Down Syndrome Trisomy 21

Obstructive Sleep Apnea (OSA) is characterised by repetitive collapse of the upper airway during sleep, inducing breathing disturbances that can result in oxygen desaturation and frequent arousals. In children, OSA can have long-term consequences on the development and on the cardiovascular system. Down Syndrome (DS) is a genetic disorder associated with intellectual disability and many comorbidities. The prevalence of OSA is particularly high in patients with DS, from infancy. In a recent study, OSA was diagnosed in 97% infants and early diagnosis and intervention from the age of 6 months was associated with better neurocognitive outcome at 3 years old. Therefore, there is a need to develop new strategies to prevent OSA early in infancy. OSA can be linked to some orofacial abnormalities presented by patients with DS. Indeed, orofacial functions and structures ca play a crucial role in OSA. For example, nose breathing allows the tongue to act as a stimulator of the transverse maxillary growth during childhood, allowing the upper airway to develop properly. The primary objective of the present study is to evaluate the effects of a pacifier used by infants with Down Syndrome (from the age of 1 months) on the severity of OSA at the age of 6 months, by comparing a group of infants with the pacifier vs a group of infants without the pacifier. The main hypothesis is that infants who used the pacifier from 1 month- to 6 month-old will have lower OSA severity (estimated by the obstructive apnea hypopnea index on polysomnography (PSG)).

The goal of the ADVANCE (Assay Development and Validation for Pre-Natal and Obstetric Conditions) study is to compare the concordance of results of a novel non-invasive circulating fetal cell (CFC) assay to the results of prenatal invasive diagnostic testing or postnatal genetic and clinical diagnosis of the resulting neonate. This is a prospective study of pregnant individuals.

Adults with Down syndrome (Ds) are often thought to have a lower risk of heart and blood vessel disease because they tend to have lower blood pressure and fewer heart attacks than people without Ds. However, recent research suggests that heart and blood vessel diseases, including stroke, are becoming a more common cause of death in adults with Ds as life expectancy increases. Despite these findings, studies examining heart and blood vessel health in adults with Ds have produced mixed results, making it difficult to determine their true risk and whether preventive strategies are needed. This study will investigate the health of blood vessels in adults with Ds and compare the results with those of adults without Ds. Healthy blood vessels are important because they help deliver blood and oxygen throughout the body. Changes in blood vessel function and stiffness can occur with aging and may increase the risk of heart disease, stroke, kidney disease, and memory problems. The study aims to determine whether adults with Ds experience changes in blood vessel health that may place them at increased cardiovascular risk. Specifically, the study will: (1) Examine how well blood vessels function in adults with Ds; (2) Measure the stiffness of arteries in adults with Ds; (3) Compare two methods used to assess blood vessel function to determine whether a simpler exercise-based test provides results similar to a commonly used standard test. The findings may improve understanding of cardiovascular risk in adults with Ds and help guide future strategies to promote healthy aging in this population.

The goal of this clinical trial is to learn if donanemab can reduce levels of amyloid in the brain, and if donanemab is safe and well-tolerated in participants with Down syndrome. The main questions it aims to answer are: Does donanemab reduce amyloid in the brain? Is donanemab safe and well-tolerated in people with Down syndrome? Researchers will compare donanemab to a placebo (a look-alike substance that contains no drug) to see if donanemab works to reduce levels of amyloid in the brain. Participants in the study will be 35-50 years old and will be in the study for 12 months. Participants will then stay in the study for an additional 12 months in an long-term extension where all participants will receive donanemab. Participants who had a reduction in amyloid (measured by amyloid brain scan) by the end of the first 12 months will receive placebo for the long-term extension, while participants who did not have an amyloid reduction will receive study donanemab for the long-term extension. Everyone (participants and study staff) will remain blinded to treatment for the duration of the study. Participants will: * Have intravenous (IV) infusions of donanemab (or placebo) every 4 weeks * Visit the clinic once every other month for checkups and tests. These tests will include brain scans (magnetic resonance imaging \[MRI\] and positron emission tomography \[PET\] ), blood draws and memory tests. * Have a study partner who who can provide information about the participant and can join participant for some of the study visits.

