Perspectives in clinical Alzheimer's disease research and the development of antidementia drugs.

Current treatment approaches in Alzheimer's disease are primarily symptomatic, with the major therapeutic strategy based on acetylcholinesterase inhibition. Alzheimer's disease research should advance over ensuing decade(s) to yield better symptomatic therapies, drugs designed to slow the rate of progression, and disease preventing agents. The next generation of cholinergic agents will include long acting cholinesterase inhibitors with a good safety profile and brain specific muscarinic agonists. The most critical advances in Alzheimer's disease treatment, however, will target slowing of disease progression and prevention of dementia. Therapeutic agents are being developed that interfere with the synthesis, deposition and aggregation of beta-amyloid protein. Clinical trials are presently being conducted with small molecules having nerve growth factor like activity (e.g. AIT-082, cerebrolysin). In addition, estrogen, anti-inflammatory agents (e.g. cyclooxygenase inhibitors) and antioxidant approaches (e.g. vitamin E) are currently being proposed or utilized in disease prevention trials.