Cognitive ability in Down syndrome and its relationship to urinary neopterin, a marker of activated cellular immunity

•Urine neopterin has potential as a biomarker for memory decline in Down syndrome.•Urine neopterin can help to track progression of MCI to Alzheimer’s disease.•The evidence for the role of immune response and oxidative stress in DS is growing. Neopterin is an unconjugated pteridine that is secreted in large quantities by activated macrophages and can be used as a clinical marker of activated cellular immunity and oxidative stress. We aimed to investigate whether urinary neopterin levels are associated with cognitive function in people with Down syndrome (DS). Out of 32 adults with DS who originally participated in a longitudinal study, 25 were followed up at 4 years. Informants rated their adaptive behavior (ABAS) and the adults with DS attempted assessments of language skills and memory at both baseline and follow-up time points (Modified Memory Object Task, MOMT), and receptive vocabulary (British Picture Vocabulary Scale, BPVS). Neopterin/creatinine levels were negatively correlated with change in the MOMT total score (Spearman’s Rho=−0.517, p=0.020) and change in the MOMT delayed recall score (Spearman’s Rho=−0.577, p=0.008) over time, i.e. higher neopterin/creatinine level was associated with worse performance on a test of cognitive ability over time. Urine neopterin may have potential as a biomarker for memory decline in Down syndrome, and could potentially also help to track progression of mild cognitive impairment (MCI) to Alzheimer’s disease in other high risk populations.