Improved cognition in Alzheimer's disease with short-term D-cycloserine treatment. A preliminary study of D-cycloserine treatment in Alzheimer's disease. Evaluation of cycloserine in the treatment of Alzheimer's disease.
Glutamatergic neurotransmission is important for memory and cognition and is severely affected in Alzheimer's disease. D-Cycloserine exhibits partial agonist activity at the glycine site of N-methyl-D-aspartate subtype glutamate receptor, facilitating activation of the receptor and improving cognition and memory.
                Seventeen patients with Alzheimer's disease received a three-phase, double-blind, placebo-controlled trial of 50 mg and 100 mg/day of D-cycloserine.
                D-Cycloserine was associated with significant improvement in scores on the cognitive subscale of the Alzheimer's Disease Assessment Scale (improvement of 3.0 points) when given at a dose of 100 mg/day.
                D-Cycloserine has cognitive benefits for patients with Alzheimer's disease. D-cycloserine is a partial agonist on the glycine site of the N-methyl-D-aspartate glutamate receptor. This double-blind crossover study of 15 mg D-cycloserine in Alzheimer's disease patients did not demonstrate clinical benefit. Higher medication dosage or long-term treatment may be required. This multicenter study evaluated the efficacy and safety of cycloserine and measured its effects on explicit and implicit memory tests in patients with Alzheimer's disease (AD). Four hundred ten patients with AD, aged 50 years or older, were enrolled in this parallel-group, double-blind, placebo-controlled, randomized trial of 5, 15, or 50 mg cycloserine or placebo twice daily, and 403 entered the double-blind treatment phase. Two hundred sixty-five patients completed the entire 26-week treatment phase. There were no baseline differences among the four treatment groups. Cognitive Drug Research (CDR) efficacy assessments showed no differences between active treatments and placebo from baseline to study weeks 2, 6, 14, or 26. Patients receiving 15 mg of cycloserine improved significantly on one section of an implicit memory test. No differences among treatments were observed for any other assessment scales evaluated. The incidence and severity of adverse events were similar across treatment groups. Cycloserine was well tolerated but did not demonstrate consistent evidence of efficacy during the course of therapy. Higher doses may be necessary to achieve efficacy in the AD population and do not appear to be precluded by the adverse event profile seen in this study.
The lack of a positive effect of D-cycloserine on cognitive outcomes in controlled clinical trials with statistical power high enough to detect a clinically meaningful effect means that D-cycloserine has no place in the treatment of patients with Alzheimer's disease.