Acetylcholinesterase inhibition in Alzheimer's Disease

Alzheimer's Disease (AD) is the most common cause for dementia in our ageing population, which leads to a slowly progressive, irretrievable ruination of mental function. The destructive, primarily degenerative condition is neuropathologically characterized by the formation of amyloid plaques, neurofibrillary tangles and loss of neurons and synapses as well. Research during the past twenty years revealed early in the disease course a degeneration of cholinergic nuclei localised in the basal forebrain. Impairment of this cholinergic system, which projects into large areas of the limbic system and the neocortex is followed by disturbance of attentional processes and cognitive decline. The link between the cholinergic dysfunction and cognitive impairment has focused large scientific efforts to understand the neurobiology of cognition and to develop therapeutic tools for the fight against Alzheimer's Disease. Acetylcholinesterase inhibitors are currently the best established treatment for this devastating disease. This review describes historical aspects and the vast range of use of cholinesterase inhibitors in traditional societies and industrial nations. Second, the rational basis will be outlined for their development as medication, the so-called cholinergic hypotheses of AD. Third, acetylcholinesterase inhibitors currently available for the treatment of AD will be reviewed. This includes donepezil, galanthamine and rivastigmine. Tacrine, the first acetylcholinesterase inhibitor who became available in 1993 as a treatment for AD, does not play an essential role anymore besides his historical value, because of its hepatotoxicity. Although acetylcholinesterase inhibitors are no cure, these drugs can delay the progress of mental deterioration, reduce neuropsychiatric symptoms and therefore represent a rational therapeutic approach to the treatment of Alzheimer's Disease.