Nicotinic receptors and neurodegenerative dementing diseases: basic research and clinical implications

Nicotinic cholinergic agonists represent a relatively newly developing area for therapeutic intervention in Alzheimer disease (AD) and related neurodegenerative dementias. Loss of cholinergic receptors has been reported not only in AD but also in Parkinson's disease, Lewy body dementia, and progressive supranuclear palsy. Clinical studies suggest that compounds that act to stimulate nicotinic receptors may improve learning and memory in a variety of models of cognitive impairment in animals. Early clinical studies have suggested positive effects on cognition of nicotine in human beings with and without AD. Finally, nicotinic compounds might show the progression of AD, as suggested by preclinical models of cell death as well as epidemiological evidence of a protective effect of smoking in AD and Parkinson's disease.