Down Syndrome Research Articles

Различия в спектральной мощности ЭЭГ и поведении детей с аутистическими расстройствами несиндромального происхождения и с синдромом Дауна

<p style="text-align: justify;">The diverse nature of the autistic spectrum disorders group (ASD) may be associated with EEG patterns, which may be specific for different profiles of ASD. Approximately 15% of children with Down syndrome (DS) exhibit autistic features, and the cognitive impairment associated with this syndrome remains unclear. We aimed to explore the potential similarities in behavioral disorders and their EEG correlates between non-syndromic ASD and DS children with comorbid autistic features. Three groups of right-handed boys participated in the experiments: typically developed boys (“control”) — N = 36; mean age = 7.11, SD = 0.86; DS group age N = 15, mean age 7.2 (SD = 0.94), and ASD group; N — 36; mean age — 7.11, SD — 0.86; DS group age N — 15, mean age 7.2 (SD — 0.94), and ASD group; N — 39; mean age — 6.24 (SD — 0.91). Increased theta rhythm spectral power in EEG was found in the frontal and temporal areas, while the alpha rhythm in the occipital area exhibited a reduction in children with DS and ASD as compared with control. The alterations in bioelectric activity, such as increased spectral power f theta in the frontal area and a reduction of EEG spectral power in the occipital alpha band, were partially similar in children with DS and with ASD, albeit less pronounced in DS. A distinctive EEG characteristic of DS was the heightened spectral power of beta rhythm compared to the control group. The Psychoeducational Profile testing in DS revealed inferior results in verbal development (p < 0.05) and cognitive representations (p < 0.05) compared to both the control and ASD groups. However, no differences were found in the total cognitive development scale between DS and ASD. At the behavioral level, impaired verbal and non-verbal intelligence was more prominent in DS than in ASD.</p>

Patterns of tooth agenesis in individuals with Down syndrome: A secondary analysis using the Tooth Agenesis Code.

Tooth agenesis (TA) is common in Down syndrome (DS). It is unknown whether this agenesis occurs in specific patterns, which is important regarding treatment planning and aetiological research. This study aimed to aggregate and analyze patterns of TA, excluding third molars, in individuals with DS using the tooth agenesis code (TAC). The study was designed as a secondary analysis, following STROSA guidelines. The search (MEDLINE-PubMed) and selection process resulted in six included studies encompassing 241 individuals with DS. TA data were systematically converted into TACs and analyzed per dentition, per jaw, and per tooth type. Symmetry was evaluated. The prediction was calculated for oligodontia. In the 155 cases with TA 86 distinct Overall-TAC patterns were identified. The most common patterns were bilateral maxillary lateral incisor agenesis (TAC002.002.000.000;10.3%), bilateral mandibular second premolar agenesis (TAC000.000.016.016;5.8%), and unilateral left maxillary lateral incisor agenesis (TAC000.002.000.000;5.2%). Symmetry in TA patterns was observed in 49.6% of TA cases in the maxilla and 52.3% in the mandible. The simultaneous absence of both mandibular central incisors had a large predictive value for oligodontia (OR12.44;95% CI:4.97-31.84; p<.001). Predominant TA patterns exist in DS. Observation of mandibular central incisor agenesis can promote early diagnosis of oligodontia in DS.

Diet and physical activity modification: impact on adaptive behavior and biochemical measures of children with Down syndrome

Objectives Obesity in children with Down syndrome (DS) has negative implications for behavior. The aim was to assess the influence of weight reduction by diet modification with and without physical therapy sessions on adaptive behavior and some biochemical measures in children with DS with obesity. Methods The study included 100 children with DS (56 males, 44 females; age range: 6–9 (8.5 ± 1.7) years. They were subjected to history taking, clinical examination, and the Vineland adaptive behavior scale. They were randomly divided into two groups: Group I underwent nutritional modification, and Group II was subjected to an added exercise program. The biochemical measures were estimated using the automated chemistry analyzer for blood chemistry (lipids), or ELISA. Results An elevation of behavioral adaptive scores was noticed after the weight reduction, together with a reduction in the levels of triglycerides and an elevation of high-density lipoprotein-C levels. Levels of interleukin I, interleukin 6, and leptin were reduced in both groups. However, the improvement regarding the estimated measures was greater in Group II (p < 0.05). Conclusions Weight reduction in children with DS was beneficial for their adaptive behavior and for adjusting dyslipidemia, along with some measures of inflammation. Combining physical activity with nutritional modification would help in the better advancement of the health and adaptive behavior of children with DS associated with obesity compared with isolated nutritional modification.

