Search

Background: The dual task training (DTT) has been shown to improve postural and cognitive performances in many populations. Therefore, it seems of interest to explore the effect of such training modality in individuals with Down syndrome (DS) presenting both cognitive and postural deficits., Aims: This study explored the effect of a DTT compared to a single task training (STT) on postural and cognitive performances in adolescents with DS., Methods and Procedures: The center of pressure velocity (CoP Vm ) and the cognitive performance in the selective word recall test were recorded under single task (ST) and DT conditions before and after 8 weeks in the STT group (STTG), the DTTG and the control group (CG)., Outcomes and Results: Before training, CoP Vm values increased and cognitive performances decreased (p < 0.001) during the DT compared to ST conditions in all groups. After training, CoP Vm decreased (p < 0.001) in the DTTG and the STTG under the ST conditions. However, under DT conditions, these values decreased (p < 0.001) only in the DTTG. The cognitive performance increased (p < 0.001) only in the DTTG in both ST and DT conditions., Conclusion: The DTT is strongly recommended to improve both postural and cognitive performances in individuals with DS notably in DT conditions., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

A hormone enhances cognition in mouse models of Alzheimer's disease and Down syndrome.

At the present time, no viable treatment exists for cognitive and olfactory deficits in Down syndrome (DS). We show in a DS model (Ts65Dn mice) that these progressive nonreproductive neurological symptoms closely parallel a postpubertal decrease in hypothalamic as well as extrahypothalamic expression of a master molecule that controls reproduction-gonadotropin-releasing hormone (GnRH)-and appear related to an imbalance in a microRNA-gene network known to regulate GnRH neuron maturation together with altered hippocampal synaptic transmission. Epigenetic, cellular, chemogenetic, and pharmacological interventions that restore physiological GnRH levels abolish olfactory and cognitive defects in Ts65Dn mice, whereas pulsatile GnRH therapy improves cognition and brain connectivity in adult DS patients. GnRH thus plays a crucial role in olfaction and cognition, and pulsatile GnRH therapy holds promise to improve cognitive deficits in DS.

The Down syndrome (DS) phenotype is usually characterized by relative strengths in non-verbal skills and deficits in verbal processing, but high interindividual variability has been registered in the syndrome. The goal of this study was to explore the cognitive profile, considering verbal and non-verbal intelligence, of children and adolescents with DS, also taking into account interindividual variability. We particularly aimed to investigate whether this variability means that we should envisage more than one cognitive profile in this population. The correlation between cognitive profile and medical conditions, parents' education levels and developmental milestones was also explored. Seventy-two children/adolescents with DS, aged 7-16 years, were assessed with the Wechsler Preschool and Primary Scale of Intelligence-III. Age-equivalent scores were adopted, and Verbal and Non-Verbal indices were obtained for each individual. The cognitive profile of the group as a whole was characterized by similar scores in the verbal and non-verbal domain. Cluster analysis revealed three different profiles, however: one group, with the lowest scores, had the typical profile associated with DS (with higher non-verbal than verbal intelligence); one, with intermediate scores, had greater verbal than non-verbal intelligence; and one, with the highest scores, fared equally well in the verbal and non-verbal domain. Three cognitive profiles emerged, suggesting that educational support for children and adolescents with DS may need to be more specific., (© 2022. The Author(s).)

Adults with Down syndrome (DS) are at risk for Alzheimer's disease. Despite sharing trisomy 21, however, there is variability in the age of disease onset. This variability may mean that other factors, such as lifestyle, influence cognitive aging and disease timing. The present study assessed the association between everyday life physical activity using an actigraph accelerometer and cognitive functioning and early Alzheimer's disease pathology via positron emission tomography amyloid-β and tau and diffusion tension imaging measures of white matter integrity in 61 non-demented adults with DS. Percent time in sedentary behavior and in moderate-to-vigorous activity were associated (negatively and positively, respectively) with cognitive functioning (r = -.472 to .572, p < 0.05). Neither sedentary behavior nor moderate-to-vigorous activity were associated with amyloid-β or tau, but both were associated with white matter integrity in the superior and inferior longitudinal fasciculus (Fractional Anisotropy: r = -.397 to -.419, p < 0.05; Mean Diffusivity: r = .400, p < 0.05). Longitudinal studies are needed to determine if physical activity promotes healthy aging in DS., (Copyright © 2021 Elsevier Inc. All rights reserved.)

This study examined the contribution of the Apgar score at 1 and 5 min after birth to later cognitive functioning in 168 individuals with Down syndrome who were between 6 and 25 years of age at time of cognitive testing. Our results showed that a lower Apgar score at 1 min was related to a worse performance in later cognitive measures of receptive vocabulary, verbal comprehension and production, visual memory and working memory. Results also showed that a lower Apgar score at 5 min was only related to worse later outcomes of verbal comprehension and production and auditory working memory. Our findings suggest a need for future studies investigating how specific perinatal events reflected in the Apgar score are linked to later cognitive functioning in individuals with Down syndrome.

This work investigates the role of metabolite levels in the intellectual impairment of subjects with Down syndrome (DS). Homocysteine, folate, vitamin B12, uric acid (UA), creatinine levels and MTHFR C677T genotype were analyzed in 147 subjects with DS. For 77 subjects, metabolite levels were correlated with cognitive tests. Griffiths-III test was administered to 28 subjects (3.08-6.16 years) and WPPSI-III test was administered to 49 subjects (7.08-16.08 years). Significant correlations were found among some metabolite levels and between homocysteine levels and MTHFR C677T genotype. Moreover, homocysteine, UA and creatinine levels resulted increased with age. We did not find any correlation between metabolites and cognitive test score in the younger group. Homocysteine showed statistically significant correlation with WPPSI-III subtest scores when its level is ≥ 7.35 µmol/L, remaining correlated in higher thresholds only for non-verbal area scores. Vitamin B12 showed correlations with all WPPSI-III subtest scores when its level is < 442 pg/mL. The relevance of the present findings is the detection of a specific metabolite threshold related with a better or worse cognitive score, suggesting that vitamin B12 and homocysteine may have a role in cognitive development in children with DS.

Down syndrome (DS) is the main genetic cause of intellectual disability due to triplication of human chromosome 21 (HSA21). Although there is no treatment for intellectual disability, environmental enrichment (EE) and the administration of green tea extracts containing epigallocatechin-3-gallate (EGCG) improve cognition in mouse models and individuals with DS. Using proteome, and phosphoproteome analysis in the hippocampi of a DS mouse model (Ts65Dn), we investigated the possible mechanisms underlying the effects of green tea extracts, EE and their combination. Our results revealed disturbances in cognitive-related (synaptic proteins, neuronal projection, neuron development, microtubule), GTPase/kinase activity and chromatin proteins. Green tea extracts, EE, and their combination restored more than 70% of the phosphoprotein deregulation in Ts65Dn, and induced possible compensatory effects. Our downstream analyses indicate that re-establishment of a proper epigenetic state and rescue of the kinome deregulation may contribute to the cognitive rescue induced by green tea extracts.

