The State of The Art on Acetylcholinesterase Inhibitors in the Treatment of Alzheimer's Disease

Alzheimer's disease (AD) is a chronic disabling disease that affects the central nervous system. The main consequences of AD include the decline of cognitive functions and language disorders. One of the causes leading to AD is the decrease of neurotransmitter acetylcholine (ACh) levels in the brain, in part due to a higher activity of acetylcholinesterase (AChE), the enzyme responsible for its degradation. Many acetylcholinesterase inhibitors (AChEIs), both natural and synthetic, have been developed and used through the years to counteract the progression of the disease. The first of such drugs approved for a therapeutic use was tacrine, that binds through a reversible bond to the enzyme. However, tacrine has since been withdrawn because of its adverse effects. Currently, donepezil and galantamine are very promising AChEIs with clinical benefits. Moreover, rivastigmine is considered a pseudo-irreversible compound with anti-AChE action, providing similar effects at the clinical level. The purpose of this review is to provide an overview of what has been published over the last decade on the effectiveness of AChEIs in AD, analysing the most relevant issues under the clinical and methodological profiles and the consequent possible welfare effects for the whole world. Furthermore, novel drugs and possible therapeutic approaches are also discussed.