The Effect of S-Adenosylmethionine on Cognitive Performance in Mice: An Animal Model Meta-Analysis

BACKGROUND Alzheimer's disease (AD) is the most frequently diagnosed form of dementia resulting in cognitive impairment. Many AD mouse studies, using the methyl donor S-adenosylmethionine (SAM), report improved cognitive ability, but conflicting results between and within studies currently exist. To address this, we conducted a meta-analysis to evaluate the effect of SAM on cognitive ability as measured by Y maze performance. As supporting evidence, we include further discussion of improvements in cognitive ability, by SAM, as measured by the Morris water maze (MWM). METHODS We conducted a comprehensive literature review up to April 2014 based on searches querying MEDLINE, EMBASE, Web of Science, the Cochrane Library and Proquest Theses and Dissertation databases. We identified three studies containing a total of 12 experiments that met our inclusion criteria and one study for qualitative review. The data from these studies were used to evaluate the effect of SAM on cognitive performance according to two scenarios: 1. SAM supplemented folate deficient (SFD) diet compared to a folate deficient (FD) diet and 2. SFD diet compared to a nutrient complete (NC) diet. Hedge's g was used to calculate effect sizes and mixed effects model meta-regression was used to evaluate moderating factors. RESULTS Our findings showed that the SFD diet was associated with improvements in cognitive performance. SFD diet mice also had superior cognitive performance compared to mice on an NC diet. Further to this, meta-regression analyses indicated a significant positive effect of study quality score and treatment duration on the effect size estimate for both the FD vs SFD analysis and the SFD vs NC analysis. CONCLUSION The findings of this meta-analysis demonstrate efficacy of SAM in acting as a cognitive performance-enhancing agent. As a corollary, SAM may be useful in improving spatial memory in patients suffering from many dementia forms including AD.