Cognitive inhibition is part of executive functions. When it exercises control over memory processes, it has the function of regulating the accessibility of memories and allows interference to be resolved. The impairment of its functioning has been related to the presence of forgetfulness of relevant information. In this research, we study the functioning of cognitive memory inhibition processes in people with intellectual disabilities in tasks of delayed visual recognition and analyze the influence of age. For this purpose, 36 people with Down syndrome (mean age = 33.44, standard deviation = 7.54, 50% females) and 36 people with neurotypical development (mean age = 33.55, standard deviation = 7.52, 50% females) participated. The results reflected a lower effectiveness in the group of people with Down syndrome, F(1, 68) = 159.09, p < .001, $ {\upeta}&#95;{\mathrm{p}}^2 $ = .70. The people in the group with Down syndrome had difficulties in interference resolution, both in the subgroup of young people (p = .014, $ \hat{\updelta\ } $= 0.88) and in the subgroup of older people (p = .022, $ \hat{\updelta\ } $= 0.67). The impairment of cognitive inhibition in people with Down syndrome warrants the need to develop specific intervention programs for this process.

Background: Cognitive inhibition is one of the executive functions; this process over memory plays a fundamental role in recalling relevant information. The aims of this study were to understand the effects of maintenance load and stimuli on the operation of cognitive inhibition over memory in working memory tasks in adults with Down syndrome., Method: The study included 36 individuals with Down syndrome (mean age = 33.44 years, standard deviation = 7.54 years, 50% women) and 36 individuals with neurotypical development (mean age = 33.55 years, standard deviation = 7.52 years, 50% women). The participants performed a working memory task in which they had to solve an interference problem during the maintenance phase., Results: The Down syndrome group performed worse on cognitive inhibition over memory than the neurotypical development group. Both groups had lower recall with interference and under high-load conditions. In the neurotypical development group, memory was similar with both materials. The Down syndrome group performed better with non-social stimuli than with social stimuli., Conclusions: Understanding the variables that influence cognitive inhibition over memory will help in planning effective interventions for people with Down syndrome. Considering the results, special importance should be placed on work with social stimuli, at least in individuals with Down syndrome., Competing Interests: The authors have declared that no competing interests exist.

Individuals with Down syndrome (DS) show high inter-subject variability in cognitive ability and have an ultra-high risk of developing dementia (90% lifetime prevalence). Elucidating factors underlying variability in cognitive function can inform us about intellectual disability (ID) and may improve our understanding of factors associated with later cognitive decline. Increased neuronal inhibition has been posited to contribute to ID in DS. Combining electroencephalography (EEG) with dynamic causal modeling (DCM) provides a non-invasive method for investigating excitatory/inhibitory mechanisms. Resting-state EEG recordings were obtained from 36 adults with DS with no evidence of cognitive decline. Theta-alpha activity (4-13 Hz) was characterized in relation to general cognitive ability (raw Kaufmann's Brief Intelligence Test second Edition (KBIT-2) score). Higher KBIT-2 was associated with higher frontal alpha peak amplitude and higher theta-alpha band power across distributed regions. Modeling this association with DCM revealed intrinsic self-inhibition was the key network parameter underlying observed differences in 4-13 Hz power in relation to KBIT-2 and age. In particular, intrinsic self-inhibition in right V1 was negatively correlated with KBIT-2. Results suggest intrinsic self-inhibition within the alpha network is associated with individual differences in cognitive ability in adults with DS, and may provide a potential therapeutic target for cognitive enhancement., (© The Author(s) 2019. Published by Oxford University Press.)

Purpose: Children with Down syndrome (DS) typically have marked delays in language development relative to their general cognitive development, with particular difficulties in expressive compared to receptive language. Although early social communication skills, including gestures and joint attention, have been shown to be related to later language outcomes in DS, knowledge is limited as to whether these factors exclusively predict outcomes, or whether other factors (e.g. perceptual and non-verbal skills) are involved. This study addressed this question., Method: Longitudinal data for a group of infants with DS (n = 14) and a group of typically-developing (TD) infants (n = 35) were collected on measures that have been shown to predict language in TD infants and/or those with developmental delays. These included: non-verbal mental ability, speech segmentation skills, and early social communication skills (initiating and responding to joint attention, initiating behavioural requests)., Results: Linear regression analyses showed that speech segmentation and initiating joint attention were the strongest predictors of later language in the TD group, whereas non-verbal mental ability and responding to joint attention were the strongest predictors of later language for infants with DS., Conclusions: Speech segmentation ability may not determine language outcomes in DS, and language acquisition may be more constrained by social communication and general cognitive skills., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Background: Several studies show that socio-economic status (SES) is related to the developmental trajectories of children with typical development (TD). However, few studies have analysed this relationship regarding children with neurodevelopmental disorders such as Down syndrome (DS). In this paper, we analyse the impact of SES in the neurodevelopmental trajectories of children with DS in comparison with children with TD., Method: Cognitive, language, motor and socio-emotional development were assessed in 31 children with DS between the ages of 15 and 80 months from high to low SES backgrounds. Data from this group were compared with data from a sample of 72 children with TD randomly selected from the Longitudinal Survey of Early Childhood. We analyse and compare these two groups using the developmental trajectories method RESULTS: The results show delayed onsets for the four abilities measured in children with DS compared with children with TD from high to low SES. In the comparison of the developmental trajectories, we found that the differences between the neurodevelopmental trajectories in DS and TD vary according to SES. High SES show differences only in language development, while low SES show significant differences in cognitive, language and socio-emotional development., Conclusions: The results indicate that SES is a factor that could impact the developmental trajectories of children with DS. Although the differences between children with DS and with TD are similar at the beginning regardless of SES, the developmental trajectories are slower in children with DS of low SES than in children of high SES. We argue that the differences are related to the complex interaction of several biological and cultural factors associated with SES. Some specific hypotheses about nutrition, health care access, quality of education and parenting practices are presented, but more research in this area is needed to fully understand these results., (© 2018 MENCAP and International Association of the Scientific Study of Intellectual and Developmental Disabilities and John Wiley & Sons Ltd.)

