Rationale for combining glutamatergic and cholinergic approaches in the symptomatic treatment of Alzheimer's disease.

A total of 40 years of biochemical, clinical and neuropathological research have revolutionized our understanding of the pathophysiology of Alzheimer's disease, yet at the present moment the only drugs licensed for treatment are targeted essentially at symptoms. Some disease-modifying drugs remain in clinical trials, but many that have used similar approaches have failed. It is therefore of considerable interest to examine the optimal way of using existing medications for the benefit of patients. This article looks at the rationale behind the combined use of acetylcholinesterase inhibitors and the N-methyl-D-aspartate-receptor antagonist, memantine, from both preclinical and clinical perspectives.