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Aging Cell Jun 2019Down syndrome (DS) has been proposed by George Martin as a segmental progeroid syndrome since 1978. In fact, DS persons suffer from several age-associated disorders much... (Review)
Review
Down syndrome (DS) has been proposed by George Martin as a segmental progeroid syndrome since 1978. In fact, DS persons suffer from several age-associated disorders much earlier than euploid persons. Furthermore, a series of recent studies have found that DS persons display elevated levels of age biomarkers, thus supporting the notion that DS is a progeroid trait. Nowadays, due to the progressive advancements in social inclusion processes and medical assistance, DS persons live much longer than in the past; therefore, the early-onset health problems of these persons are becoming an urgent and largely unmet social and medical burden. In particular, the most important ailment of DS persons is the accelerated cognitive decline that starts when they reach about 40 years of age. This decline can be at least in part counteracted by multi-systemic approaches including early-onset cognitive training, physical activity, and psychosocial assistance. However, no pharmacological treatment is approved to counteract this decline. According to the most advanced conceptualization of Geroscience, tackling the molecular mechanisms underpinning the aging process should be a smart/feasible strategy to combat and/or delay the great majority of age-related diseases, including cognitive decline. We think that a debate is needed urgently on if (and how) this strategy could be integrated in protocols to face DS-associated dementia and overall unhealthy aging. In particular we propose that, on the basis of data obtained in different clinical settings, metformin is a promising candidate that could be exploited to counteract cognitive decline in DS.
Topics: Animals; Cognitive Aging; Down Syndrome; Humans
PubMed: 30768754
DOI: 10.1111/acel.12903 -
Journal of Assisted Reproduction and... Jul 2022The use of assisted reproductive technology (ART) and prenatal genetic testing have become more widespread in line with an increase in maternal age. However, the effect...
PURPOSE
The use of assisted reproductive technology (ART) and prenatal genetic testing have become more widespread in line with an increase in maternal age. However, the effect of the introduction of non-invasive prenatal testing (NIPT) in April 2013 on pregnancy outcomes in Japan, including the prevalence of Down syndrome live births following ART, has not been investigated. This study aimed to evaluate the trends in the prevalence of Down syndrome live births following ART in Japan.
METHODS
This population-based retrospective study used the Japanese nationwide ART registry. All clinical pregnancies resulting in live births, stillbirths, and termination of pregnancy (TOP) following ART from 2007 to 2016 were included. Pregnancy outcomes involving infants with Down syndrome were evaluated.
RESULTS
Among 351,808 pregnancies, the proportion of mothers with advanced age increased significantly from 2007 to 2016 (from 49.5 to 62.4% and 8.9 to 17.8% for mothers aged ≥ 35 and ≥ 40 years, respectively). The proportion of live births with Down syndrome was 77.3% in 2007, which remained consistent until 2012, but then decreased significantly to 45.1% after 2013 (P < 0.001). The prevalence of Down syndrome live births increased up to 2012 (19.5/10,000 live births), decreased significantly in 2013 (12.1/10,000 live births), and then remained almost stable (11.1-14.7/10,000 live births).
CONCLUSION
The introduction of NIPT balanced the prevalence of Down syndrome live births following ART with recent increasing maternal age in Japan.
Topics: Down Syndrome; Female; Humans; Infant; Japan; Live Birth; Pregnancy; Reproductive Techniques, Assisted; Retrospective Studies
PubMed: 35597856
DOI: 10.1007/s10815-022-02501-4 -
Journal of the American Board of Family... 2020To describe demographic factors and calculate prevalence of heart disease-related conditions among the adult Down syndrome (DS) sample population and to compare...
PURPOSE
To describe demographic factors and calculate prevalence of heart disease-related conditions among the adult Down syndrome (DS) sample population and to compare demographic and heart disease-related conditions between the DS sample population (n = 2342) and the general population.
METHODS
Using a retrospective, descriptive cohort study design, analyses were based on 20 years of data collected on the Adult Down Syndrome Center patient population. Prevalence of heart disease, stroke, and associated risk conditions are reported as counts (%) with corresponding odds ratio (OR) indicating odds of diagnosis among the DS sample compared with the general population. Corresponding Pearson c-values were calculated to represent statistically significant differences between prevalence of diagnoses in the DS sample compared with the general population. In cases where prevalence was low, Fisher's Exact Test -value were calculated.