New skills may be learned by active experience (experiential learning or learning by doing) or by observation of others' experience (learning by observation). In general, learning by observation reduces the time and the attempts needed to learn complex actions and behaviors. The present research aimed to compare learning by observation and learning by doing in two clinical populations with different etiology of intellectual disability (ID), as individuals with Down syndrome (DS) and individuals with Williams syndrome (WS), with the hypothesis that specific profiles of learning may be found in each syndrome. To this end, we used a mixture of new and existing data to compare the performances of 24 individuals with DS, 24 individuals with WS and 24 typically developing children on computerized tasks of learning by observation or learning by doing. The main result was that the two groups with ID exhibited distinct patterns of learning by observation. Thus, individuals with DS were impaired in reproducing the previously observed visuo-motor sequence, while they were as efficient as TD children in the experiential learning task. On the other hand, individuals with WS benefited from the observational training while they were severely impaired in detecting the visuo-motor sequence in the experiential learning task (when presented first). The present findings reinforce the syndrome-specific hypothesis and the view of ID as a variety of conditions in which some cognitive functions are more disrupted than others because of the differences in genetic profile and brain morphology and functionality. These findings have important implications for clinicians, who should take into account the genetic etiology of ID in developing learning programs for treatment and education., (© 2017 John Wiley & Sons Ltd.)

Background: Between 250,000 and 400,000 individuals in the United States are diagnosed with Down syndrome (DS). Nearly all adults with DS will develop Alzheimer's disease pathology starting in their thirties. Recent studies suggest that increased physical activity (PA) may be important for maintaining components of cognition, including memory., Objective: The purpose of this study was to evaluate changes in cognitive function after completion of a 12-week exercise intervention in adults with DS., Methods: Participants were randomized to attend 30-minute group exercise sessions 1 or 2 times a week for 12 weeks. The exercise sessions were delivered via video conferencing on a tablet computer to groups of 5-8 participants. Sessions consisted of aerobic based exercises such as walking and jogging to music, dancing, as well as strength based exercises such as vertical jumps, bicep curls, and squats. Cognitive function was measured at baseline and end of study using the Cantab Dementia Battery for iPads, which assessed the cognitive domains of memory, attention, and reaction time., Results: Twenty-seven participants (27.9 ± 7.1 years of age, 40.7% female) enrolled and completed the 12-week intervention. Participants randomized to 1 session/week averaged 26.6 ± 3.0 min/week of PA from the group exercise session. Participants randomized to 2 sessions/week averaged 57.7 ± 15.3 min/week of PA from the group exercise sessions. Participants improved their performance on the two memory variables (p = 0.048 and p = 0.069)., Conclusion: Increased exercise may have positive changes on memory and other cognitive functions., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Individuals with Down syndrome (DS), a genetic condition due to triplication of Chromosome 21, are characterized by intellectual disability that worsens with age. Since impairment of neurogenesis and dendritic maturation are very likely key determinants of intellectual disability in DS, interventions targeted to these defects may translate into a behavioral benefit. While most of the neurogenesis enhancers tested so far in DS mouse models may pose some caveats due to possible side effects, substances naturally present in the human diet may be regarded as therapeutic tools with a high translational impact. Linoleic acid and oleic acid are major constituents of corn oil that positively affect neurogenesis and neuron maturation. Based on these premises, the goal of the current study was to establish whether treatment with corn oil improves hippocampal neurogenesis and hippocampus-dependent memory in the Ts65Dn model of DS. Four-month-old Ts65Dn and euploid mice were treated with saline or corn oil for 30 days. Evaluation of behavior at the end of treatment showed that Ts65Dn mice treated with corn oil underwent a large improvement in hippocampus-dependent learning and memory. Evaluation of neurogenesis and dendritogenesis showed that in treated Ts65Dn mice the number of new granule cells of the hippocampal dentate gyrus and their dendritic pattern became similar to those of euploid mice. In addition, treated Ts65Dn mice underwent an increase in body and brain weight. This study shows for the first time that fatty acids have a positive impact on the brain of the Ts65Dn mouse model of DS. These results suggest that a diet that is rich in fatty acids may exert beneficial effects on cognitive performance in individuals with DS without causing adverse effects., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Recently there has been a practice turn in the philosophy of science that has called for analyses to be grounded in the actual doings of everyday science. This paper is in furtherance of this call and it does so by employing participant-observation ethnographic methods as a tool for discovering epistemological features of scientific practice in a neuroscience lab. The case I present focuses on a group of neurobiologists researching the genetic underpinnings of cognition in Down syndrome (DS) and how they have developed a new mouse model which they argue should be regarded as the "gold standard" for all DS mouse research. Through use of ethnographic methods, interviews, and analyses of publications, I uncover how the lab constructed their new mouse model. Additionally, I describe how model organisms can serve as abstract standards for scientific work that impact the epistemic value of scientific claims, regulate practice, and constrain future work., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Although certain visuospatial abilities, such as mental rotation, are crucially important in everyday activities, they have been little explored in individuals with Down syndrome (DS). This study investigates: i) mental rotation ability in individuals with DS; and ii) its relation to cognitive abilities and to everyday spatial activities. Forty-eight individuals with DS and 48 typically-developing (TD) children, matched on measures of vocabulary and fluid intelligence, were compared on their performance in a rotation task that involved detecting which of two figures would fit into a hole if rotated (five angles of rotation were considered: 0°, 45°, 90°, 135°, 180°). Participants were also assessed on their visuospatial and verbal cognitive abilities, and on their parents and/or educators reports regarding their everyday spatial activities. Results showed that: (i) individuals with DS were less accurate in mental rotation than TD children, with larger differences between the groups for smaller angles of rotation; individuals with DS could not mentally rotate through 180°, while TD children could; (ii) mental rotation ability was related to fluid intelligence and to spatial activities (though other cognitive abilities are also involved in the latter) to a similar degree in the DS group and the matched TD children. These results are discussed with regard to the atypical development domain and spatial cognition models., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

