Therapeutic approaches in the improvement of cognitive performance in Down syndrome: past, present, and future.

Clinical trials with drugs aimed at treatment of Alzheimer disease to decelerate cognitive decline and translated mimetically to demented and young nondemented Down syndrome patients have been unable to demonstrate improvements in cognitive performance and functioning. Unfortunately, results from clinical trials do not support the use of NMDA antagonists like memantine and we should await at the development of safer GABA(A) antagonists to conclude about the efficacy of approaching Down syndrome therapeutics by modulating neurotransmission systems altered in this pathology. The use of folinic acid or antioxidants in DS patients is not supported by scientific evidence and do not provide improvement in cognitive performance to patients. Alternatively to the modulation of neurotransmission systems, future therapeutic approaches should focus at normalizing the expression levels or function of candidate molecules. Epigallocatechin gallate, a green tea polyphenol, that modulates DYRK1A functioning has already shown preliminarily that this approach may prove useful in therapeutics.