Memantine is the lone member of the class of NMDA antagonists. Overexcitation of glutamatergic neurons, mediated by NMDA receptors, may be part of the pathophysiology of AD. Thus, blockade of the NMDA receptor can slow cognitive decline. As with ChE-I’s, the benefits of memantine are modest. Memantine is FDA approved for moderate-to-severe AD, although there is evidence to support its use in mild-to-moderate disease. Titration of memantine begins at 5 mg/day for 1 week, then 5 mg twice a day for 1 week, then 10 mg in the morning and 5 mg in the evening for 1 week, then 10 mg twice a day. The maximum dose in renal impairment is 10 mg/day. Memantine is generally well tolerated, with the most common side effects being nausea, dizziness, diarrhea, and agitation. There is mixed evidence regarding the combination of ChE-I and memantine, with the most recent study showing no benefit of adding memantine to a ChE-I.