Assessment of Cognitive Scales to Examine Memory, Executive Function and Language in Individuals with Down Syndrome: Implications of a 6-month Observational Study

Abstract

Down syndrome (DS) is the most commonly identifiable genetic form of intellectual disability. Individuals with DS have considerable deficits in intellectual functioning (i.e., low intellectual quotient, delayed learning and/or impaired language development) and adaptive behavior. Previous pharmacological studies in this population have been limited by a lack of appropriate endpoints that accurately measured change in cognitive and functional abilities. Therefore, the current longitudinal observational study assessed the suitability and reliability of existing cognitive scales to determine which tools would be the most effective in future interventional clinical studies. Subtests of the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS), Cambridge Neuropsychological Test Automated Battery (CANTAB), and Clinical Evaluation of Language Fundamentals-Preschool-2 (CELF-P-2), and the Observer Memory Questionnaire-Parent Form (OMQ-PF), Behavior Rating Inventory of Executive Function®–Preschool Version (BRIEF-P) and Leiter International Performance Scale-Revised were assessed. The results reported here have contributed to the optimization of trial design and endpoint selection for the Phase 2 study of a new selective negative allosteric modulator of the GABAA receptor α5-subtype (Basmisanil), and can be applied to other studies in the DS population.

A Multi-Method Investigation of Pragmatic Development in Individuals With Down Syndrome

“…The preschool version was administered because items were more appropriate for the nonverbal mental ages of the participants with DS. Because a number of participants fell outside of the norming sample, the raw total composite score was used in analyses, consistent with prior studies examining executive functioning in individuals with DS (Daunhauer et al, 2014; Lee et al, 2011; Liogier d’Ardhuy et al, 2015). …”

Improving Memory and Cognition in Individuals with Down Syndrome

“…The CANTAB is a computerized assessment with touch-screen technology designed for individuals aged 4-90 years that is normed with alternate versions. Its memory tasks, such as the PAL, spatial recognition, and spatial span subtests, may be particularly well-suited for individuals with DS [55,56]. The ACTB was developed specifically to assess the cognitive phenotype in DS and includes tests of general cognitive ability and prefrontal, hippocampal, and cerebellar function [57].…”

The Arizona Cognitive Test Battery for Down Syndrome: Test-Retest Reliability and Practice Effects

“…This group determined that test-retest reliability estimates generated in the timeframes required to inform clinical trials were virtually nonexistent in DS (Esbensen et al, this issue). In the time since this working group met, one study has been published describing the psychometrics and usability of neuropsychological measures for clinical trials in this population (d’Ardhuy et al, 2015). Participants in this study were older children and young adults with DS drawn from a large multinational sample.…”

“…Participants in this study were older children and young adults with DS drawn from a large multinational sample. The study authors highlighted some measures that could be useful in the clinical trials context (see Tables 1 and 2 for the Arizona Cognitive Test Battery outcome measures and comparisons with d’Ardhuy et al, 2015). This investigation focused specifically on memory and executive functioning measures, and the tests administered did not cover the full breadth of the neurocognitive phenotype of DS.…”

“…To further establish the adequacy of this battery for use in clinical trials, there remains a need to administer these tests repeatedly in a large sample. Clinical investigations require measures demonstrating adequate reliability and stability across multiple sessions spanning months of time (as in d’Ardhuy et al, 2015; usually 4–24 weeks). Therefore, the goal of the present study was to employ a large sample of individuals with DS ( N =54) to determine the reliability and practice effects of tests in the ACTB for this population.…”