An overview of down syndrome

The most prevalent chromosomal disorder linked to intellectual disability is down syndrome, often known as Down's syndrome (DS), which is marked by a number of distinct clinical symptoms. About 1 in 800 newborns globally experience it. Approximately 500 live births are caused by DS each year in the US, while over 200,000 people are affected by the disorder. The first account of the syndrome dates back to 1866 and is credited to the English physician John Langdon Down of Cornwall. When the chromosomal cause of the disorder was identified more than 90 years later, it was termed Down syndrome. Although there is still inequality in access to health care and other supportive services, the potential for the development and socialization of people with Down syndrome has been more widely recognized, and early support for impacted children and their families is extensively adopted. Patients vary greatly in their phenotypic characteristics; intellectual disability is typically moderate but can be mild to severe, and social function is frequently good in comparison to cognitive impairment. Geographical location and ethnic origin also have an impact on the incidence and presentation of DS.

Longitudinal Success of Tonsillectomy for Obstructive Sleep Apnea in Children with Down Syndrome.

Obstructive sleep apnea is common in children with Down syndrome (DS). Tonsillectomy is recommended as the first-line approach in treating children with obstructive sleep apnea (OSA), however, there is limited data on the long-term outcomes in children with DS who undergo tonsillectomy. In this retrospective study, we examined the long-term polysomnographic and symptomatic outcomes in children with DS who underwent tonsillectomy with or without an adenoidectomy (T&A). We hypothesize that the success of T&A to treat OSA in children with DS will diminish with time. A retrospective chart review of children with DS who underwent T&A between 2009 and 2015 was conducted. Inclusion criteria were children with at least 1 postoperative polysomnogram (PSG) within 6 months of T&A with an obstructive apnea/hypopnea index (OAHI) < 5. Outcomes were determined by subsequent clinic visits and postoperative polysomnograms: OAHI ≥ 5, snoring reported during clinic visit and time to reoccurrence. Childrens Hospital Colorado. Of the 57 children with mild OSA at 1st (initial) PSG, 13/40 (33%) children had OAHI ≥ 5 at the 2nd postoperative PSG. Of the 18 patients who underwent a 3rd PSG, 4 (22%) progressed to moderate/severe OSA. A total of 17 patients out of the original 57 (30%) progressed to moderate/severe OSA with the median time for the additional post-op PSG's being 2.3 years. Children with DS who have at most mild OSA (OAHI < 5) following a T&A are at risk for progressing to at least moderate OSA within 2 years after their T&A. A surveillance PSG 2 years following surgery will identify these children.

Parent-reported genetic counselor adherence to the NSGC practice resource for communicating a potential prenatal diagnosis: Impact on the Down syndrome diagnosis experience.

In 2011, the National Society of Genetic Counselors (NSGC) published practice resources about communicating a prenatal or postnatal diagnosis of Down syndrome (DS). However, the impact of GC adherence to those recommendations on patient experiences has been unknown. The objective of this analysis was to investigate perceived GC adherence to professional recommendations for delivering a DS diagnosis and the impact on parental diagnosis experiences and the information and support offered. Parents of children with DS born between 2016 and 2021 completed a survey distributed by 12 local DS organizations and the national DS Diagnosis Network to assess prenatal diagnosis experiences and the provision of support and information by health professionals. Participants were queried about whether their GC followed specific recommendations from the NSGC practice resource. Respondents were also invited to describe their diagnosis experience. An overall perceived adherence score was calculated (percentage of elements GC demonstrated/total number of elements). Open-ended responses were inductively coded by a GC and GC student to identify categories and to perform a sentiment analysis where 1 was completely negative, 2 was mixed/more negative, 3 was neutral, 4 was mixed/more positive, and 5 was completely positive. The GCs were blinded to participants' perceived adherence scores while performing the sentiment analysis. Of the 242 parents who completed the survey, 161 respondents answered questions about GC's perceived practice resource adherence. The median perceived adherence score was 42.9% (IQR 21.4-71.4)%. A total of 61 people provided an open-ended response about their prenatal diagnosis experience with a GC and were assigned a sentiment score. The median sentiment score was 3 (IQR 1-5). Kendall's Tau analysis showed that higher perceived practice resource adherence was associated with more positive sentiment scores. These results suggest that NSGC practice resource adherence may improve the prenatal diagnosis experiences of parents of children with DS and have the potential to improve counseling outcomes.

