Rationalizing therapeutic approaches in Alzheimer's disease.
Deficits in cholinergic and glutamatergic neurotransmission have been linked to the symptomatology of Alzheimer's disease, and current therapies for Alzheimer's, including cholinesterase inhibitors (ChEIs) and the N-methyl-d-aspartate receptor antagonist memantine, have been developed to compensate for these deficits. This article reviews the results of clinical trials involving agents approved by the United States Food and Drug Administration for use in the treatment of Alzheimer's disease (namely, ChEIs for mild to moderate Alzheimer's and memantine for moderate to severe Alzheimer's). In particular, the efficacy of current monotherapy strategies in the treatment of cognitive and functional symptoms of Alzheimer's disease will be addressed. In addition, data from a clinical trial examining the use of a ChEI in combination with memantine will also be discussed, as it has been hypothesized that ChEIs and memantine may offer synergistic benefits due to their distinct mechanisms of action.
Grossberg
George T
GT
Department of Psychiatry and Human Behavior, Saint Louis University Health Science Center, Wohl Clinic, 1221 South Grand Boulevard, St. Louis, MO 63104, USA. grossbgt@slu.edu
D000203:Activities of Daily Living; D000368:Aged; D000544:Alzheimer Disease / Q000175:diagnosis / Q000188:drug therapy*; D002800:Cholinesterase Inhibitors / Q000627:therapeutic use*; D000077265:Donepezil; D006801:Humans; D007189:Indans / Q000627:therapeutic use*; D008559:Memantine / Q000494:pharmacology* / Q000627:therapeutic use*; D009483:Neuropsychological Tests; D010880:Piperidines / Q000627:therapeutic use*; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors*; D012720:Severity of Illness Index
D002800:Cholinesterase Inhibitors; D007189:Indans; D010880:Piperidines; D016194:Receptors, N-Methyl-D-Aspartate; D000077265:Donepezil; D008559:Memantine