THE COGNITIVE PSYCHOPHARMACOLOGY OF ALZHEIMERS-DISEASE - FOCUS ON CHOLINERGIC SYSTEMS

The primary pathology in Alzheimer's disease (DAT) occurs in the basal forebrain cholinergic system (BFCS), which provides the major choline rgic innervation to the neocortex, hippocampus and amygdala. Consisten t with the 'cholinergic hypothesis' of dementia in DAT, the most effec tive treatments so far developed for DAT are drugs which act to boost the functions of the BFCS. These include the centrally acting cholines terase inhibitor tacrine, and the cholinergic agonist nicotine, acute administration of which leads to an improvement in attentional functio ns, in line with recent animal studies of the role of the BFCS in cogn ition. We conclude that future research should include the development of more potent, longer-lasting, less toxic cholinergic agents, which appear to be the best candidates for alleviating the cognitive symptom atology of DAT. Such drugs may also be useful in the treatment of a nu mber of other cognitive disorders, including Lewy body dementia, atten tion deficit/hyperactivity disorder, and schizophrenia.