TransPhoM-DS Study Grant Report: Rationale and Protocol for Investigating the Efficacy of Low-Power Transcranial Photobiomodulation on Language, Executive Function, Attention, and Memory in Down Syndrome

Down syndrome (DS) is the leading genetic cause of intellectual disability globally, affecting about 1 in every 800 births. Individuals with DS often face various neuropsychiatric conditions alongside intellectual disabilities due to altered brain development. Despite the diverse phenotypic expressions of DS, typical physical characteristics frequently influence language development and acquisition. EEG studies have identified abnormal oscillatory patterns in individuals with DS. Emerging interventions targeting the enhancement of gamma (40 Hz) neuronal oscillations show potential for improving brain electrical activity and cognitive functions in this population. However, effective cognitive interventions for DS remain scarce. Extensive research indicates that transcranial photobiomodulation (t-PBM) with near-infrared (NIR) light can penetrate deeply into the cerebral cortex, modulate cortical excitability, and enhance cerebral perfusion and oxygenation. Furthermore, t-PBM has been shown to improve cognitive functions such as language, attention, inhibition, learning, and memory, including working memory. This study presents the rationale and design of an ongoing randomized, sham-controlled clinical trial aimed at assessing the effectiveness of t-PBM using NIR light in enhancing the language abilities of individuals with DS.

Down syndrome and postoperative hemodynamics in patients undergoing surgery for congenital cardiac communications

Although Down syndrome (DS) is considered a risk factor for hemodynamic instabilities (mainly pulmonary hypertension–PH) following surgery for congenital cardiac communications, many DS patients do surprising well postoperatively. We prospectively analyzed perioperative factors for a possible correlation with post-cardiopulmonary bypass (CPB) inflammatory reaction and postoperative PH in pediatric subjects. Sixty patients were enrolled (age 3 to 35 months), 39 of them with DS. Clinical and echocardiographic parameters (anatomical and hemodynamic) were computed preoperatively. Pulmonary and systemic mean arterial pressures (PAP and SAP) were assessed invasively intra and postoperatively. Immediate postoperative PAP/SAP ratio (PAP/SAPIPO) and the behavior of pressure curves were selected as primary outcome. Serum levels of 36 inflammatory proteins were measured by chemiluminescence preoperatively and 4 h post CPB. Of all factors analyzed, peripheral oxygen saturation (O2Sat, bedside assessment) was the only preoperative predictor of PAP/SAPIPO at multivariate analysis (p = 0.007). Respective values in non-DS, DS/O2Sat ≥ 95% and DS/O2Sat < 95% subgroups were 0.34 (0.017), 0.40 (0.027) and 0.45 (0.026), mean (SE), p = 0.004. The difference between non-DS and DS groups regarding postoperative PAP curves (upward shift in DS patients, p = 0.015) became nonsignificant (p = 0.114) after adjustment for preoperative O2Sat. Post-CPB levels of at least 5 cytokines were higher in patients with O2Sat < 95% versus those at or above this level, even within the DS group (p < 0.05). Thus, a baseline O2Sat < 95% representing pathophysiological phenomena in the airways and the distal lung, rather than DS in a broad sense, seems to be associated with post-CPB inflammation and postoperative PH in these patients.

