NICOTINIC SYSTEM INVOLVEMENT IN ALZHEIMERS AND PARKINSONS-DISEASES - IMPLICATIONS FOR THERAPEUTICS

Advances in our understanding of the structure, function and distribut ion of nicotinic acetylcholine receptors in the CNS have provided the impetus for new studies examining the role(s) that these receptors and associated processes may play in CNS functions. Further motivation ha s come from the realisation that such receptors must be involved in th e maintenance of cigarette smoking, and from clues provided by studies of degenerative neurological diseases such as Alzheimer's disease and Parkinson's disease, in which the loss of nicotinic receptors has bee n described. Ongoing investigations of the molecular substructure of c entral nicotinic receptors and their pharmacology have begun to open u p new possibilities for novel CNS therapeutics with nicotinic agents. Exploiting these possibilities will require understanding of the role( s) that these receptor systems play in human cognitive, behavioural, m otor and sensory functioning. Clues from careful studies of human cogn ition are beginning to emerge and will provide direction for studies o f potentially therapeutic novel nicotinic agents. Despite the promisin g results of acute studies, few long term studies with nicotine or nic otinic drugs have been performed in dementing disorders. Thus, there i s uncertainty as to whether long term nicotinic treatment will provide sustained cognitive benefit. It is even more uncertain whether such c ognitive benefit will have a significant clinical impact on patients a nd their families. To maximise the potential benefit of long term trea tment with nicotinic agonists (or other cholinergic drugs), we suggest that drug treatment should be combined with cognitive rehabilitation strategies. This will enable patients and/or their families to focus o n the particular cognitive domains that may be improved.