The "difference or delay paradigm" focuses on the question of whether children with developmental disabilities (DD) develop in a way that is only delayed, compared to typically developing children, or also qualitatively different. The current study aimed to examine whether qualitative differences exist in cognitive development of young children with and without DD on the basis of item scores on the Dutch Bayley-III Cognition scale. Differential item functioning was identified for 15 of the 91 items. The presence of DD was related to a higher number of Guttman errors, hinting at more deviation in the order of skill development. An interaction between group (i.e., with or without DD) and developmental quotient appeared to predict the number of Guttman errors. DD was related to a higher number of Guttman errors for the whole range of developmental quotients; children with DD with a small developmental quotient had the highest number. Combined, the results mean that qualitative differences in development are not to be excluded, especially in cases of severe developmental disabilities. When using the Bayley-III in daily practice, the possibility needs to be taken into account that the instruments' assumption of a fixed order in skill development does not hold., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Adults with Down syndrome (DS) have a high incidence of Alzheimer's disease (AD), providing a unique opportunity to explore the early, preclinical stages of AD neuropathology. We examined change in brain amyloid-β accumulation via the positron emission tomography tracer [11C] Pittsburgh compound B (PiB) across 2 data collection cycles, spaced 3 years apart, and decline in cognitive functioning in 58 adults with DS without clinical AD. PiB retention increased in the anterior cingulate gyrus, precuneus cortex, parietal cortex, and anterior ventral striatum. Across the 2 cycles, 14 (27.5%) participants were consistently PiB+, 31 (60.8%) were consistently PiB-, and 6 (11.7%) converted from PiB- at cycle 1 to PiB+ at cycle 2. Increased global amyloid-β was related to decline in verbal episodic memory, visual episodic memory, executive functioning, and fine motor processing speed. Participants who were consistently PiB+ demonstrated worsening of episodic memory, whereas participants who were consistently PiB- evidenced stable or improved performance. Amyloid-β accumulation may be a contributor to or biomarker of declining cognitive functioning in preclinical AD in DS., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Individuals with Down syndrome (DS) are more likely to experience earlier onset of multiple facets of physiological aging. This includes brain atrophy, beta amyloid deposition, cognitive decline, and Alzheimer's disease-factors indicative of brain aging. Here, we employed a machine learning approach, using structural neuroimaging data to predict age (i.e., brain-predicted age) in people with DS (N = 46) and typically developing controls (N = 30). Chronological age was then subtracted from brain-predicted age to generate a brain-predicted age difference (brain-PAD) score. DS participants also underwent [ 11 C]-PiB positron emission tomography (PET) scans to index the levels of cerebral beta amyloid deposition, and cognitive assessment. Mean brain-PAD in DS participants' was +2.49 years, significantly greater than controls (p < 0.001). The variability in brain-PAD was associated with the presence and the magnitude of PiB-binding and levels of cognitive performance. Our study indicates that DS is associated with premature structural brain aging, and that age-related alterations in brain structure are associated with individual differences in the rate of beta amyloid deposition and cognitive impairment., (Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.)

Down syndrome (DS) is caused by three copies of human chromosome 21 (Hsa21) and results in phenotypes including intellectual disability and skeletal deficits. Ts65Dn mice have three copies of ~50% of the genes homologous to Hsa21 and display phenotypes associated with DS, including cognitive deficits and skeletal abnormalities. DYRK1A is found in three copies in humans with Trisomy 21 and in Ts65Dn mice, and is involved in a number of critical pathways including neurological development and osteoclastogenesis. Epigallocatechin-3-gallate (EGCG), the main polyphenol in green tea, inhibits Dyrk1a activity. We have previously shown that EGCG treatment (~10mg/kg/day) improves skeletal abnormalities in Ts65Dn mice, yet the same dose, as well as ~20mg/kg/day did not rescue deficits in the Morris water maze spatial learning task (MWM), novel object recognition (NOR) or balance beam task (BB). In contrast, a recent study reported that an EGCG-containing supplement with a dose of 2-3mg per day (~40-60mg/kg/day) improved hippocampal-dependent task deficits in Ts65Dn mice. The current study investigated if an EGCG dosage similar to that study would yield similar improvements in either cognitive or skeletal deficits. Ts65Dn mice and euploid littermates were given EGCG [0.4mg/mL] or a water control, with treatments yielding average daily intakes of ~50mg/kg/day EGCG, and tested on the multivariate concentric square field (MCSF)-which assesses activity, exploratory behavior, risk assessment, risk taking, and shelter seeking-and NOR, BB, and MWM. EGCG treatment failed to improve cognitive deficits; EGCG also produced several detrimental effects on skeleton in both genotypes. In a refined HPLC-based assay, its first application in Ts65Dn mice, EGCG treatment significantly reduced kinase activity in femora but not in the cerebral cortex, cerebellum, or hippocampus. Counter to expectation, 9-week-old Ts65Dn mice exhibited a decrease in Dyrk1a protein levels in Western blot analysis in the cerebellum. The lack of beneficial therapeutic behavioral effects and potentially detrimental skeletal effects of EGCG found in Ts65Dn mice emphasize the importance of identifying dosages of EGCG that reliably improve DS phenotypes and linking those effects to actions of EGCG (or EGCG-containing supplements) in specific targets in brain and bone., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Objective: The aim of the present study was to examine whether cognitive functioning (i.e., memory and executive functioning) is related to self-reported presence of pain (i.e., affirmative answer to the question whether the individual feels pain) and experience of pain (i.e., intensity and affect) in adults with Down syndrome (DS)., Design, Setting, and Subjects: Cross-sectional study of 224 adults with DS (mean age = 38.1 years, mild-severe intellectual disabilities) in the Netherlands., Methods: File-based medical information was evaluated. Self-reported presence and experience of pain were assessed during a test session, both in rest and after movement (affect with the facial affective scale [FAS], intensity with the numeric rating scale [NRS]). Neuropsychological tests for memory and executive functioning were used., Results: Participants with lower memory scores were more likely to report the presence of pain, while controlling for age, gender, physical conditions that may cause pain, language comprehension, and vocabulary ( p  = .030, 58.4% classification rate, N  = 154). No statistically significant associations were found between executive functioning and self-reported presence of pain or between cognitive functioning and self-reported pain experience., Conclusions: Memory seems to be related to the self-reported presence of pain in adults with DS after explicit inquiry, although the clinical use of this model is yet limited. Therefore, further research is needed for insight into the role of cognitive processes in self-report (e.g., involving aspects such as acquiescence and repeated measurements) to evaluate whether neuropsychological examination could contribute to pain assessment in DS., (© 2016 American Academy of Pain Medicine. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com)

A multisite study investigated the test-retest reliability and practice effects of a battery of assessments to measure neurocognitive function in individuals with Down syndrome (DS). The study aimed to establish the appropriateness of these measures as potential endpoints for clinical trials. Neurocognitive tasks and parent report measures comprising the Arizona Cognitive Test Battery (ACTB) were administered to 54 young participants with DS (7-20 years of age) with mild to moderate levels of intellectual disability in an initial baseline evaluation and a follow-up assessment 3 months later. Although revisions to ACTB measures are indicated, results demonstrate adequate levels of reliability and resistance to practice effects for some measures. The ACTB offers viable options for repeated testing of memory, motor planning, behavioral regulation, and attention. Alternative measures of executive functioning are required.

