title: D-cycloserine treatment of Alzheimer disease.
abstract: Degeneration of cortical glutamatergic projections may contribute to the cognitive decline in Alzheimer disease (AD). To evaluate whether 1glutamate system stimulation might confer symptomatic benefit, we administered D-cycloserine, a putative partial indirect agonist at certain N-methyl-D-aspartate (NMDA) glutamate receptors, to 12 patients with probable AD. The patients (seven men, five women) had a mean age of 65 +/- 8.4 years; Mini Mental State Examination scores ranged from 15 to 25. A dose escalation phase, in which cycloserine was given in daily oral doses from 25 to 500 mg (total of six dose levels, 1 week per dose), was followed by a "best dose" crossover comparison with placebo under double-blind conditions. The crossover phase consisted of 2 weeks of cycloserine and 2 weeks of placebo, separated by a 1-week washout period. We observed no significant or consistent effect on neuropsychological outcome measures. The results suggest that short-term potentiation of NMDA-mediated glutamatergic transmission may not prove useful in the symptomatic treatment of Alzheimer dementia.
authors.affiliation: Experimental Therapeutics Branch, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland.
authors.forename: C
authors.initials: C
authors.lastname: Randolph
authors.forename: J W
authors.initials: JW
authors.lastname: Roberts
authors.forename: M C
authors.initials: MC
authors.lastname: Tierney
authors.forename: D
authors.initials: D
authors.lastname: Bravi
authors.forename: M M
authors.initials: MM
authors.lastname: Mouradian
authors.forename: T N
authors.initials: TN
authors.lastname: Chase
mesh_terms: D000368:Aged; D000544:Alzheimer Disease / Q000188:drug therapy* / Q000503:physiopathology; D001921:Brain / Q000187:drug effects / Q000503:physiopathology; D003523:Cycloserine / Q000009:adverse effects / Q000627:therapeutic use*; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D005260:Female; D015577:Geriatric Assessment; D006801:Humans; D008297:Male; D008609:Mental Status Schedule; D008875:Middle Aged; D009483:Neuropsychological Tests; D016194:Receptors, N-Methyl-D-Aspartate / Q000187:drug effects* / Q000502:physiology
chemical_list: D016194:Receptors, N-Methyl-D-Aspartate; D003523:Cycloserine