Amyloid-β peptide signature associated with cerebral amyloid angiopathy in familial Alzheimer’s disease with APPdup and Down syndrome

Alzheimer’s disease (AD) is characterized by extracellular amyloid plaques containing amyloid-β (Aβ) peptides, intraneuronal neurofibrillary tangles, extracellular neuropil threads, and dystrophic neurites surrounding plaques composed of hyperphosphorylated tau protein (pTau). Aβ can also deposit in blood vessel walls leading to cerebral amyloid angiopathy (CAA). While amyloid plaques in AD brains are constant, CAA varies among cases. The study focuses on differences observed between rare and poorly studied patient groups with APP duplications (APPdup) and Down syndrome (DS) reported to have higher frequencies of elevated CAA levels in comparison to sporadic AD (sAD), most of APP mutations, and controls. We compared Aβ and tau pathologies in postmortem brain tissues across cases and Aβ peptides using mass spectrometry (MS). We further characterized the spatial distribution of Aβ peptides with MS-brain imaging. While intraparenchymal Aβ deposits were numerous in sAD, DS with AD (DS-AD) and AD with APP mutations, these were less abundant in APPdup. On the contrary, Aβ deposits in the blood vessels were abundant in APPdup and DS-AD while only APPdup cases displayed high Aβ deposits in capillaries. Investigation of Aβ peptide profiles showed a specific increase in Aβx-37, Aβx-38 and Aβx-40 but not Aβx-42 in APPdup cases and to a lower extent in DS-AD cases. Interestingly, N-truncated Aβ2-x peptides were particularly increased in APPdup compared to all other groups. This result was confirmed by MS-imaging of leptomeningeal and parenchymal vessels from an APPdup case, suggesting that CAA is associated with accumulation of shorter Aβ peptides truncated both at N- and C-termini in blood vessels. Altogether, this study identified striking differences in the localization and composition of Aβ deposits between AD cases, particularly APPdup and DS-AD, both carrying three genomic copies of the APP gene. Detection of specific Aβ peptides in CSF or plasma of these patients could improve the diagnosis of CAA and their inclusion in anti-amyloid immunotherapy treatments.

Daytime Sleep Problems Are Related to Fine Motor Function in Persons with Down Syndrome

ABSTRACT Given the high prevalence of sleep problems and fine motor deficits that have been reported in persons with Down syndrome (DS), this study was to investigate the effect of sleep-related problems occurring during the day on fine motor function (i.e. manual dexterity and handgrip strength) in persons with DS. We also tested the moderating role of obstructive sleep apnoea (OSA) in the link between sleep-related problems occurring during the day and fine motor function. It was hypothesised that subtle sleep-related problems occurring during the day would significantly predict fine motor performance. Fifty-two persons with DS, aged 13–54, participated and caregivers completed a sleep questionnaire for their children with DS. Hierarchical multiple regression analyses indicated a greater frequency of sleep-related problems occurring during the day significantly predicted greater manual dexterity deficits. Results also suggested that OSA was the moderator for the association between sleep-related problems occurring during the day and manual dexterity. This study has highlighted the importance of exploring sleep problems that might impair fine motor performance for the DS population in their everyday lives. Additional studies are needed to develop effective interventions to promote sleep hygiene and fine motor development in this population.

Insomnia Symptoms Are Associated with Measures of Functional Deterioration and Dementia Status in Adults with Down Syndrome at High Risk for Alzheimer's Disease.

