Oxidative stress and cognitive ability in adults with Down syndrome

We aimed to study the hypothesis that high levels of superoxide dismutase (SOD1), previously reported in Down syndrome, would be associated with poorer ability on cognitive tests. Compensatory rises in the activity of glutathione peroxidase (GPx) was expected to be associated with better ability, so that a high ratio between SOD1 and GPx was hypothesised to be the best predictor of poorer cognitive performance.

32 adults with Down syndrome between the ages of 18 and 45 years donated blood samples for SOD1 and GPx assays and urine for Isoprostane 8,12-iso-iPF(2alpha)-VI assay, a specific biomarker of lipid peroxidation in vivo. Informants rated functional ability and memory function for all participants, and those adults with DS that was able to, also completed psychometric assessments of language ability and memory.

Neither SOD1 nor GPx were related to the elevated markers of lipid peroxidation previously described in living adults with DS, and our hypothesis that an increased SOD1/GPx ratio would be correlated with worse performance on cognitive or functional measures was not supported. Contrary to our hypothesis, we found that low SOD1/GPx ratios were associated with worse memory ability, which remained after controlling for confounders such as sex, age or nutritional supplements.

The anti-oxidant system in DS is implicated in the cognitive phenotype associated with the chromosomal disorder, but the variations in the phenotype could result from several possible gene or gene product interactions. Much further research is required before it will be possible to counteract the oxidative stress associated with DS.