There is circumstantial evidence for increased excitotoxicity due to increased glutamatergic stimulation of NMDA receptors in Alzheimer’s disease (AD). Pathologic stimulation of glutamatergic receptors results in abnormally high levels of intracellular calcium and, in vitro, may ultimately lead to cell death. The moderate-to low-affinity N-methyl-D-aspartate (NMDA) receptor antagonist, memantine, has shown benefits on cognitive and functional measures compared with placebo in trials of mixed dementia populations and severe AD.1,2 Memantine has also shown benefit for patients with vascular dementia in double-blind, placebo-controlled studies.3,4 In the study of a severe, mixed population, memantine was associated with reduced care dependence,1 and, in the study of patients with severe AD, it was also associated with pharmacoeconomic benefits.5
The drug was well tolerated, with few or no drug-induced side effects at the doses studied. Although there is no evidence that memantine arrests the progression of AD or mixed AD and vascular dementia (VaD), it appears to slow the progression of disease on multiple outcome measures.