Therapeutic uses of cholinesterase inhibitors in neurodegenerative diseases

The chapter describes the rationale for therapies in Alzheimer's disease (AD), aspects of their application to clinical disease, and what is learned from the effects of the drugs in neurodegenerative disease. Effective preventive and therapeutic strategies for AD and other age-related neurodegenerative diseases are the most pressing need in modern clinical neurological practice. The multifactorial nature of the etiology of sporadic AD seems to imply a likelihood that the most effective treatment strategies will target several or many of these processes. Indeed, many models of the progression of AD invoke self-reinforcing cycles of cerebral damage that may be checked in part at any one of a number of steps, but that may be best approached by therapeutic strategies that target multiple aspects of disease pathogenesis. Definitive experimental evidence of a role of ACh in the pathogenesis of human neurodegenerative disease may prove elusive, and perhaps unambiguously manifest only in the context of cotreatments with AChEIs and agents that target other aspects of disease. The symptomatic effects of AChEIs alone dictate that they will remain important treatments for AD.