RESULTS
Adults with DS had lower odds of diagnosis of heart disease and most associated risk conditions, specifically coronary heart disease (OR = 0.0537, .0001), heart failure (OR = 0.6353, .0091), hypertension (OR = 0.0325, .0001), diabetes (OR = 0.4840, .0001), and high total cholesterol (OR = 0.2086, .0001), while experiencing higher odds of overweight status (OR = 1.2185, .0002) and obese status (OR = 1.3238, .0001).
CONCLUSION
Adults with DS generally experience less heart disease and associated risk conditions commonly seen in the general population. Prevention and treatment guidelines for heart disease for the DS population should be adjusted after more research is conducted.
Topics: Adult; Cohort Studies; Down Syndrome; Heart Diseases; Humans; Prevalence; Retrospective Studies
PubMed: 33219071
DOI: 10.3122/jabfm.2020.06.190425 -
Reviews in the Neurosciences Jun 2023Down syndrome (DS), a genetic pathology caused by triplication of chromosome 21, is characterized by brain hypotrophy and impairment of cognition starting from infancy.... (Review)
Review
Down syndrome (DS), a genetic pathology caused by triplication of chromosome 21, is characterized by brain hypotrophy and impairment of cognition starting from infancy. While studies in mouse models of DS have elucidated the major neuroanatomical and neurochemical defects of DS, comparatively fewer investigations have focused on the electrophysiology of the DS brain. Electrical activity is at the basis of brain functioning. Therefore, knowledge of the way in which brain circuits operate in DS is fundamental to understand the causes of behavioral impairment and devise targeted interventions. This review summarizes the state of the art regarding the electrical properties of the DS brain, starting from individual neurons and culminating in signal processing in whole neuronal networks. The reported evidence derives from mouse models of DS and from brain tissues and neurons derived from individuals with DS. EEG data recorded in individuals with DS are also provided as a key tool to understand the impact of brain circuit alterations on global brain activity.
Topics: Mice; Animals; Humans; Down Syndrome; Neurons; Brain; Cognition; Disease Models, Animal; Neural Networks, Computer
PubMed: 36170842
DOI: 10.1515/revneuro-2022-0067 -
JNMA; Journal of the Nepal Medical... Aug 2023Down syndrome is the most common chromosomal abnormality among liveborn infants that frequently causes intellectual disability. However, with proper medical care and...
UNLABELLED
Down syndrome is the most common chromosomal abnormality among liveborn infants that frequently causes intellectual disability. However, with proper medical care and support, children with Down syndrome can still lead fulfilling lives and achieve their full potential. The experience at Satyam Day Care Center has provided valuable insights into the challenges and opportunities of caring for children with Down syndrome. Advocating for increased awareness and understanding of Down syndrome, including its genetic causes, associated health conditions, and developmental delays is important.
KEYWORDS
developmental disabilities; Down syndrome; holistic health; medical student.
Topics: Child; Infant; Humans; Down Syndrome; Students, Medical; Intellectual Disability
PubMed: 38289810
DOI: 10.31729/jnma.8244 -
British Journal of Haematology Aug 2018
Topics: Adult; Down Syndrome; Female; Humans; Precursor Cell Lymphoblastic Leukemia-Lymphoma
PubMed: 29741756
DOI: 10.1111/bjh.15264 -
Research in Developmental Disabilities Jul 2022Specific medical conditions are more prevalent in Down syndrome (DS) compared to the general population. Medical heterogeneity has also been hypothesized to contribute...
BACKGROUND
Specific medical conditions are more prevalent in Down syndrome (DS) compared to the general population. Medical heterogeneity has also been hypothesized to contribute to variability in outcomes in DS.
AIMS
This project aimed to examine the association between medical conditions (i.e., gastrointestinal issues, hearing loss, vision problems, and congenital heart defects) and cognition, language, and behavior in children and adolescents with DS.
METHODS AND PROCEDURES
Participants were 73 children and adolescents with DS, ages 6-17 years (M = 12.67, SD = 3.16). Caregivers reported on participants' medical conditions, social behaviors, maladaptive behaviors, and executive function. Child cognitive abilities were also assessed.
OUTCOMES AND RESULTS
Of the 73 participants, 34.2% had gastrointestinal issues, 12.3% had uncorrected hearing loss, 26.0% had uncorrected vision problems, and 31.5% had congenital heart defects. Participants with gastrointestinal issues had significantly more challenges with social behaviors, maladaptive behaviors, and executive function compared to those without gastrointestinal issues.
CONCLUSIONS AND IMPLICATIONS
The associations identified between gastrointestinal issues and caregiver-reported behavioral characteristics in youth with DS contributes to our understanding of the interrelation between co-occurring medical conditions and child outcomes and has implications for approaches to care for individuals with DS.
