Safety, efficacy, and tolerability of memantine for cognitive and adaptive outcome measures in adolescents and young adults with Down syndrome: a randomised, double-blind, placebo-controlled phase 2 trial.

Background: Down syndrome is a chromosomal disorder with considerable neurodevelopmental impact and neurodegenerative morbidity. In a pilot trial in young adults with Down syndrome, memantine (a drug approved for Alzheimer's disease) showed a significant effect on a secondary measure of episodic memory. We aimed to test whether memantine would improve episodic memory in adolescents and young adults with Down syndrome.

Novel DYRK1A Inhibitor Rescues Learning and Memory Deficits in a Mouse Model of Down Syndrome.

Down syndrome (DS) is a complex genetic disorder associated with substantial physical, cognitive, and behavioral challenges. Due to better treatment options for the physical co-morbidities of DS, the life expectancy of individuals with DS is beginning to approach that of the general population. However, the cognitive deficits seen in individuals with DS still cannot be addressed pharmacologically.

High resolution structural and functional MRI of the hippocampus in young adults with Down syndrome.

Down syndrome is the phenotypic consequence of trisomy 21, with clinical presentation including both neurodevelopmental and neurodegenerative components. Although the intellectual disability typically displayed by individuals with Down syndrome is generally global, it also involves disproportionate deficits in hippocampally-mediated cognitive processes. Hippocampal dysfunction may also relate to Alzheimer's disease-type pathology, which can appear in as early as the first decade of life and becomes universal by age 40.

Atypical electrophysiological and behavioral responses to diazepam in a leading mouse model of Down syndrome.

Mounting evidence implicates dysfunctional GABAR-mediated neurotransmission as one of the underlying causes of learning and memory deficits observed in the Ts65Dn mouse model of Down syndrome (DS). The specific origin and nature of such dysfunction is still under investigation, which is an issue with practical consequences to preclinical and clinical research, as well as to the care of individuals with DS and anxiety disorder or those experiencing seizures in emergency room settings. Here, we investigated the effects of GABAR positive allosteric modulation (PAM) by diazepam on brain activity, synaptic plasticity, and behavior in Ts65Dn mice.