While obstructive sleep apnea (OSA) and insomnia symptoms in neurotypical populations are associated with Alzheimer's disease (AD), their association with dementia in adults with Down syndrome (DS) remains less clear, even though these symptoms are prevalent and treatable in DS. Understanding their associations with AD-related dementia status, cognitive impairment, and functional deterioration may lead to interventions to slow decline or disease progression in adults with DS. To characterize differences in OSA and insomnia symptom expression by dementia status, and to determine which sleep factors support dementia diagnosis. Multimodal consensus conference was used to determine dementia status in 52 adults with DS (52.2 ± 6.4 years, 21 women). Cognitive impairment, adaptive behavior skills, and symptoms of OSA and insomnia were quantified using validated assessments for adults with DS and their primary informants. A sex by dementia status interaction demonstrated that older women with DS and dementia had more severe terminal insomnia but not OSA symptoms relative to older women with DS who were cognitively stable (CS). Greater insomnia symptom severity was associated with greater functional impairments in social and self-care domains adjusting for age, sex, premorbid intellectual impairment, and dementia status. Insomnia symptoms are more severe in women with DS with dementia than in women with DS and no dementia, and regardless of dementia status or sex, more severe insomnia symptoms are associated with greater impairment in activities of daily living. These findings underscore the potential importance of early insomnia symptom evaluation and treatment in women with DS at risk of developing AD.

Comparison of the Amyloid Plaque Proteome in Down Syndrome, Early-Onset Alzheimer's Disease and Late-Onset Alzheimer's Disease.

Down syndrome (DS) is strongly associated with Alzheimer's disease (AD), attributable to APP overexpression. DS exhibits Amyloid-β (Aβ) and Tau pathology similar to early-onset AD (EOAD) and late-onset AD (LOAD). The study aimed to evaluate the Aβ plaque proteome of DS, EOAD and LOAD. Using unbiased localized proteomics, we analyzed amyloid plaques and adjacent plaque-devoid tissue ('non-plaque') from post-mortem paraffin-embedded tissues in four cohorts (n = 20/group): DS (59.8 ± 4.99 y/o), EOAD (63 ± 4.07 y/o), LOAD (82.1 ± 6.37 y/o) and controls (66.4 ± 13.04). We assessed functional associations using Gene Ontology (GO) enrichment and protein interaction networks. We identified differentially abundant Aβ plaque proteins vs. non-plaques (FDR < 5%, fold-change > 1.5) in DS (n = 132), EOAD (n = 192) and in LOAD (n = 128); there were 43 plaque-associated proteins shared between all groups. Positive correlations (p < 0.0001) were observed between plaque-associated proteins in DS and EOAD (R2 = 0.77), DS and LOAD (R2 = 0.73), and EOAD vs. LOAD (R2 = 0.67). Top Biological process (BP) GO terms (p < 0.0001) included lysosomal transport for DS, immune system regulation for EOAD, and lysosome organization for LOAD. Protein networks revealed a plaque enriched signature across all cohorts involving APP metabolism, immune response, and lysosomal functions. In DS, EOAD and LOAD non-plaque vs. control tissue, we identified 263, 269, and 301 differentially abundant proteins, including 65 altered non-plaque proteins across all cohorts. Differentially abundant non-plaque proteins in DS showed a significant (p < 0.0001) but weaker positive correlation with EOAD (R2 = 0.59) and LOAD (R2 = 0.33) compared to the stronger correlation between EOAD and LOAD (R2 = 0.79). The top BP GO term for all groups was chromatin remodeling (DS p = 0.0013, EOAD p = 5.79×10- 9, and LOAD p = 1.69×10- 10). Additional GO terms for DS included extracellular matrix (p = 0.0068), while EOAD and LOAD were associated with protein-DNA complexes and gene expression regulation (p < 0.0001). We found strong similarities among the Aβ plaque proteomes in individuals with DS, EOAD and LOAD, and a robust association between the plaque proteomes and lysosomal and immune-related pathways. Further, non-plaque proteomes highlighted altered pathways related to chromatin structure and extracellular matrix (ECM), the latter particularly associated with DS. We identified novel Aβ plaque proteins, which may serve as biomarkers or therapeutic targets.

Transcranial photobiomodulation for neurodevelopmental disorders: a narrative review.