Topics: Adolescent; Child; Cognition; Down Syndrome; Executive Function; Heart Defects, Congenital; Humans; Language
PubMed: 35468571
DOI: 10.1016/j.ridd.2022.104236 -
Journal of Autism and Developmental... Feb 2020Previous studies suggest that tasks dependent on the mental number line may be difficult for Williams Syndrome (WS) and Down Syndrome (DS) groups. However, few have...
Previous studies suggest that tasks dependent on the mental number line may be difficult for Williams Syndrome (WS) and Down Syndrome (DS) groups. However, few have directly assessed number line estimation in these groups. The current study assessed 28 WS, 25 DS and 25 typically developing (TD) participants in non-verbal intelligence, number familiarity, visuo-spatial skills and number line estimation. Group comparisons indicated no differences in number line estimation. However, the WS group displayed difficulties with visuo-spatial skills and the DS group displayed difficulties with number familiarity. Differential relationships between number line estimation and visuo-spatial/number familiarity skills were observed across groups. Data is discussed in the context of assessment of skills in neurodevelopmental disorders.
Topics: Adolescent; Adult; Child; Comprehension; Down Syndrome; Female; Humans; Intelligence; Male; Mathematical Concepts; Middle Aged; Psychomotor Performance; Williams Syndrome; Young Adult
PubMed: 31705420
DOI: 10.1007/s10803-019-04268-7 -
Progress in Brain Research 2020The presence of an extra copy of human chromosome 21 (Hsa21) leads to a constellation of phenotypic manifestations in Down syndrome (DS), including prominent effects on... (Review)
Review
The presence of an extra copy of human chromosome 21 (Hsa21) leads to a constellation of phenotypic manifestations in Down syndrome (DS), including prominent effects on the brain and immune system. Intensive efforts to unravel the molecular mechanisms underlying these phenotypes may help developing effective therapies, both in DS and in the general population. Here we review recent progress in genetic and epigenetic analysis of trisomy 21 (Ts21). New mouse models of DS based on syntenic conservation of segments of the mouse and human chromosomes are starting to clarify the contributions of chromosomal subregions and orthologous genes to specific phenotypes in DS. The expression of genes on Hsa21 is regulated by epigenetic mechanisms, and with recent findings of highly recurrent gene-specific changes in DNA methylation patterns in brain and immune system cells with Ts21, the epigenomics of DS has become an active research area. Here we highlight the value of combining human studies with mouse models for defining DS critical genes and understanding the trans-acting effects of a simple chromosomal aneuploidy on genome-wide epigenetic patterning. These genetic and epigenetic studies are starting to uncover fundamental biological mechanisms, leading to insights that may soon become therapeutically relevant.
Topics: Aging, Premature; Animals; Cerebral Cortex; Disease Models, Animal; Down Syndrome; Epigenesis, Genetic; Humans; Mice
PubMed: 32057305
DOI: 10.1016/bs.pbr.2019.09.002 -
Journal of Clinical Hypertension... Jul 2020The paradigmatic relationship between aging and atherosclerotic cardiovascular events does not apply to all patient populations. Though trisomy 21 (T21) and its... (Review)
Review
The paradigmatic relationship between aging and atherosclerotic cardiovascular events does not apply to all patient populations. Though trisomy 21 (T21) and its phenotypic expression, Down syndrome (DS), are conditions that involve premature aging, the cardiovascular system of adults with DS appears to be particularly spared from this early senescence. Despite a higher prevalence of some classic cardiovascular risk factors in adults with DS than in the general population, such as dyslipidemia, obesity, or sedentarism, these individuals do not develop hypertension or suffer major cardiovascular events as they age. The protective factors that prevent the development of hypertension in T21 are not well established. Genes like RCAN1 and DYRK1A, both on chromosome 21 and over-expressed in adults with DS, appear to play a major role in cardiovascular prevention. Their regulation of the renin-angiotensin-aldosterone system (RAAS) and neprilysin synthesis could underlie the constitutive protection against arterial hypertension in adults with DS and explain the absence of increased arterial stiffness in this population. A better understanding of these molecular pathways could have enormous implications for the clinical management of adults with DS and might foster the development of novel therapeutic targets in cardiovascular prevention for the general population.
Topics: Adult; Aging; DNA-Binding Proteins; Down Syndrome; Humans; Hypertension; Muscle Proteins; Renin-Angiotensin System; Vascular Stiffness
PubMed: 32644285
DOI: 10.1111/jch.13930