Few studies on individuals with Down syndrome (DS) have explored how they learn space. The present study examines space learning from verbal descriptions in individuals with DS, and explores the role of external cues (such as a sketch map). Twenty-eight individuals with DS and 28 matched typically-developing (TD) children listened to route or survey descriptions with or without seeing a corresponding sketch map (Description+Sketch Map [D+SM] and Description alone [D], respectively). After hearing each description, they performed tasks that involved recognizing, arranging sequentially, and locating landmarks. The results showed that individuals with DS performed less well in recognizing landmarks and arranging them sequentially. The D+SM condition produced general benefits in both groups' accuracy, though the improvement in locating landmarks was greater in the TD than in the DS group. In both groups, the D+SM condition prompted a better performance than the D condition when participants arranged landmarks sequentially after hearing a description from a route perspective, but not from a survey perspective. Overall, our results show that individuals with DS benefited when a spatial description was associated with a corresponding sketch map, albeit to a lesser degree than TD children. The findings are discussed in the light of the literature on DS and on spatial cognition in the TD domain., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Background: There is conflicting evidence as to whether receptive language abilities of individuals with Down syndrome (DS) continue to improve into adulthood, reach a plateau in late adolescence, or even start to decline., Aim: The study aims to shed light on the question whether receptive syntactic skills change from childhood/adolescence to adulthood and provides a detailed qualitative analysis of the receptive abilities of adults with DS., Methods: 58 individuals with DS participated in the study: 31 children/adolescents (aged: 4;6-19;0 years) and 27 adults (aged: 20;8-40;3 years). They completed measures of grammar comprehension, nonverbal cognition, and phonological working memory., Results: There was no significant correlation between comprehension performance and chronological age in the overall sample. Separate correlational analyses for the subgroups of children/adolescents and adults yielded a significant positive result for the former subgroup but not for the latter. We also found significant positive correlations between grammar comprehension scores and nonverbal mental age as well as measures of phonological working memory. Qualitative analyses showed various limitations in the receptive syntactic abilities of adults with DS. Difficulties increase with sentence length and grammatical complexity, but are also apparent in simple sentences., Conclusion: The results suggest that syntactic comprehension abilities of individuals with DS continue to improve through childhood and adolescence and that thereafter a plateau is reached and maintained. Language comprehension in adults with DS is impaired for a variety of grammatical structures and receptive performance seems to be related to nonverbal cognitive abilities, phonological working memory, and grammatical complexity., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Background: Enhancing cognitive abilities is relevant when devising treatment plans., Aims: This study examined the performance of preschool boys with Down syndrome and fragile X syndrome in cognitive tasks (e.g., nonverbal reasoning and short-term memory), as well as in improving cognitive functions by means of a learning potential methodology., Methods and Procedures: The basic scales corresponding to the Skills and Learning Potential Preschool Scale were administered to children with Down syndrome and others with fragile X syndrome, matched for chronological age and nonverbal cognitive development level., Results: The fragile X syndrome group showed stronger performance on short-term memory tasks than the Down syndrome group prior to intervention, with no differences recorded in nonverbal reasoning tasks. In addition, both groups' cognitive performance improved significantly between pre- and post-intervention. However, learning potential relative to auditory memory was limited in both groups, and for rule-based categorization in Down syndrome children., Conclusion: The scale offered the opportunity to assess young children's abilities and identify the degree of cognitive modifiability. Furthermore, factors that may potentially affect the children's performance before and during learning potential assessment are discussed., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

Down syndrome (DS) is the most common genetic cause of intellectual disability (ID). Abilities relating to executive function, memory and language are particularly affected in DS, although there is a large variability across individuals. People with DS also show an increased risk of developing dementia. While assessment batteries have been developed for adults with DS to assess cognitive abilities, these batteries may not be suitable for those with more severe IDs, dementia, or visual / hearing difficulties. Here we report the development of an informant rated questionnaire, the Cognitive Scale for Down Syndrome (CS-DS), which focuses on everyday abilities relating to executive function, memory and language, and is suitable for assessing these abilities in all adults with DS regardless of cognitive ability. Complete questionnaires were collected about 128 individuals with DS. After final question selection we found high internal consistency scores across the total questionnaire and within the executive function, memory and language domains. CS-DS scores showed a wide range, with minimal floor and ceiling effects. We found high interrater (n = 55) and test retest (n = 36) intraclass correlations. CS-DS scores were significantly lower in those aged 41+ with significant cognitive decline compared to those without decline. Across all adults without cognitive decline, CS-DS scores correlated significantly to measures of general abilities. Exploratory factor analysis suggested five factors within the scale, relating to memory, self-regulation / inhibition, self-direction / initiation, communication, and focussing attention. The CS-DS therefore shows good interrater and test retest reliability, and appears to be a valid and suitable informant rating tool for assessing everyday cognitive abilities in a wide range of individuals with DS. Such a questionnaire may be a useful outcome measure for intervention studies to assess improvements to cognition, in addition to detecting dementia-related cognitive decline. The CS-DS may also be a useful tool for other populations with ID.

One of the most challenging questions in neuroscience is to dissect how learning and memory, the foundational pillars of cognition, are grounded in stable, yet plastic, gene expression states. All known epigenetic mechanisms such as DNA methylation and hydroxymethylation, histone modifications, chromatin remodelling, and noncoding RNAs regulate brain gene expression, both during neurodevelopment and in the adult brain in processes related to cognition. On the other hand, alterations in the various components of the epigenetic machinery have been linked to well-known causes of intellectual disability disorders (IDDs). Two examples are Down Syndrome (DS) and Fragile X Syndrome (FXS), where global and local epigenetic alterations lead to impairments in synaptic plasticity, memory, and learning. Since epigenetic modifications are reversible, it is theoretically possible to use epigenetic drugs as cognitive enhancers for the treatment of IDDs. Epigenetic treatments act in a context specific manner, targeting different regions based on cell and state specific chromatin accessibility, facilitating the establishment of the lost balance. Here, we discuss epigenetic studies of IDDs, focusing on DS and FXS, and the use of epidrugs in combinatorial therapies for IDDs.

Background: This study investigated whether a personalized life story book and rummage box enhanced well-being and led to changes in behaviour for people with Down syndrome (DS) who have dementia., Materials and Methods: A randomized single case series design was used with five participants who had DS and a diagnosis of dementia. Participants were invited to take part in three conditions at random (i) life story book, (ii) rummage box and (iii) no-intervention condition., Results: The two reminiscence conditions were significantly associated with enhanced well-being as compared to the no-intervention condition. However, for one participant, the life story book was associated with significantly higher well-being, while for another participant, the rummage box was associated with significantly higher well-being, suggesting some participants may prefer one method over another., Conclusions: Personalized life story books and rummage boxes are associated with higher levels of well-being for people with DS and dementia., (© 2015 John Wiley & Sons Ltd.)