Neurodevelopmental disorders (NDDs) such as autism spectrum disorder (ASD), attention-deficit/hyperactivity disorder (ADHD), and Down syndrome (DS) significantly impact social, communicative, and behavioral functioning. Transcranial photobiomodulation (t-PBM) with near-infrared light is a promising non-invasive neurostimulation technique for neuropsychiatric disorders, including NDDs. This narrative review aimed to examine the preclinical and clinical evidence of photobiomodulation (PBM) in treating NDDs. A comprehensive search across six databases was conducted, using a combination of MeSH terms and title/abstract keywords: "photobiomodulation", "PBM", "neurodevelopmental disorders", "NDD", and others. Studies applying PBM to diagnosed NDD cases or animal models replicating NDDs were included. Protocols, reviews, studies published in languages other than English, and studies not evaluating clinical or cognitive outcomes were excluded. Nine studies were identified, including one preclinical and eight clinical studies (five on ASD, two on ADHD, and one on DS). The reviewed studies encompassed various t-PBM parameters (wavelengths: 635-905nm) and targeted primarily frontal cortex areas. t-PBM showed efficacy in improving disruptive behavior, social communication, cognitive rigidity, sleep quality, and attention in ASD; in enhancing attention in ADHD; and in improving motor skills and verbal fluency in DS. Minimal adverse effects were reported. Proposed mechanisms involve enhanced mitochondrial function, modulated oxidative stress, and reduced neuroinflammation. t-PBM emerges as a promising intervention for NDDs, with potential therapeutic effects across ASD, ADHD, and DS. These findings underscore the need for further research, including larger-scale, randomized sham-controlled clinical trials with comprehensive biomarker analyses, to optimize treatment parameters and understand the underlying mechanisms associated with the effects of t-PBM.

Assessment and Rehabilitation Intervention of Feeding and Swallowing Skills in Children with Down Syndrome Using the Global Intensive Feeding Therapy (GIFT).

Children with Down syndrome (DS) experience more difficulties with oral motor skills, including chewing, drinking, and swallowing. The present study attempts to measure the preliminary effectiveness of Global Intensive Feeding Therapy (GIFT) in DS. GIFT is a new rehabilitation program addressing the specific difficulties and needs of each child, focusing on sensory and motor oral abilities. It follows an intensive schedule comprising 15 sessions over 5 consecutive days, with 3 sessions per day. The principles of GIFT are applied with specific objectives for DS. GIFT was preliminarily implemented among 20 children diagnosed with DS. To measure the efficacy of GIFT, the Karaduman Chewing Performance Scale (KCPS), the International Dysphagia Diet Standardization Initiative (IDDSI), and the Pediatric Screening-Priority Evaluation Dysphagia (PS-PED) were used. Data were analyzed using the Wilcoxon signed-rank test before (T0) and after intervention (T1) and at one-month follow-up (T2). The effect size was also measured for specific outcomes, using Kendall's W. Our findings revealed that children with DS showed no risk of dysphagia according to the PS-PED (mean score 2.80). Furthermore, statistically significant improvements in chewing performance were observed, as measured by the KCPS (p < 0.01), as well as in texture acceptance and modification, as measured by the IDDSI post-intervention (p < 0.01). For both the KCPS and IDDSI, a large effect size was found (Kendall's W value > 0.8). Parents/caregivers continued using GIFT at home, and this allowed for a positive outcome at the one-month follow-up. GIFT proved to be effective in the rehabilitation of feeding and swallowing disorders in children with DS, as well as for food acceptance.

How trustworthy is online dental information for individuals with Down syndrome from Ibero-American countries?

Internet has become an indispensable source of health-related information. However, several studies have shown there to be a lack of quality control for webpages related to disability. Specifically, available content concerning Down syndrome (DS) and dentistry is limited and of dubious quality. The aim of the present study was to assess the quality of online content in Spanish and Portuguese on dental care for individuals with DS. A simultaneous search in Google and Bing using the terms "Down syndrome" and "odontology/dentist/dental treatment" in Spanish and Portuguese was conducted in seven Ibero-American countries (Argentina, Brazil, Chile, Colombia, Spain, Mexico, and Portugal). The first 100 consecutive pages of results from the three combinations of terms in each of the search engines were accessed and selected by applying conventional exclusion criteria. The selected pages were classified according to their authorship, specificity and dissemination potential. The quality of the online content was assessed using the DISCERN questionnaire and the Questionnaire to Evaluate Health Web Sites According to European Criteria (QEEC). The presence of the Health On Net (HON) and Accredited Medical Website (AMW) seals was also assessed. The mean DISCERN score was 2.51±0.85 and 2.57±0.86 for the Spanish and Portuguese webpages, respectively. The mean readability score was 3.43±1.26 and 3.25±1.08 for the Spanish and Portuguese webpages, respectively. None of the selected webpages presented the HONcode or AMW trust seals. The content available online in Spanish and Portuguese regarding Down syndrome and dentistry is scarce and of highly questionable quality.

