The Search for Better Noncholinergic Treatment Options for Alzheimer’s Disease

The current recommended standard of care for the symptomatic treatment of mild to moderate Alzheimer’s disease is cholinesterase inhibitors. In short- and long-term studies, the 3 cholinesterase inhibitors most commonly used, donepezil, rivastigmine, and galantamine, have demonstrated efficacy in improving not only cognition but also function and behavior in patients suffering from mild to severe cases of Alzheimer’s disease and other forms of dementia. However, the benefits of cholinesterase inhibitors in treating the broad spectrum of symptoms associated with Alzheimer’s disease are not sustained indefinitely, and the illness continues to progress even while patients are receiving treatment. Additionally, while temporary stabilization may occur, there is typically only a modest improvement from baseline, and side effects from treatment with cholinesterase inhibitors can be too severe for some patients to tolerate. Therefore, additional therapies for Alzheimer’s disease still need to be developed that include more tolerable agents with alternative mechanisms of action and broader efficacy.