Cardiometabolic risk in young adults with Down syndrome

Studies regarding cardiometabolic risk (CMR) for individuals with Down syndrome (DS) conflict. Our previous research in youth with DS, aged 10–20 years, found increased prevalence of dyslipidemia and prediabetes compared to matched peers without DS. Herein, we compare CMR in young adults with DS, aged 18–35 years, to a similar population-based sample from the 2001–2018 National Health and Nutrition Examination Survey (NHANES). The group with DS had higher NonHDL-C (mean DS 131.9 mg/dL; NHANES 126.1 p < 0.001), lower HDL-C (DS 47.5 mg/dL; NHANES 52.2 p < 0.001), higher LDL-C (DS 109.3 mg/dL; NHANES 105.4 p < 0.001), higher triglycerides (DS 102.9 mg/dL; NHANES 86.9 p < 0.001), but lower fasting glucose (DS 85.8 mg/dL; NHANES 95.2 p < 0.0001), lower HOMA-IR (DS 2.17; NHANES 2.24 p = 0.0006), lower systolic (DS 109.7 mmHg; NHANES 114.6 p < 0.0001) and lower diastolic (DS 60.9 mmHg; NHANES 67.8 p < 0.0001) blood pressures. There was relationship of higher HDL-C, triglycerides, glucose, systolic, and diastolic blood pressure with increasing BMI in the NHANES cohort which was dampened in the group with DS. These results indicate that more information is needed to guide clinicians in screening for CMR in individuals with DS.     

Walking economy in male adults with Down syndrome

The purpose of this study was to investigate walking economy in response to steady-state locomotion in adult males with Down syndrome (DS) and in healthy controls. Twelve participants with DS (34.5 ± 7.0 years) and 11 non-disabled controls (34.3 ± 8.7 years) performed submaximal (0% grade, 2.5 km h⁻¹ for 8 min) and maximal treadmill tests with metabolic and heart-rate measurements. For submaximal walking, submaximal oxygen uptake (VO₂) (9.1 vs. 9.5 mL kg⁻¹ min⁻¹), net VO₂ (5.9 vs. 5.4 mL kg⁻¹ min⁻¹) were not different between the groups (P > 0.05). However, oxygen-pulse (6.6 vs. 8.6 mL/beat) was lower and relative work intensity (44.6 vs. 19.9% of max) was higher in individuals with DS compared to controls (P < 0.05). Findings indicate similar walking economy between groups. Nevertheless, participants with DS exercised at lower submaximal oxygen-pulse and higher percentage of VO_2peak. Therefore, despite similar walking economy, participants with DS have lower cardiorespiratory function than controls for a given steady-state treadmill speed.     

SARS-CoV-2 vaccine humoral response in adults with Down syndrome

ObjectivePeople with Down syndrome (DS) are particularly vulnerable to coronavirus disease 2019 (COVID-19) and show altered immune response to vaccination. We aimed to evaluate the immune response of a group of adults with DS treated with standard regimens of SARS-CoV-2 vaccine as compared with an age- and sex-matched group of persons without DS.MethodsWe compared antibody responses between 42 subjects with DS (41.6 ± 10.8 years, 57% male), and an age- and sex-matched comparison group of healthy health care workers (HCW) (41.4 ± 8.8 years, 54.8% male) after SARS-CoV-2 vaccination with the standard regimen of BNT162b2 mRNA COVID-19. Receptor binding domain (RBD) IgG antibodies were assessed at 4 time points (baseline, 21 days after the first dose, 21 days after the second dose, and 6 months after the first dose) with Siemens SARS-CoV-2 IgG (COV2G) antibody test.ResultsWe observed significantly different antibody responses at all time points after vaccination (HCW vs. DS: 7.9 ± 3.9 vs. 1.4 ± 3.6 IU/mL at 21 days after first dose; 358.5 ± 3.8 vs. 38.1 ± 3.0 IU/mL at 21 days after second dose; 34.6 ± 2.4 vs. 7.9 ± 3.1 IU/mL at 6 months after vaccination) and a significantly different time course of decline in antibody titers between the two groups.DiscussionSubjects with DS have a valid antibody response to SARS-CoV-2 vaccination. However, this response is lower than that of subjects in the HCW group. This finding could indicate a more rapid decline in the protective effects of the vaccination in subjects with DS and could suggest that people with DS may benefit from a booster dose of vaccine.     

