Abstract
Multiple N-methyl-d-aspartate (NMDA) receptor enhancing agents have had promising effects on cognition among patients with dementia. However, the results remain inconsistent. This exploratory meta-analysis investigated the effectiveness of NMDA receptor enhancing agents for cognitive function. PubMed, the Cochrane Central Register of Controlled Trials, and the Cochrane Database of Systematic Reviews were searched for randomized controlled trials (RCTs). Controlled trials assessing add-on NMDA receptor enhancing agent treatment in patients with dementia and using cognition rating scales were eligible and pooled using a random-effect model for comparisons. The standardized mean difference (SMD) was calculated in each study from the effect size; positive values indicated that NMDA receptor enhancing agent treatment improved cognitive function. Funnel plots and the I2 statistic were evaluated for statistical heterogeneity. Moderators were evaluated using meta-regression. We identified 14 RCTs with 2224 participants meeting the inclusion criteria. Add-on NMDA receptor enhancing agents had small positive significant effects on overall cognitive function among patients with dementia (SMD = 0.1002, 95% CI 0.0105–0.1900, P = 0.02860). Subgroup meta-analysis showed patients with Alzheimer’s Disease and trials using the Alzheimer Disease Assessment Scale-cognitive subscale as the primary outcome had small positive significant effects (SMD = 0.1042, 95% CI 0.0076–0.2007, P = 0.03451; SMD = 0.1267, 95% CI 0.0145–0.2388, P = 0.2686). This exploratory meta-analysis showed a very small, positive, and significant effect on overall cognition function in patients with dementia. Studies with larger samples are needed to evaluate different cognitive domains and phases of dementia.
Highlights
Multiple N-methyl-d-aspartate (NMDA) receptor enhancing agents have had promising effects on cognition among patients with dementia
N-methyl-d-aspartate receptor (NMDAR) antagonists have been developed for the treatment of Alzheimer disease (AD), and memantine, an uncompetitive NMDAR partial antagonist, has been approved as an antidementia medication for moderate to severe AD15,16; memantine is not approved for mild AD and Mild cognitive impairment (MCI) because of unsatisfactory efficacy[17]
NMDAR enhancing modulators had a small positive significant effect on overall cognitive function among patients with dementia (SMD = 0.1002, 95% CI 0.0105–0.1900, P = 0.02860; Fig. 2a)
Summary
Multiple N-methyl-d-aspartate (NMDA) receptor enhancing agents have had promising effects on cognition among patients with dementia. This exploratory meta-analysis investigated the effectiveness of NMDA receptor enhancing agents for cognitive function. Controlled trials assessing add-on NMDA receptor enhancing agent treatment in patients with dementia and using cognition rating scales were eligible and pooled using a random-effect model for comparisons. Add-on NMDA receptor enhancing agents had small positive significant effects on overall cognitive function among patients with dementia (SMD = 0.1002, 95% CI 0.0105–0.1900, P = 0.02860). Several trials of NMDAR enhancing agents have been performed to evaluate their effect on cognitive impairment among patients with dementia. A randomized, double-blind, placebo-controlled trial of 60 patients with early-phase AD or MCI reported a larger improvement in the AD Assessment Scale-cognitive subscale (ADAS-cog) score compared with placebo[22]. We conducted a meta-analysis on the cognitive effects of NMDAR enhancing agents in dementia
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