Memory decline in down syndrome and its relationship to iPF2alpha, a urinary marker of oxidative stress

Background: Lipid peroxidation may be a marker of free-radical-mediated injury associated with Alzheimer's disease (AD). We aimed to investigate whether changes in lipid peroxidation is associated with cognitive decline in individuals with Down syndrome over a 4-year period.

Methods: Thirty-two adults with DS participated in a longitudinal study with urinary isoprostane 8,12-iso-iPF2alpha (iPF2alpha) assays at baseline and four years follow-up. Informants rated their functional ability and memory function and the adults with DS attempted assessments of language skills and memory. Twenty-six individuals completed assessments of memory (Modified Memory Object Task, MOMT), adaptive behavior (ABAS), and receptive vocabulary (British Picture vocabulary, BPVS) at both time-points.

Results: Overall change in iPF2alpha level was negatively correlated with change in the MOMT score (Spearman's Rho = - 0.576, p = 0.006), i.e., increased lipid peroxidation was correlated with worse memory functioning over time. An increase of $0.02 ng/mg creatinine iPF2α had good sensitivity (85.7%), positive predictive value (75%,), specificity (85.7%) and negative predictive value (92.3%) for memory decline.

Conclusion: Change in iPF2alpha over time may have potential as a biomarker for memory decline in Down syndrome and potentially also help to track progression of MCI to AD in the general population.