Cholesterol level, statin use and Alzheimer's disease in adults with Down syndrome

Adults with Down syndrome (DS) are at significantly higher risk of Alzheimer's disease (AD) than the general population, but there is considerable variability in age at onset. This study tested the hypothesis that total cholesterol (TC) levels are related to vulnerability, and that the use of statins may decrease risk. The relation of TC level and statin use to risk of AD was investigated in 123 Caucasian adults with DS. Evaluations included serial assessments of cognitive, adaptive and maladaptive behavior, medical records, and neurological examinations. Mean length of follow-up was 5.5 years [1.2-7.1] for the entire sample, 5.1 years [1.2-7.1] for subjects who developed dementia, and 5.6 years [1.5-7.1] for those who did not develop dementia. Controlling for covariates, participants with TC>or=200mg/dL were more than two times as likely to develop AD than subjects with lower TC [hazard rate (HR)=2.59, p=.029, 95% CI: 1.1, 6.1]. In contrast, participants with higher TC levels who used statins during the study, had less than half the risk of developing AD than participants with higher TC levels who did not use statins (HR=.402, p=.095, 95% CI: .138, 1.173). If the protective effects of statins can be further validated, these findings suggest that their use may delay or prevent AD onset in vulnerable populations.     

Event-related potential index of age-related differences in memory processes in adults with Down syndrome

A major goal of aging research is to identify early markers of age-related cognitive decline. Persons with Down syndrome (DS) experience accelerated aging and high risks for dementia, making them a valuable albeit understudied model for testing such markers. This study examined event-related potential (ERP) indices of visual memory in younger (19–25 years) and older (35–40 years) adults with DS using a passive viewing paradigm that did not require memorization or behavioral responses. ERPs were recorded in response to unfamiliar urban and nature scenes, with some images presented once and others repeated multiple times. Within 600 to 900 milliseconds after stimulus onset, repeated stimuli elicited more positive amplitudes in younger participants, indicating stimilus recognition. ERPs of older adults did not show such increases, suggesting reduced memory functioning. ERP indices were unrelated to participants' intellectual functioning, but did correlate with age and caregiver-reported lethargy/withdrawal behaviors. Passive ERP measures of memory processes are sensitive to early stages of cognitive decline in DS and are promising markers of cognitive risk for future aging studies.     

The burden of chronic disease,multimorbidity, and polypharmacy in adults with Down syndrome

Data on clinical characteristics of adults with Down syndrome (DS) are limited and the clinical phenotype of these persons is poorly described. This study aimed to describe the occurrence of chronic diseases and pattern of medication use in a population of adults with DS. Participants were 421 community dwelling adults with DS, aged 18 years or older. Individuals were assessed through a standardized clinical protocol. Multimorbidity was defined as the occurrence of two or more chronic conditions and polypharmacy as the concomitant use of five or more medications. The mean age of study participants was 38.3 ± 12.8 years and 214 (51%) were women. Three hundred and seventy‐four participants (88.8%) presented with multimorbidity. The most prevalent condition was visual impairment (72.9%), followed by thyroid disease (50.1%) and hearing impairment (26.8%). Chronic diseases were more prevalent among participants aged >40 years. The mean number of medications used was 2.09 and polypharmacy was observed in 10.5% of the study sample. Psychotropic medications were used by a mean of 0.7 individuals of the total sample. The high prevalence of multimorbidity and the common use of multiple medications contributes to a high level of clinical complexity, which appears to be similar to the degree of complexity of the older non‐trisomic population. A comprehensive and holistic approach, commonly adopted in geriatric medicine, may provide the most appropriate care to persons with DS as they grow into adulthood.     

