Development and validation of the Arizona Cognitive Test Battery for Down syndrome

Neurocognitive assessment in individuals with intellectual disabilities requires a well-validated test battery. To meet this need, the Arizona Cognitive Test Battery (ACTB) has been developed specifically to assess the cognitive phenotype in Down syndrome (DS). The ACTB includes neuropsychological assessments chosen to 1) assess a range of skills, 2) be non-verbal so as to not confound the neuropsychological assessment with language demands, 3) have distributional properties appropriate for research studies to identify genetic modifiers of variation, 4) show sensitivity to within and between sample differences, 5) have specific correlates with brain function, and 6) be applicable to a wide age range and across contexts. The ACTB includes tests of general cognitive ability and prefrontal, hippocampal and cerebellar function. These tasks were drawn from the Cambridge Neuropsychological Testing Automated Battery (CANTAB) and other established paradigms. Alongside the cognitive testing battery we administered benchmark and parent-report assessments of cognition and behavior. Individuals with DS (n = 74, ages 7–38 years) and mental age (MA) matched controls (n = 50, ages 3–8 years) were tested across 3 sites. A subsample of these groups were used for between-group comparisons, including 55 individuals with DS and 36 mental age matched controls. The ACTB allows for low floor performance levels and participant loss. Floor effects were greater in younger children. Individuals with DS were impaired on a number ACTB tests in comparison to a MA-matched sample, with some areas of spared ability, particularly on tests requiring extensive motor coordination. Battery measures correlated with parent report of behavior and development. The ACTB provided consistent results across contexts, including home vs. lab visits, cross-site, and among individuals with a wide range of socio-economic backgrounds and differences in ethnicity. The ACTB will be useful in a range of outcome studies, including clinical trials and the identification of important genetic components of cognitive disability

Spatial cognition in autism spectrum disorders: superior, impaired, or just intact

The profile of spatial ability is of interest across autism spectrum disorders (ASD) because of reported spatial strengths in ASD and due to the recent association of Asperger’s syndrome with Nonverbal Learning Disability. Spatial functions were examined in relation to two cognitive theories in autism: the central coherence and executive function (EF) theories. Performance on spatial tasks, EFs, and global/local processing was compared in children with ASD and controls. While the ASD group had faster reaction times on the Embedded Figures task, spatial performance was intact, but not superior, on other tasks. There was no evidence for impairments in EF or in processing global/local information, therefore contradicting these two theories. The implications of these results for these two theories are discussed. KEY WORDS: Autism; Asperger’s syndrome; spatial cognition; executive function; central coherence

The extended trajectory of hippocampal development: Implications for early memory development and disorder

Hippocampus has an extended developmental trajectory, with refinements occurring in the trisynaptic circuit until adolescence. While structural change should suggest a protracted course in behavior, some studies find evidence of precocious hippocampal development in the first postnatal year and continuity in memory processes beyond. However, a number of memory functions, including binding and relational inference, can be cortically supported. Evidence from the animal literature suggests that tasks often associated with hippocampus (visual paired comparison, binding of a visuomotor response) can be mediated by structures external to hippocampus. Thus, a complete examination of memory development will have to rule out cortex as a source of early memory competency. We propose that early memory must show properties associated with full function of the trisynaptic circuit to reflect "adult-like" memory function, mainly (1) rapid encoding of contextual details of overlapping patterns, and (2) retention of these details over sleep-dependent delays. A wealth of evidence suggests that these functions are not apparent until 18-24 months, with behavioral discontinuities reflecting shifts in the neural structures subserving memory beginning approximately at this point in development. We discuss the implications of these observations for theories of memory and for identifying and measuring memory function in populations with typical and atypical hippocampal function. (C) 2015 The Authors. Published by Elsevier Ltd.Work on this paper was supported by the National Science Foundation (BCS-1052887) and the National Institutes of Health (R03HD073417) to RLG. The Lumind Research Down Syndrome Foundation, the Bill and Melinda Gates Foundation (OPP1119381), Fondation Jerome Lejeune, the National Institutes of Health (R01HD07434601A1), and the Arizona Alzheimer's Consortium funded JE.This item from the UA Faculty Publications collection is made available by the University of Arizona with support from the University of Arizona Libraries. If you have questions, please contact us at [email protected]

