Beyond symptomatic therapy: a re-examination of acetylcholinesterase inhibitors in Alzheimer’s disease

Abstract

Acetylcholinesterase inhibitors (AChEIs) are generally regarded as palliative treatments for Alzheimer’s disease that slow the progression of dementia symptoms without altering Alzheimer’s disease’s underlying pathogenic mechanisms. This concept is based on inference rather than evidence, and has limited the scope and persistence of AChEI use in clinical practice. Recent preclinical studies demonstrate that AChEIs exhibit a number of biological effects in addition to cholinesterase inhibition. A broader understanding of the possible mechanisms of action of AChEIs in Alzheimer’s disease could result in more effective use and assist in the development of new and improved therapies. The available evidence brings into question the prevailing view that AChEIs are exclusively symptomatic treatments and supports the use of these agents persistently throughout the course of Alzheimer’s disease.

Keywords::

• acetylcholinesterase inhibitor
• Alzheimer’s disease
• disease modification
• donepezil
• galantamine
• neuroprotection
• rivastigmine

Disclosure

The author has received honoraria for speaking and has served as a consultant for Pfizer Inc. and Eisai Ltd.

Acknowledgements

The genesis of this manuscript is derived from an Aricept^® (donepezil) Neuroprotection Advisory Group meeting, chaired by Norman R Relkin. Eisai Inc. and Pfizer Inc. provided the support for this group, as well the for the academic research discussed in this manuscript. The author acknowledges Marwan Sabbagh for his helpful suggestions in the preparation of this manuscript. Editorial support was provided by Rebecca Mant at PAREXEL and was funded by Pfizer Inc and Eisai Inc.