Non-invasive estimation of afferent inputs for postural stability under low levels of alcohol

The maintenance of human equilibrium is a complex process. Several physiological systems provide afferent information for postural stabilization. This study describes a noninvasive methodology to estimate the relative roles of interacting afferent inputs relevant for postural control. A multiaxis force platform in conjunction with specially designed test procedure provided semi-quantitative insight into the roles of vision, proprioceptors and vestibular apparatus in controlling postural sway when it was perturbed by a central nervous system perturbator such as alcohol. Experiments were conducted on 10 male and 10 female subjects. The males did not show statistically significant increases in body sway at these low levels of alcohol. For the females, the present methodology could detect subtle changes in postural sway at low blood alcohol levels ranging between 0.015% and 0.03%. At these low levels of alcohol, the results from females show that when the vision was excluded and the proprioception was modified, the postural sway was most affected. The postural instability experienced in this condition is probably due to inappropriate responses to proprioceptive inputs and lack of vision. Both male and female subjects showed a strong “eyes by standing surface” interaction. The proprioceptor manipulation alone did not affect the postural stability.     

Micronucleated lymphocytes in parents of Down syndrome children

Down syndrome (DS) is the most common disease due to an autosomal aneuploidy in live born children and also the major known genetic cause of mental retardation. The risk of a DS pregnancy increases substantially with increasing maternal age. However, several women aged less than 35 years at conception have a child with DS. The micronucleus (MN) assay can identify chromosome breakage or chromosome malsegregation and is an ideal biomarker to investigate genomic instability. The aim of the present study was to determine the frequency of peripheral lymphocytes with MN in the parents of DS individuals. The subjects were 17 couples, 1 father and 9 mothers, and 24 couples who had at least one healthy child formed the control group. For each individual we evaluated the frequency of binucleated micronucleated lymphocytes (BNMN%) as number of binucleated lymphocytes containing one or more MN per 1000 binucleated cells. The mean age of DS parents and controls was 32.6 and 29.8 years, respectively. The frequency of MN in DS parents was significantly higher compared to controls. The higher frequency of MN in DS parents suggests a higher predisposition of DS parents to aneuploidy events in this sample.     

Parity and Down syndrome

Previous studies have suggested a positive correlation between grand multiparity and the incidence of Down syndrome (DS). In order to study different parities as risk factors for DS, the Swedish health registries were used, and 2,615 infants with Down syndrome were selected from 2,184,590 infants born in 1973–1993. A statistically significant risk decrease for primiparas, and a significant risk increase for grand multiparas (5+), was found (age-adjusted odds ratios: 0.87 (95% CI: 0.80–0.96) and 1.40 (95% CI: 1.18–1.65)), respectively. Potential confounders, such as the effect of truncated maternal 1-year age classes, citizenship, socioeconomic level, etc., were evaluated but were found to have only marginal effects. Evidence suggesting that the extension of prenatal diagnosis during the study period has decreased the incidence of DS among women of parity 1–4, but not among women of parity 5+, was found. The hypothesis that Swedish grand multiparas may have another attitude toward prenatal diagnosis than women of lower parities was confirmed when, in a data set containing information on 872 amniocenteses, a significantly lower rate of grand multiparity than expected was found. For the negative association between primiparity and DS, no obvious confounder was found. Am. J. Med. Genet. 70:196–201, 1997. © 1997 Wiley-Liss, Inc.     

