Promising agents for treating Alzheimer's disease

Key issues related to the pharmacotherapy of Alzheimer's disease (AD) are discussed, and current and investigational agents are described. There are three key issues in the pharmacotherapy of AD. First, there is a need to eliminate or minimize drug-related adverse reactions. Second, concurrent diseases that either resemble AD or complicate its treatment must be addressed. The third issue is the need for pharmacotherapy not only to improve cognitive performance but to treat related symptoms. Current strategies for treating AD usually rely on increasing cholinergic function. To date, cholinesterase inhibitors (ChEIs) are the only agents that have been well studied and that have shown efficacy by improving cognitive deficits and, in some cases, psychiatric and behavioral components of AD. Tacrine is rarely used today; the only other FDA-approved ChEI is donepezil. Many other approaches are under clinical investigation, including selective muscarinic agonists, antioxidants, anti-inflammatory drugs, and estrogen replacement therapy. New drug discovery efforts focus on molecular events believed to be important in the pathogenesis of AD. Future pharmacotherapy will probably involve increased use of ChEIs in combination with drugs that have other mechanisms of action. Current treatment of AD primarily involves ChEI therapy, but other therapeutic options, particularly combination therapies, hold promise.