PREDICTING RESPONSE TO CHOLINESTERASE-INHIBITORS IN ALZHEIMERS-DISEASE - POSSIBLE APPROACHES

Cholinesterase inhibitors have been more extensively investigated for the treatment of Alzheimer's disease than other medications. Currently, tacrine is the only cholinesterase inhibitor that is approved for marketing in the US, Australia and several European countries. Other cholinesterase inhibitors that are currently in phase II and III clinical trials are likely to become available in the next few years. Although these agents have not been as effective as originally expected, they modestly improve cognitive function and functional activities in a subset of patients with Alzheimer's disease. Potential predictors or response modifiers to cholinesterase inhibitors include demographic, clinical and biological characteristics of patients. The most impressive determinants of clinical response seem to be sufficient dosage, plasma concentrations and cholinesterase inhibition, or the effect on the CNS as indicated by electroencephalography, cerebral blood flow or positron emission tomography (PET). At present, the best approach to the early prediction of response is to treat patients with adequate doses of cholinesterase inhibitor, and to assess for early response within 4 weeks of instituting adequate dosage. However, there is no published basis for withholding medication from a patient because he or she is deemed to have a poor probability of response.