Dissecting the contribution of human chromosome 21 syntenic regions to recognition memory processes in adult and aged mouse models of Down syndrome.

Trisomy of human chromosome 21 (Hsa21) results in a constellation of features known as Down syndrome (DS), the most common genetic form of intellectual disability. Hsa21 is orthologous to three regions in the mouse genome on mouse chromosome 16 (Mmu16), Mmu17 and Mmu10. We investigated genotype-phenotype relationships by assessing the contribution of these three regions to memory function and age-dependent cognitive decline, using three mouse models of DS, Dp1Tyb, Dp(17)3Yey, Dp(10)2Yey, that carry an extra copy of the Hsa21-orthologues on Mmu16, Mmu17 and Mmu10, respectively. Prior research on cognitive function in DS mouse models has largely focused on models with an extra copy of the Mmu16 region and relatively little is known about the effects of increased copy number on Mmu17 and Mmu10 on cognition and how this interacts with the effects of aging. As aging is is a critical contributor to cognitive and psychiatric changes in DS, we hypothesised that ageing would differentially impact memory function in Dp1Tyb, Dp(17)3Yey, and Dp(10)2Yey, models of DS. Young (12-13 months and old (18-20 months mice Dp1Tyb, Dp(17)3Yey and Dp(10)2Yey mice were tested on a battery of object recognition memory test that assessed object novelty detection, novel location detection and associative object-in place memory. Following behavioral testing, hippocampal and frontal cortical tissue was analysed for expression of glutamatergic receptor proteins using standard immunoblot techniques. Young (12-13 months and old (18-20 months mice Dp1Tyb, Dp(17)3Yey and Dp(10)2Yey mice were tested on a battery of object recognition memory test that assessed object novelty detection, novel location detection and associative object-in place memory. Following behavioral testing, hippocampal and frontal cortical tissue was analysed for expression of glutamatergic receptor proteins using standard immunoblot techniques. Our results show that distinct Hsa21-orthologous regions contribute differentially to cognitive dysfunction in DS mouse models and that aging interacts with triplication of Hsa21-orthologous genes on Mmu10.

Psychotropic Medication Prescription Patterns in Down Syndrome in a Large Pediatric Specialty Clinic.

Objectives: Patterns of psychotropic medication use in children and adolescents with Down syndrome (DS) are largely unknown. Clinical decisions are often made from evidence and experience from individuals with autism spectrum disorder (ASD) or intellectual disability (ID). Methods: Longitudinal data from 670 children with DS who received care in a specialty DS clinic from March 2021 to February 2024 were collected. After each clinic visit, the clinician indicated the presence or absence of co-occurring neurodevelopmental (ND) or mental health (MH) diagnoses, as well as whether the individual was prescribed a psychopharmacological treatment. We used descriptive statistics and analyzed associations between psychotropic medication use, co-occurring ND/MH conditions, and demographic data. Results: 19.1% of patients were prescribed at least one psychotropic medication at their most recent clinical visit. Alpha-agonists were the most commonly prescribed medication class (30.8%), followed by stimulants (18.9%), and antidepressants (16.7%). There was a significant difference in psychotropic medication use by age, with older children having increased odds of being prescribed a psychotropic medication. There were no differences in psychotropic medication use across sex (p = 0.10), race (p = 0.10), or household income (p = 0.16). Conclusions: We found that one-fifth of patients with DS were prescribed psychotropic medications. Nearly every individual with DS who was prescribed a psychotropic medication had a co-occurring ND/MH condition, yet these rates were lower than what have been reported in children with ID, ASD, and attention deficit/hyperactivity disorder. Further research needs to include those with DS to further understand medication efficacy and safe dosing practices to ensure optimal outcomes.

