On the Design of Broad-Based Neuropsychological Test Batteries to Assess the Cognitive Abilities of Individuals with Down Syndrome in the Context of Clinical Trials.

Ines Basten,Ana Brandão,Hudson Taylor,Katherine Koenig,Richard Boada,Veridiana Barrionuevo,Alberto Costa

doi:10.3390/brainsci8120205

Abstract

Down syndrome (DS) is the most common genetically-defined cause of intellectual disability. Neurodevelopmental deficits displayed by individuals with DS are generally global, however, disproportionate deficits in cognitive processes that depend heavily on the hippocampus and prefrontal cortex are also well documented. Additionally, DS is associated with relative strengths in visual processing and visuospatial short-term memory, and weaknesses in the verbal domain. Although reports of pharmacological rescuing of learning and memory deficits in mouse models of DS abound in the literature, proving the principle that cognitive ability of persons with DS can be boosted through pharmacological means is still an elusive goal. The design of customized batteries of neuropsychological efficacy outcome measures is essential for the successful implementation of clinical trials of potential cognitive enhancing strategies. Here, we review the neurocognitive phenotype of individuals with DS and major broad-based test batteries designed to quantify specific cognitive domains in these individuals, including the one used in a pilot trial of the drug memantine. The main goal is to illustrate the essential considerations in planning trials to enhance cognitive functions in individuals with DS, which should also have implications for the design of similar studies in individuals with other forms of intellectual disability.

Highlights

Down syndrome (DS) is the set of phenotypic features of variable expressivity that typically results from trisomy 21
We described the range of neurodevelopmental deficits associated with DS and previous neuropsychological test batteries that have been developed for this population
We have critically reviewed the current knowledge on cognitive deficits of individuals with DS and some of the broad-based neuropsychological test batteries that have been used to assess cognitive skills in this population

Summary

Introduction

Down syndrome (DS) is the set of phenotypic features of variable expressivity that typically results from trisomy 21. It was first described by John Langdon Down in 1866 [1], and its genetic basis, an extra chromosome 21, was discovered almost 60 years ago by Jérôme Lejeune, Raymond. DS occurs in 1 in 691 live births [3] and has a prevalence of 1 in 1000. The combined prevalence of DS in the United States and Brazil is estimated to be between 500,000 and. A wide range of studies of individuals with and without DS showed little or no appreciable anatomical differences [8,10]

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