The goal of this clinical trial is to identify if AEF0217 show an improvement in adaptive behaviors (daily life activities) in adults and older adolescents with Down Syndrome. It will also learn about the safety of AEF0217. The main questions it aims to answer are: * Does AEF0217 improve the daily life activities of the participants after being administered daily for 24 weeks ? * Does AEF0217 improve fluid cognitive function (cognitive abilities that do not depend on prior knowledge) and the crystallised one (knowledge acquired through one's culture, including verbal ability and social knowledge), the quality of life and sleep of the participants after being administered daily for 24 weeks ? * What medical problems do participants have when taking AEF0217? Researchers will compare 3 doses of AEF0217 to a placebo (a look-alike substance that contains no drug) to see if AEF0217 improves adaptative behaviours in people with Down Syndrome. Participants will: * Take AEF0217 or a placebo every day for 24 weeks * Visit the clinic 6 times with their caregiver for checkups, performing tests on a tablet and answering questionnaires. * Be called by phone at home 5 times to check that they are well.

Obstructive Sleep Apnea (OSA) is characterised by repetitive collapse of the upper airway during sleep, inducing breathing disturbances that can result in oxygen desaturation and frequent arousals. In children, OSA can have long-term consequences on the development and on the cardiovascular system. Down Syndrome (DS) is a genetic disorder associated with intellectual disability and many comorbidities. The prevalence of OSA is particularly high in patients with DS, from infancy. In a recent study by Fauroux et al. (2024), OSA was diagnosed in 97% infants and early diagnosis and intervention from the age of 6 months was associated with better neurocognitive outcome at 3 years old. However, polysomnography (PSG - the gold standard method for diagnosing OSA) is poorly accessible, highlighting the need to develop new strategies to prevent and to screen OSA early in infancy. OSA can be linked to some orofacial abnormalities presented by patients with DS. Indeed, orofacial functions and structures ca play a crucial role in OSA. For example, nose breathing allows the tongue to act as a stimulator of the transverse maxillary growth during childhood, allowing the upper airway to develop properly. The primary objective of the present study is to explore the relationships between oro-myo-facial functions, more specifically non-nutritive sucking, and the severity of OSA in 6 months old infants with DS. The main hypothesis is that OSA severity (estimated by the obstructive apnea hypopnea index on PSG) will be negatively correlated to non-nutritive sucking performance. Data from this study could help developing easily accessible protocols for OSA screening based on simple sucking recording. Some interventions could also be tested to prevent OSA from the beginning of life, like an innovative pacifier recently developed by a French start-up to stimulate nose breathing and to promote correct positioning of the tongue.

This observational study evaluates functional and developmental outcomes in pediatric participants undergoing a two week intensive multimodal neurorehabilitation program. The program is designed for children with neurodevelopmental disorders, including but not limited to cerebral palsy, autism spectrum disorder, developmental delay, hypoxic ischemic encephalopathy (HIE), and chromosomal or genetic abnormalities. Participants receive individualized therapy sessions for approximately 2.5 hours per day over a two week period. The intervention is not standardized but is tailored to each child's specific needs and may include components such as sensory integration, motor planning, reflex integration, oculomotor training, executive functioning activities, communication support, and other brain based therapeutic approaches. The purpose of this study is to observe changes in functional abilities, including attention, motor coordination, emotional regulation, communication, and activities of daily living. Outcomes are assessed using clinician observation and parent reported changes before and after the intensive program, with limited follow-up when available. This study does not assign participants to a specific treatment as part of a research protocol. Instead, it collects real world data from children already participating in a clinical therapy program to better understand potential benefits of intensive, individualized neurorehabilitation approaches.