ZBTB21 suppresses CRE-mediated transcription to impair synaptic function in Down syndrome.

Down syndrome (DS) is the most common chromosomal disorder and a major cause of intellectual disability. The genetic etiology of DS is the extra copy of chromosome 21 (HSA21)-encoded genes; however, the contribution of specific HSA21 genes to DS pathogenesis remains largely unknown. Here, we identified ZBTB21, an HSA21-encoded zinc-finger protein, as a transcriptional repressor in the regulation of synaptic function. We found that normalization of the Zbtb21 gene copy number in DS mice corrected deficits in cognitive performance, synaptic function, and gene expression. Moreover, we demonstrated that ZBTB21 binds to canonical cAMP-response element (CRE) DNA and that its binding to CRE could be competitive with CRE-binding factors such as CREB. ZBTB21 represses CRE-dependent gene expression and results in the negative regulation of synaptic plasticity, learning and memory. Together, our results identify ZBTB21 as a CRE-binding protein and repressor in cAMP-dependent gene regulation, contributing to cognitive defects in DS.

Modeling the impact of neuromorphological alterations in Down syndrome on fast neural oscillations.

Cognitive disorders, including Down syndrome (DS), present significant morphological alterations in neuron architectural complexity. However, the relationship between neuromorphological alterations and impaired brain function is not fully understood. To address this gap, we propose a novel computational model that accounts for the observed cell deformations in DS. The model consists of a cross-sectional layer of the mouse motor cortex, composed of 3000 neurons. The network connectivity is obtained by accounting explicitly for two single-neuron morphological parameters: the mean dendritic tree radius and the spine density in excitatory pyramidal cells. We obtained these values by fitting reconstructed neuron data corresponding to three mouse models: wild-type (WT), transgenic (TgDyrk1A), and trisomic (Ts65Dn). Our findings reveal a dynamic interplay between pyramidal and fast-spiking interneurons leading to the emergence of gamma activity (∼40 Hz). In the DS models this gamma activity is diminished, corroborating experimental observations and validating our computational methodology. We further explore the impact of disrupted excitation-inhibition balance by mimicking the reduction recurrent inhibition present in DS. In this case, gamma power exhibits variable responses as a function of the external input to the network. Finally, we perform a numerical exploration of the morphological parameter space, unveiling the direct influence of each structural parameter on gamma frequency and power. Our research demonstrates a clear link between changes in morphology and the disruption of gamma oscillations in DS. This work underscores the potential of computational modeling to elucidate the relationship between neuron architecture and brain function, and ultimately improve our understanding of cognitive disorders.

Craniofacial and Airway Morphology in Down Syndrome: A Cone Beam Computed Tomography Case Series Evaluation.

Background: Down syndrome (DS) is a genetic condition characterized by an extra copy of chromosome 21, resulting in various physical and cognitive features. This study aimed to comprehensively analyze the dental and craniofacial morphology of individuals with DS using Cone Beam Computed Tomography (CBCT). Methods: Six individuals with DS, comprising five males and one female aged 17 to 35 years, underwent CBCT scanning. Radiographic assessments included dentition, occlusion, paranasal sinuses, airway, skull bones, and suture calcification. Linear and angular cephalometric measurements were performed, and airway analysis was conducted using Dolphin 3D imaging software v.11. Results: The study revealed prognathic maxilla in five patients, prognathic mandible in four, and bimaxillary protrusion in two. Dental findings included microdontia, enamel hypoplasia, and congenitally missing teeth, with maxillary and mandibular third molars most commonly absent. Sinus abnormalities, delayed suture closure, and cervical spine anomalies were also observed. Conclusion: These findings contribute to a deeper understanding of DS-related craniofacial characteristics and emphasize the importance of considering these morphometric features in clinical management strategies for individuals with DS. This study's limited sample size underscores the significance of radiographic assessment in planning interventions such as cosmetic reconstructions, prosthetic rehabilitation, or orthodontic treatment for individuals with DS.