Safety and efficacy of cognitive training plus epigallocatechin-3-gallate in young adults with Down’s syndrome
Reviewer: Dr. Alan Gaby
Author: de la Torre R, et al
Reference: Safety and efficacy of cognitive training plus epigallocatechin-3-gallate in young adults with Down’s syndrome (TESDAD): a double-blind, randomised, placebo-controlled, phase 2 trial. Lancet Neurol 2016;15:801-810.
Design: Randomized double-blind placebo-controlled trial.
Participants: Eighty-four Spanish adults (aged 16-34 years) with Down syndrome.
Study Medication and Dosage: A green tea extract that contained 45% epigallocatechin-3-gallate (EGCG) or placebo. The dosage of EGCG was 9 mg per kg of body weight per day for 12 months. All participants received cognitive training.
Primary Outcome Measure: Various measures of cognitive function.
Key Findings: Compared with placebo, EGCG significantly improved scores on scales that assessed visual recognition memory (p < 0.04), inhibitory control (p = 0.04), and adaptive behavior (p = 0.002). Adverse effects did not differ between groups.
Practice Implications: Individuals with Down syndrome suffer from an accelerated decline in cognitive function, and frequently develop senile dementia of the Alzheimer type by early middle age. The results of the present study demonstrate that administration of EGCG, when used as an adjunct to cognitive training, can improve measures of cognitive function in adults with Down syndrome. EGCG is believed to work by inhibiting the dual-specificity tyrosine-(Y)-phosphorylation regulated kinase 1A (DYRK1A) enzyme, which is overexpressed in people with Down syndrome, and which appears to play a role in the pathogenesis of intellectual deficits in these individuals. While no serious side effects were observed, EGCG in doses only moderately higher than those used in the present study (such as 800 mg per day in patients with multiple sclerosis) resulted in elevations of liver enzymes in some cases after an average of 20 weeks of treatment.[i] Patients being treated with EGCG should therefore have periodic liver function tests.
[i] Lovera J, et al. Polyphenon E, non-futile at neuroprotection in multiple sclerosis but unpredictably hepatotoxic: Phase I single group and phase II randomized placebo-controlled studies. J Neurol Sci 2015;358:46-52.