer Disease Research Center and Department of Neurology, Washington University School of Medicine, Campus Box 8111-MDC, 660 South Euclid Avenue, St Louis, Missouri, 63110, USA

    Jaime Grutzendler & John C. Morris

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  1. Jaime Grutzendler
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Correspondence to Jaime Grutzendler.

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Grutzendler, J., Morris, J.C. Cholinesterase Inhibitors for Alzheimer’s Disease. Drugs 61, 41–52 (2001). https://doi.org/10.2165/00003495-200161010-00005

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