The medial temporal memory system in Down syndrome: Translating animal models of hippocampal compromise

Recent studies have highlighted the dentate gyrus as a region of increased vulnerability in mouse models of Down syndrome (DS). It is unclear to what extent these findings are reflected in the memory profile of people with the condition. We developed a series of novel tasks to probe distinct medial temporal functions in children and young adults with DS, including object, spatial, and temporal order memory. Relative to mental age-matched controls (n=45), individuals with DS (n=28) were unimpaired on subtests involving short-term object or configural recall that was divorced from spatial or temporal contexts. By contrast, the DS group had difficulty recalling spatial locations when contextual information was salient and recalling the order in which objects were serially presented. Results are consistent with dysfunction of spatial and temporal contextual pattern separation abilities in individuals with DS, mediated by the hippocampus, including the dentate gyrus. Amidst increasing calls to bridge human and animal work, the memory profile demonstrated here in humans with DS is strikingly similar to that of the Ts65Dn mouse model of DS. The study highlights the trisynaptic circuit as a potentially fruitful intervention target to mitigate cognitive impairments associated with DS

Remembering things without context: development matters

Spatial context supports memory retrieval in adults. To understand the development of these effects, context effects on object recognition were tested in neurotypical children ages 3 years to adulthood (n 3–6 years = 34, n 10–16 years = 32, n college age = 22) and individuals with Down syndrome (DS) ages 10–29 years (n = 21). Participants engaged in an object recognition task; objects were presented in scenes and either remained in that same scene or were removed at test. In some groups (<4.5 years and with DS) context effects were present even though object recognition was poor. After 4.5 years, children demonstrated memory flexibility, while later in adolescence context effects reemerged, showing nonlinearity in the development of these effects

Young children with Down syndrome show normal development of circadian rhythms, but poor sleep efficiency: a cross-sectional study across the first 60 months of life

Objectives: To evaluate sleep consolidation and circadian activity rhythms in infants and toddlers with Down syndrome (DS) under light and socially entrained conditions within a familiar setting. Given previous human and animal data suggesting intact circadian regulation of melatonin across the day and night, it was hypothesized that behavioral indices of circadian rhythmicity would likewise be intact in the sample with DS. Methods: A cross-sectional study of 66 infants and young children with DS, aged 5e67 months, and 43 typically developing age-matched controls. Sleep and measures of circadian robustness or timing were quantified using continuous in-home actigraphy recordings performed over seven days. Circadian robustness was quantified via time series analysis of rest-activity patterns. Phase markers of circadian timing were calculated alongside these values. Sleep efficiency was also estimated based on the actigraphy recordings. Results: This study provided further evidence that general sleep quality is poor in infants and toddlers with DS, a population that has sleep apnea prevalence as high as 50% during the preschool years. Despite poor sleep quality, circadian rhythm and phase were preserved in children with DS and displayed similar developmental trajectories in cross-sectional comparisons with a typically developing (TD) cohort. In line with past work, lower sleep efficiency scores were quantified in the group with DS relative to TD children. Infants born with DS exhibited the worst sleep fragmentation; however, in both groups, sleep efficiency and consolidation increased across age. Three circadian phase markers showed that 35% of the recruitment sample with DS was phase-advanced to an earlier morning schedule, suggesting significant within-group variability in the timing of their daily activity rhythms. Conclusions: Circadian rhythms of wake and sleep are robust in children born with DS. The present results suggest that sleep fragmentation and any resultant cognitive deficits are likely not confounded by corresponding deficits in circadian rhythms