The present study aims to explore the impact of a numerical skills training program on the basic mathematical skills and logical thinking in children with Down syndrome (DS). The training program was built specifically for children with DS, bearing the strengths and weaknesses of their particular cognitive profile in mind. Two groups of children with DS took part in the study. All children were tested before and after the training on measures of numerical skills and logical thinking. One group of 27 children was trained in numerical skills twice a week for 2 months, for about 30min per session. A control group of 9 children was not involved in any training session. After training, children in the intervention group performed better in numerical tests, while those in the control group did not. These results suggest that our training program is both feasible and effective for children with Down syndrome., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

We have previously reported beneficial effects of acute (i.e., single session) Assisted Cycling Therapy (ACT) on manual dexterity and cognitive planning ability in adolescents with Down syndrome (DS). In the present study, we report the chronic effects of eight weeks of ACT, voluntary cycling (VC), and no cycling (NC), on the same measures in adolescents with DS. Participants completed 8 weeks of ACT, VC, or NC. Those in the ACT and VC groups completed 30min sessions three times per week on a stationary bicycle. During ACT, the mechanical motor of the bicycle augmented the cadence to a rate which was on average 79% faster than the voluntary cadence. During VC, the participants pedaled at a self-selected rate. Unimanual dexterity scores as measured with the Purdue Pegboard test (PPT) improved significantly more for the ACT and VC groups compared to the NC group. ACT lead to greater improvements than VC and NC in the assembly sub-test, which is a task that requires more advanced temporal and spatial processing. The ACT group improved significantly more than the VC group and non-significantly more than the NC group in cognitive planning ability as measured by the Tower of London test (ToL). There were also significant correlations between the assembly subtest of the PPT and all measures of the ToL. These correlations were stronger during post-testing than pre-testing. Pre-post changes in the combined PPT score and ToL number of correct moves correlated positively in the ACT group. These results support the efficacy of the salutary effects of ACT on global fine motor function and executive function in DS. Additionally, the performance on complex bimanual dexterity tasks appears to be related to the capacity of cognitive planning ability. This research has important implications for persons with movement deficits that affect activities of daily living., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

Individuals with Down syndrome (DS) have great difficulty in learning mathematics. In recent years, research has focused on investigating whether precursors of later mathematical competence, such as estimating and comparing numerosities, are preserved in DS. Although studies have suggested a strong relationship between the ability to compare continuous quantities (e.g., area of an object) and that of comparing numerosities, it is still unknown whether this ability is preserved in DS. This study investigated the abilities of individuals with DS to compare area and number and contrasted them with those of two control groups of typically developing individuals. Participants were 16 individuals with DS, 16 typically developing individuals matched by mental age (MA group), and 16 typically developing individuals matched by chronological age (CA group). All participants performed two eye-tracking tasks: an Area Comparison Task (ACT) and a Number Comparison Task (NCT). Stimuli in the two tasks differed in the same ratio to enable comparison of individual performance across both tasks. The results showed that in general, the performance of the three groups was better in the ACT than in the NCT. Critically, performance of individuals with DS in both tasks was consistent with that of individuals with the same MA. The study shows that the abilities to compare area and numerosity are both preserved in DS, and that individuals with this syndrome, like typically developing individuals, show better performance in comparing area than number., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

Individuals with Down syndrome (DS) commonly possess unique neurocognitive and neurobehavioral profiles that emerge within specific developmental periods. These profiles are distinct relative to others with similar intellectual disability (ID) and reflect underlying neuroanatomic findings, providing support for a distinctive phenotypic profile. This review updates what is known about the cognitive and behavioral phenotypes associated with DS across the lifespan. In early childhood, mild deviations from neurotypically developing trajectories emerge. By school-age, delays become pronounced. Nonverbal skills remain on trajectory for mental age, whereas verbal deficits emerge and persist. Nonverbal learning and memory are strengths relative to verbal skills. Expressive language is delayed relative to comprehension. Aspects of language skills continue to develop throughout adolescence, although language skills remain compromised in adulthood. Deficits in attention/executive functions are present in childhood and become more pronounced with age. Characteristic features associated with DS (cheerful, social nature) are personality assets. Children are at a lower risk for psychopathology compared to other children with ID; families report lower levels of stress and a more positive outlook. In youth, externalizing behaviors may be problematic, whereas a shift toward internalizing behaviors emerges with maturity. Changes in emotional/behavioral functioning in adulthood are typically associated with neurodegeneration and individuals with DS are higher risk for dementia of the Alzheimer's type. Individuals with DS possess many unique strengths and weaknesses that should be appreciated as they develop across the lifespan. Awareness of this profile by professionals and caregivers can promote early detection and support cognitive and behavioral development., (© 2015 Wiley Periodicals, Inc.)

Individuals with Down syndrome (DS), a genetic condition caused by triplication of chromosome 21, are characterized by intellectual disability and are prone to develop Alzheimer's disease (AD), due to triplication of the amyloid precursor protein (APP) gene. Recent evidence in the Ts65Dn mouse model of DS shows that enhancement of serotonergic transmission with fluoxetine during the perinatal period rescues neurogenesis, dendritic pathology and behavior, indicating that cognitive impairment can be pharmacologically restored. A crucial question is whether the short-term effects of early treatments with fluoxetine disappear at adult life stages. In the current study we found that hippocampal neurogenesis, dendritic pathology and hippocampus/amygdala-dependent memory remained in their restored state when Ts65Dn mice, which had been neonatally treated with fluoxetine, reached adulthood. Additionally, we found that the increased levels of the APP-derived βCTF peptide in adult Ts65Dn mice were normalized following neonatal treatment with fluoxetine. This effect was accompanied by restoration of endosomal abnormalities, a βCTF-dependent feature of DS and AD. While untreated adult Ts65Dn mice had reduced hippocampal levels of the 5-HT1A receptor (5-HT1A-R) and methyl-CpG-binding protein (MeCP2), a protein that promotes 5-HT1A-R transcription, in neonatally-treated mice both 5-HT1A-R and MeCP2 were normalized. In view of the crucial role of serotonin in brain development, these findings suggest that the enduring outcome of neonatal treatment with fluoxetine may be due to MeCP2-dependent restoration of the 5-HT1A-R. Taken together, results provide new hope for the therapy of DS, showing that early treatment with fluoxetine enduringly restores cognitive impairment and prevents early signs of AD-like pathology., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Experimental research over just the past decade has raised the possibility that learning deficits connected to Down syndrome (DS) might be effectively managed by medication. In the current chapter, we touch on some of the work that paved the way for these advances and discuss the challenges associated with translating them. In particular, we highlight sources of phenotypic variability in the DS population that are likely to impact performance assessments. Throughout, suggestions are made on how to detect meaningful changes in cognitive-adaptive function in people with DS during drug treatment. The importance of within-subjects evaluation is emphasized.

