Tariot_1997_Postgrad.Med_101_73

Treatment of Alzheimer's disease has in the past been limited to empirical trials of psychotropics for relief of behavioral complications. At present, tacrine and doneprezil are the only FDA-approved antidementia agents available. In the very near future, however, other cholinesterases inhibitors (e.g., ENA 713, metrifonate, long-acting physostigmine) are expected to be approved for clinical use. The evidence at this point suggests that they have modest but meaningful clinical effects and possible long-term benefits. Clinical use of the newer agents is likely to be influenced by their side-effect profiles, which consist largely of cholinergic effects, although without the hepatotoxic effects associated with tacrine. To what extent these agents are accepted by patients and physicians remains to be seen. On the one hand, benefits are modest; on the other, these medications are increasingly safe. Continuing research is clarifying the role of cholinergic therapy in relieving behavioral symptoms, as well as the possible side effects on rates of illness progression, institutionalizaton, and even mortality. In the not-too-distant future, physicians can expect to see a variety of medications, now in early stages of development, that are intended to affect cholinergic systems in other ways. Further down the road, a host of mechanism-based therapeutic strategies, which hope to deal with the first cause of this devastating illness, will have been assessed in clinical trials.