Multijoint dynamics and postural stability of the human arm

The goal of this study was to examine how the mechanical properties of the human arm are modulated during isometric force regulation tasks. Specifically, we examined whether the dynamic stability of the limb remained nearly invariant across a range of voluntarily generated endpoint forces and limb postures. Previous single joint studies have demonstrated that dynamic joint stability, as quantified via estimates of the joint damping ratio, is nearly invariant during isometric torque regulation tasks. However, the relevance of these findings to the control of multijoint posture has not been investigated previously. A similar degree of invariance at the multijoint level could suggest a fundamental property of the motor system that could be incorporated into the planning and execution of multijoint tasks. In this work, limb mechanics were quantified using estimates of dynamic endpoint stiffness, which characterizes the relationship between imposed displacements of limb posture and the forces opposing those displacements. Endpoint stiffness was estimated using a two-link robot operating in the horizontal plane at the height of each subjects glenohumeral joint. The robot was used to apply stochastic position perturbations to the arm and to measure the resulting forces. Endpoint stiffness dynamics were estimated nonparametrically and subsequently summarized using inertial, viscous and elastic parameters. We found that in the tasks studied, there was a differential modulation of endpoint elasticity and endpoint viscosity. Elasticity increased nearly linearly with increases in voluntary force generation while viscosity increased nonlinearly. This differential regulation resulted in limb dynamics that had a remarkably consistent damping ratio across all subjects and all tested conditions. These results emphasize the importance of considering the full dynamic response of a limb when investigating multijoint stability, and suggest that a minimal degree of limb stability is maintained over a wide range of force regulation tasks.This work was supported by the Department of Veteran Affairs Rehabilitation Research and Development Service, the National Institute of Health, and the Cleveland FES Institute     

Caries in Portuguese children with Down syndrome

OBJECTIVES:

Oral health in Down syndrome children has some peculiar aspects that must be considered in the follow-up of these patients. This study focuses on characterizing the environmental and host factors associated with dental caries in Portuguese children with and without Down syndrome.

METHODS:

A sibling-matched, population-based, cross-sectional survey was performed.

RESULTS:

Down syndrome children presented a significantly greater percentage of children without caries, 78% vs. 58% of non-Down syndrome siblings. This difference in the DMFT index (number of decayed, missing and filled teeth) essentially reflects data obtained from treated teeth, for which 91% of children with Down syndrome had never had a tooth treated vs. 67% of siblings. This result was statistically significant, whereas results for decayed and lost teeth did not differ between Down syndrome children and their unaffected siblings. Additionally, in Down syndrome children, a delayed eruption of the second molar occurs. Down syndrome children and their siblings have similar oral hygiene habits, but a higher percentage of Down syndrome children visit a dentist before the age of three years, in comparison to their siblings. Bruxism was also more common in Down syndrome children compared to their siblings.

CONCLUSIONS:

Our results show that Portuguese children with Down syndrome have lower caries rates than children without Down syndrome. This reduced prevalence may be associated with the parents'' greater concern about oral health care in Down syndrome children, resulting in their taking them sooner to visit a dentist, as well as to a higher bruxism prevalence and delayed tooth eruption.     

Gastrointestinal disorders in Down syndrome

Down syndrome is the most common human chromosomal disorder. Among clinical findings, one constant concern is the high prevalence of gastrointestinal system alterations. The aim of this study was to determine the prevalence of gastrointestinal disorders at a Down syndrome outpatient clinic during a 10‐year follow‐up period. Data from medical files were retrospectively reviewed from 1,207 patients. Gastrointestinal changes occurred in 612 (50.7%). The most prevalent disorder was chronic intestinal constipation. Intestinal parasite occurred in 22% (mainly giardiasis), gastroesophageal reflux disease in 14%, digestive tract malformations occurred in 5%: 13 cases of duodenal atresia, 8 of imperforate anus, 4 annular pancreases, 2 congenital megacolon, 2 esophageal atresias, 2 esophageal compression by anomalous subclavian and 1 case of duodenal membrane. We had 38/1,207 (3.1%) patients with difficulty in sucking and only three with dysphagia that resolved before the second year of life. Peptic ulcer disease, celiac disease, and biliary lithiasis were less prevalent with 3% each. Awareness of the high prevalence of gastrointestinal disorders promotes outstanding clinical follow‐up as well as adequate development and greater quality of life for patients with Down syndrome and their families.     