Receptive vocabulary and associated semantic knowledge were compared within and between groups of children with specific language impairment (SLI), children with Down syndrome (DS), and typically developing children. To overcome the potential confounding effects of speech or language difficulties on verbal tests of semantic knowledge, a novel task was devised based on picture-based semantic association tests used to assess adult patients with semantic dementia. Receptive vocabulary, measured by word-picture matching, of children with SLI was weak relative to chronological age and to nonverbal mental age but their semantic knowledge, probed across the same lexical items, did not differ significantly from that of vocabulary-matched typically developing children. By contrast, although receptive vocabulary of children with DS was a relative strength compared to nonverbal cognitive abilities (p < .0001), DS was associated with a significant deficit in semantic knowledge (p < .0001) indicative of dissociation between word-picture matching vocabulary and depth of semantic knowledge. Overall, these data challenge the integrity of semantic-conceptual development in DS and imply that contemporary theories of semantic cognition should also seek to incorporate evidence from atypical conceptual development.

This study was designed to examine longitudinal change in nonverbal cognitive abilities across adolescence for 20 males with Down syndrome (DS). We used hierarchical linear modeling to examine the rate of change in performance on the subtests of the Leiter-R Brief IQ across four annual time points and to determine the relation between maternal IQ and level and rate of change in performance. Results indicated no significant change in IQ (standard scores) with age in the sample, suggesting IQ stability during adolescence for individuals with DS, although several participants performed at floor level on the standard scores for the Leiter-R, limiting interpretation. Growth scores, however, provide a metric of absolute ability level, allow for the examination of change in Leiter-R performance in all participants, and minimize floor effects. Results from the analysis of growth scores indicated significant gain in absolute nonverbal cognitive ability levels (growth score values) over time for the adolescents with DS, although the growth varied by subdomain. Maternal IQ did not explain variability in cognitive performance or change in that performance over time in our sample of adolescents with DS., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

The aim of this study was to examine the effectiveness of 2 modes of exercise on cognitive and upper extremity movement functioning in adolescents with Down syndrome (DS). Nine participants randomly completed 3 interventions over 3 consecutive weeks. The interventions were: (a) voluntary cycling (VC), in which participants cycled at their self-selected pedaling rate; (b) assisted cycling (AC), in which the participants' voluntary pedaling rates were augmented with a motor to ensure the maintenance of 80 rpm; and (c) no cycling (NC), in which the participants sat and listened to music. Manual dexterity improved after AC, but not after VC or NC. Measures of cognitive function, including reaction time and cognitive planning, also improved after AC, but not after the other interventions. Future research will try to uncover the mechanisms involved in the behavioral improvements found after an acute bout of assisted cycling in adolescents with DS.

In the Ts65Dn/DnJ mouse model of Down syndrome (DS), hippocampal deficits of learning and memory are the most robust features supporting this mouse as a valid cognitive model of DS. Although dentate gyrus (DG) dysfunction is suggested by excessive GABAergic inhibition, its role in perturbing DG functions in DS is unknown. We hypothesize that in the Ts65Dn/DnJ mouse, the specific role of the DG is disturbed in its support of contextual and spatial information. Support for this hypothesis comes from rats with DG lesions that show similar deficits. In order to test this hypothesis, we have developed a novel series of spontaneous exploratory tasks that emphasize the importance of recognizing spatial and contextual cues and that involve DG function. The results with this exploratory battery show that Ts65Dn/DnJ mice are impaired in DG-dependent short-term recognition tests involving object recognition with contextual cues, in place recognition and in metric distance recognition relative to wild type littermate controls. Further, whereas Ts65Dn/DnJ mice can recognize object novelty in the absence of contextual cues after a 5-min delay, they cannot do so after a delay of 24 h, suggesting a problem with CA1-mediated consolidation. The results also show that Ts65Dn/DnJ mice are not impaired in tasks (object recognition and configural object recognition) that are mediated by the perirhinal cortex (PRh). These results implicate the DG as a specific therapeutic target and the PRh as a potential therapeutic strength for future research to ameliorate learning and memory in DS., (Copyright © 2013 Wiley Periodicals, Inc.)

The cognitive deficits in Down syndrome (DS) are attributed to an excessive hippocampal inhibition, which obstructs neuronal plasticity and normal learning and memory, a view which is largely based on studies of Ts65Dn mice, the best characterized mouse model of DS. The cognitive behavioral deficits of Ts65Dn mice can be rescued by reducing GABAergic inhibition, most selectively by partial inverse agonists acting on α(5) GABA-A receptors, of which one compound has recently entered clinical trials in DS. Most remarkably, the improved cognitive performance of Ts65Dn can persist for weeks and months after cessation of drug treatment, as demonstrated for the non-specific GABA antagonist pentylenetetrazole. The Alzheimer drugs, memantine and donepezil largely fail to show any benefit. Finally, repeated non-invasive sensory stimulation such as over-training or enriching the environment, are able to enhance the learning performance which underlines the reversibility of an obstructed neuronal plasticity in Ts65Dn mice., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Background: Associations among cognitive development and intrapersonal and environmental characteristics were investigated for 89 longitudinal study participants with Down syndrome to understand developmental patterns associated with cognitive strengths and weaknesses., Materials and Methods: Subtest scores of the Stanford-Binet IV collected between ages 4-30 years were analysed in multilevel models of age-related change. Predictor variables were systematically entered into the models to identify associations with development for each subtest., Results: Temperament, maternal education, medical conditions and school experiences were associated with cognitive differences. Additional associations with rate of development were detected for negative mood, persistence, maternal education level and elementary school experience for several subtests., Conclusions: Early cognitive advantage and consistent opportunities to learn academic content appear to facilitate cognitive development, although this latter was confounded with ability and maternal education in this study. Data presented endorse research into interventions that enhance verbal and problem solving environments through-out early and middle childhood and target reductions in negative affect in relation to supporting cognitive development for individuals with Down syndrome., (© 2012 Blackwell Publishing Ltd.)