Aim 1 of the proposed project will be to adapt the virtual Mindfulness-Based Therapy for Insomnia (MBTI) for individuals with Down syndrome (DS). The investigators will work closely with a community advisory board consisting of individuals with DS, their caregivers, and clinicians specializing in DS and sleep medicine to ensure that the intervention protocol is relevant and appropriate for young people with DS (age 12 and older). Planned adaptations include 1) utilization of visual aids and videos to increase engagement and reinforce mindfulness concepts and practices; 2) shortened meditation practices to accommodate concentration limits of individuals with DS; 3) caregiver involvement reflecting the important role of caregivers in daily functioning of individuals with DS; 4) adapted homework to cater to the learning styles of individuals with DS; 5) daily reminders to encourage regular practice and reinforce the importance of consistency; and 6) modified session structure to ensure that participants are able to discuss their experiences and refine their mindfulness practice. During the first 6 months of the project, the investigators will meet monthly with the community advisory board and use an iterative process to develop detailed intervention protocol for a virtual MBTI suitable for young people with DS. Aim 2 of the project will be to pilot test the efficacy of the virtual MBTI for young people with DS. In the second half of the one-year project, the investigators will conduct a pilot randomized clinical trial (RCT) of the intervention developed in Aim 1. This project will compare the effectiveness of Mindfulness Based Therapy for Insomnia (MBTI) and Brief Behavioral Therapy for Insomnia (BBTI) for young people with Down syndrome (DS). The interventions will be compared on their impact on improving sleep problems, quality of life, and functional outcomes. This project will also test if targeting the sleep of the caregiver in addition to the individual with Down syndrome has any effect on the outcomes.

This project studies the neurocognitive basis of trust adjustment in intellectual disability (ID), a source of significant vulnerability for these patients, focusing on two target populations chosen for their specific social characteristics: people with Down syndrome, who are often described as being hypersocial, and people with Fragile X syndrome, who are often characterized by a completely opposite social behaviour profile, with a withdrawn attitude and significant social anxiety. The three different types of mechanisms that contribute to the adjustment of interpersonal trust: affective evaluation, trait attribution, and epistemic evaluation of informants, will be studied. Affective evaluation processes recruit subcortical structures such as the amygdala and assess potential social threats in the environment. The second mechanism for selecting whom to trust consists of forming a representation of a person's dispositions, such as benevolence and competence (also known as traits), and using it to predict that person's future behaviour. Trait attribution processes recruit a cortico-cerebellar network comprising the mPFC, CRUS I and posterior lobule VI. The third mechanism, called epistemic vigilance, allows to adjust our trust in what others communicate to us. This mechanism involves linking the assessment of the reliability of individuals who communicate (based on their benevolence and competence) with the reliability of the communicated information. Epistemic assessment involves frontal areas and areas associated with the representation of mental states in order to enable the evaluation of the truthfulness of the communicated information. All of these mechanisms become functional very early on, before a child's sixth birthday. There are reasons to expect that several of these central mechanisms supporting selective trust will behave atypically in intellectual disability.

The purpose of this study is to evaluate whether levetiracetam can prevent epileptic seizures in patients with Alzheimer's disease associated with Down syndrome. It will also analyze whether it can delay the neurodegeneration associated with this disease. Patients will be randomly assigned to one of two groups: one group will receive the active drug (levetiracetam), and the other will receive a placebo. Both groups will receive the treatment for 96 weeks. Each patient will participate for a total of 2 years and 5 months.

The goal of this observational study is to evaluate the acceptability ofpatients with trisomy 21 (T21) to perform the full battery of ENDI neurospychological tests and each of the subsets. In this study, three types of population will be recruted : normotypic volunteers, patients with Intellectual Disability and patients T21carriers. This study is separated into 2 phases : * A the preliminary phase : this phase will be used to evaluate subtest design, ergonomics and understanding of instructions, and to identify any malfunctions. The observations gathered will enable the principal investigator to refine the digital design of the battery in collaboration with the publishing company. In this phase, normotypical volunteers and patients with intellectual disabilities will be recruted to perform ENDI test battery. * A main phase : this phase will enable to answer to the main objective. in this phase, patients with Trisomy 21 aged between 25 and 65 will be recruted to perform ENDI test battery.