Safety and preliminary efficacy on cognitive performance and adaptive functionality of epigallocatechin gallate (EGCG) in children with Down syndrome. A randomized phase Ib clinical trial (PERSEUS study).

PURPOSE: Although some caregivers are using epigallocatechin gallate (EGCG) off label in hopes of improving cognition in young adults with Down syndrome (DS), nothing is known about its safety, tolerability, and efficacy in the DS pediatric population. We aimed to evaluate safety and tolerability of a dietary supplement containing EGCG and if EGCG improves cognitive and functional performance. METHODS: A total of 73 children with DS (aged 6-12 years) were randomized. Participants received 0.5% EGCG (10 mg/kg daily dose) or placebo for 6 months with 3 months follow up after treatment discontinuation. RESULTS: In total, 72 children were treated and 66 completed the study. A total of 38 participants were included in the EGCG group and 35 in the placebo group. Of 72 treated participants, 62 (86%) had 229 treatment-emergent adverse events (AEs). Of 37 participants in the EGCG group, 13 (35%) had 18 drug-related treatment-emergent AEs and 12 of 35 (34%) from the placebo group had 22 events. In the EGCG group, neither severe AEs nor increase in the incidence of AEs related to safety biomarkers were observed. Cognition and functionality were not improved compared with placebo. Secondary efficacy outcomes in girls point to a need for future work. CONCLUSION: The use of EGCG is safe and well-tolerated in children with DS, but efficacy results do not support its use in this population.

Cognitive and neuromodulation strategies for unhealthy eating and obesity: Systematic review and discussion of neurocognitive mechanisms.

We systematically reviewed research on cognitive training and neuromodulation interventions for reducing food craving/intake, unhealthy diet and weight, and discussed their mechanisms of action. We reviewed 50 studies involving six cognitive trainings: Approach and Attentional Bias Modification, Implementation Intentions, Response Inhibition, Episodic Future Thinking and Working Memory; and four neuromodulation approaches: Transcranial Magnetic Stimulation (TMS), transcranial Direct Current Stimulation (tDCS), Deep Brain Stimulation (DBS) and Neurofeedback. Response Inhibition and Implementation Intentions have shown to reduce unhealthy diet and weight in people with overweight/obesity. Attentional Bias Modification has shown promising results in healthy-weight participants. Brain stimulation of the Dorsolateral Prefrontal Cortex via tDCS and the Hypothalamus via DBS showed benefits for reducing food craving and weight in people with overweight/obesity. Studies quality was generally high, but most trials were short-term and many conducted in healthy-weight samples. Modification of cognitive control and motivational processes/circuits are common mechanisms of beneficial training and neuromodulation interventions, and thus a promising approach for overweight/obesity treatment. Longer duration trials in clinical populations are needed to confirm benefits.