In addition to mental retardation, individuals with Down syndrome (DS) also develop the neuropathological changes typical of Alzheimer's disease (AD) and the majority of these individuals exhibit dementia. The Ts65Dn mouse model of DS exhibits key features of these disorders, including early degeneration of cholinergic basal forebrain (CBF) neurons and impairments in functions dependent on the two CBF projection systems; namely, attention and explicit memory. Herein, we demonstrate that supplementing the maternal diet with excess choline during pregnancy and lactation dramatically improved attentional function of the adult trisomic offspring. Specifically, the adult offspring of choline-supplemented Ts65Dn dams performed significantly better than unsupplemented Ts65Dn mice on a series of 5 visual attention tasks, and in fact, on some tasks did not differ from the normosomic (2N) controls. A second area of dysfunction in the trisomic animals, heightened reactivity to committing an error, was partially normalized by the early choline supplementation. The 2N littermates also benefited from increased maternal choline intake on 1 attention task. These findings collectively suggest that perinatal choline supplementation might significantly lessen cognitive dysfunction in DS and reduce cognitive decline in related neurodegenerative disorders such as AD.

Down syndrome is a complex condition that results from having a third copy of human chromosome 21. People with the syndrome experience problems with learning and memory that affect many aspects of their lives. In this issue of Science Translational Medicine, Salehi et al. report on successful drug treatment of learning deficits in an animal model of Down syndrome. This study highlights the function of the norepinephrine-ergic system in Down syndrome and suggests possible treatment options for people with Down syndrome.

This work is aimed at analyzing working memory (WM) components and their relationships with other cognitive processes in individuals with Down syndrome (DS). Particular attention is given to examine whether a verbal WM deficit is due to difficulties in verbal abilities often showed by individuals with DS, or whether it is a deficit per se. A group of 20 individuals with DS was compared to a group of 20 typically developing (TD) children matched on vocabulary comprehension and to a group of 20 TD children matched on general verbal intelligence. The groups received a battery of 3 verbal and 3 visuospatial WM tasks requiring different degrees of control, and tests assessing verbal abilities (WPPSI verbal scale, PPVT), nonverbal skills (WPPSI performance scale), and logical thinking (LO). The results revealed that individuals with DS have deficits in both central executive (control) and verbal components of the WM system, and the latter one is independent of the general verbal abilities deficit. The data suggest that the development of central executive proceeds at a slower rate in individuals with DS and differently from TD children with comparable verbal abilities. The performance of individuals with DS on high-control WM tasks requires additional general resources that are strictly linked to intelligence.

The main goal of this cross-sectional study was to demonstrate that, in addition to a main change during childhood, the cognitive development of children with Down syndrome (DS) is characterized by interindividual variability in their cognitive functioning. Eighty-eight French children with DS took part in this experiment. They were divided into six chronological age groups: 6 years (N=9), 7 years (N=19), 8 years (N=18), 9 years (N=19), 10 years (N=14) and 11 years (N=9). They were assessed by means of the Differential Scales of Intellectual Efficiency. This test, composed of six independent scales, measures verbal abilities and nonverbal reasoning abilities. Initial analyses of the verbal and nonverbal subtest scores indicated a main change in cognitive skills. We then used a clustering approach to identify four cognitive profiles that distinguished the children with DS independently of age and gender. The results confirm that there is a growth in the cognitive skills of DS children. They also suggest that the cognitive functioning of DS children is characterized by different individual profiles. Implications for more fine-tuned research and intervention efforts are discussed.

The contribution of lower level linguistic abilities (study 1) and a higher level capacity, namely the use of context, (study 2), on text comprehension was studied. Participants were 16 individuals with Down syndrome aged between aged between 8 years 11 months and 16 years 10 months, and 16 children with typical development, aged between 5 years 11 months and 7 years 3 months, matched for the level of text comprehension. In study 1 the two groups were compared for receptive vocabulary and sentence comprehension: both of them were shown to play a role in text comprehension in Down syndrome. Since participants with Down syndrome had very low scores in sentence comprehension, study 2 tested the hypothesis that when sentences were presented within a brief context, individuals with Down syndrome would perform better. This hypothesis was confirmed and it was shown that contextual facilitation was closely related to text comprehension skills.

Aims: We aimed to study the hypothesis that high levels of superoxide dismutase (SOD1), previously reported in Down syndrome, would be associated with poorer ability on cognitive tests. Compensatory rises in the activity of glutathione peroxidase (GPx) was expected to be associated with better ability, so that a high ratio between SOD1 and GPx was hypothesised to be the best predictor of poorer cognitive performance., Methods: 32 adults with Down syndrome between the ages of 18 and 45 years donated blood samples for SOD1 and GPx assays and urine for Isoprostane 8,12-iso-iPF(2alpha)-VI assay, a specific biomarker of lipid peroxidation in vivo. Informants rated functional ability and memory function for all participants, and those adults with DS that was able to, also completed psychometric assessments of language ability and memory., Results: Neither SOD1 nor GPx were related to the elevated markers of lipid peroxidation previously described in living adults with DS, and our hypothesis that an increased SOD1/GPx ratio would be correlated with worse performance on cognitive or functional measures was not supported. Contrary to our hypothesis, we found that low SOD1/GPx ratios were associated with worse memory ability, which remained after controlling for confounders such as sex, age or nutritional supplements., Conclusions: The anti-oxidant system in DS is implicated in the cognitive phenotype associated with the chromosomal disorder, but the variations in the phenotype could result from several possible gene or gene product interactions. Much further research is required before it will be possible to counteract the oxidative stress associated with DS.

Background: Standardised neuropsychological and cognitive measures present some limitations in their applicability and generalisability to individuals with intellectual disability (ID). Alternative approaches to defining the cognitive signatures of various forms of ID are needed to advance our understanding of the profiles of strengths and weaknesses as well as the affected brain areas., Aim: To evaluate the utility and feasibility of six non-verbal comparative neuropsychological (CN) tasks administered in a modified version of the Wisconsin General Test Apparatus (WGTA) to confirm and extend our knowledge of unique cognitive signatures of Fragile X syndrome (FXS) and Down syndrome (DS)., Method: A test battery of CN tasks adapted from the animal literature was administered in a modified WGTA. Tasks were selected that have established or emerging brain-behaviour relationships in the domains of visual-perceptual, visual-spatial, working memory and inhibition., Results: Despite the fact that these tasks revealed cognitive signatures for the two ID groups, only some hypotheses were supported. Results suggest that whereas individuals with DS were relatively impaired on visual-perceptual and visual-spatial reversal learning tasks they showed strengths in egocentric spatial learning and object discrimination tasks. Individuals with FXS were relatively impaired on object discrimination learning and reversal tasks, which was attributable to side preferences. In contrast, these same individuals exhibited strengths in egocentric spatial learning and reversal tasks as well as on an object recognition memory task. Both ID groups demonstrated relatively poor performance for a visual-spatial working memory task., Conclusion: Performance on the modified WGTA tasks differentiated cognitive signatures between two of the most common forms of ID. Results are discussed in the context of the literature on the cognitive and neurobiological features of FXS and DS.