Rapid clinical deterioration in an individual with Down syndrome

A small percentage of adolescents and young adults with Down syndrome experience a rapid and unexplained deterioration in cognitive, adaptive, and behavioral functioning. Currently, there is no standardized work‐up available to evaluate these patients or treat them. Their decline typically involves intellectual deterioration, a loss of skills of daily living, and prominent behavioral changes. Certain cases follow significant life events such as completion of secondary school with friends who proceed on to college or employment beyond the individual with DS. Others develop this condition seemingly unprovoked. Increased attention in the medical community to clinical deterioration in adolescents and young adults with Down syndrome could provide a framework for improved diagnosis, evaluation, and treatment. This report presents a young adult male with Down syndrome who experienced severe and unexplained clinical deterioration, highlighting specific challenges in the systematic evaluation and treatment of these patients. © 2016 Wiley Periodicals, Inc.

     

Hematopoietic disorders in Down syndrome

Patients with Down syndrome have an increased risk of developing various hematological disorders. In this article, the clinical characteristics and differential diagnosis of the hematological disorders associated with Down syndrome are reviewed, and the underlying molecular mechanisms discussed.     

Genetic diagnosis of Down syndrome in an underserved community

It is a matter of course that in high‐income countries, infants born with features suggestive of Down syndrome (DS) are offered genetic testing for confirmation of a clinical diagnosis. Benefits of a definitive diagnosis include an end to the diagnostic odyssey, informed prognosis, opportunities for caregiver support, inclusion to social support networks, and more meaningful genetic counseling. The healthcare experience for families of children born with DS in low‐ and middle‐income nations is in stark contrast with such a level of care. Barriers to obtaining genetic diagnosis might include economic disparities, geographical isolation, and lack of access to health care professionals trained in genetic medicine. As part of a combined research and community outreach effort, we provided genetic testing for several patients with DS. These individuals and their families live on several resource‐limited Caribbean islands and have either limited or virtually no access to medical genetics services. Within this group were three families with recurrent DS. Karyotype established that translocation events were not involved in the DS in any of these families. This information enabled genetic counseling to help family members understand their recurrent DS. A definitive diagnosis of DS is beneficial to families in resource‐limited communities and may help to provide such families with genetic counseling, reassurance, and peace of mind.

     

Salivary testosterone and immunoglobulin A were increased by resistance training in adults with Down syndrome

This study was designed to assess the influence of resistance training on salivary immunoglobulin A (IgA) levels and hormone profile in sedentary adults with Down syndrome (DS). A total of 40 male adults with DS were recruited for the trial through different community support groups for people with intellectual disabilities. All participants had medical approval for participation in physical activity. Twenty-four adults were randomly assigned to perform resistance training in a circuit with six stations, 3 days per week for 12 weeks. Training intensity was based on functioning in the eight-repetition maximum (8RM) test for each exercise. The control group included 16 age-, gender-, and BMI-matched adults with DS. Salivary IgA, testosterone, and cortisol levels were measured by ELISA. Work task performance was assessed using the repetitive weighted-box-stacking test. Resistance training significantly increased salivary IgA concentration (P=0.0120; d=0.94) and testosterone levels (P=0.0088; d=1.57) in the exercising group. Furthermore, it also improved work task performance. No changes were seen in the controls who had not exercised. In conclusion, a short-term resistance training protocol improved mucosal immunity response as well as salivary testosterone levels in sedentary adults with DS.     

The influence of stationary auditory fields on postural sway behaviour in man

Summary Postural sway behaviour was investigated in 30 young subjects (15 male and 15 female) during 60 s of erect standing, under various combinations of auditory and visual input. Sway was assessed using a standard biomechanical measuring platform, the output of which led directly to an online computer from which the following parameters were determined: mean lateral and antero-posterior sway, velocity and radius of sway, length of the sway path and area within the sway profile. A marked difference in sway behaviour between the sexes was observed, with women showing increased magnitudes of some sway parameters. Postural sway was significantly increased in conditions without visual feedback. The presence of an auditory field tends to have a destabilising influence on sway behaviour, with both the direction of the sound source and the type of auditory input being important variables. Nevertheless there appears to be no interaction between the visual and the auditory environment in the control of posture.