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.     

Health care utilization and perceptions of health among adolescents and adults with Turner syndrome

We surveyed women aged 12 years and older who are members of the Turner Syndrome Society of the United States in regard to their health history, current health status, and health care utilization practices to identify the range of health problems and health care practices in this group. The mean age at diagnosis was 10.8 years, and an endocrinologist (41%) or pediatrician (35%) was most likely to make the initial diagnosis. Individuals over age 35 years were diagnosed with Turner syndrome and begun on estrogen replacement therapy at a significantly older age than those who were in younger age groups. Seventy-five percent of the respondents had required some type of surgical procedure, and 14% had been hospitalized within the previous year. Ninety-four percent of women rated their overall health as good to excellent, while 6% rated it fair to poor. In the 12–17-year age group, 89% of the young women were either currently taking or had previously taken growth hormone. The prevalence of major depressive symptoms was slightly higher than the general population for adolescents but similar to the general population for adults. For adult respondents, ratings of fair to poor health were significantly associated with increased outpatient visits. Growth hormone use was significantly associated with increased visits in the adolescent population. Based on these data, it appears that the clinical care of individuals with Turner syndrome has improved, but that they continue to have relatively high hospitalization rates and utilization of subspecialty services. Despite these health problems, most respondents demonstrated good adjustment as determined by standardized mental health measures.     

Practical guidelines for managing adults with 22q11.2 deletion syndrome

22q11.2 Deletion syndrome (22q11.2DS) is the most common microdeletion syndrome in humans, estimated to affect up to 1 in 2,000 live births. Major features of this multisystem condition include congenital anomalies, developmental delay, and an array of early- and later-onset medical and psychiatric disorders. Advances in pediatric care ensure a growing population of adults with 22q11.2DS. Informed by an international panel of multidisciplinary experts and a comprehensive review of the existing literature concerning adults, we present the first set of guidelines focused on managing the neuropsychiatric, endocrine, cardiovascular, reproductive, psychosocial, genetic counseling, and other issues that are the focus of attention in adults with 22q11.2DS. We propose practical strategies for the recognition, evaluation, surveillance, and management of the associated morbidities.Genet Med17 8, 599–609.     

Low adherence to national guidelines for thyroid screening in Down syndrome

PurposeTo determine adherence to the American Academy of Pediatrics guidelines for thyroid screening in children with Down syndrome among primary care providers in the states of Oklahoma and Nebraska.MethodsWe sought to identify all children with Down syndrome born in Oklahoma and Nebraska between 1994 and 2004 and review their medical records for evidence of thyroid screening. Patients were identified through a State Department of Health birth defects registry in Oklahoma and through participation in genetics clinics and laboratories in Nebraska and Oklahoma. Charts obtained from primary care providers were reviewed and the number of actual thyroid screens was compared with the number of recommended screens for each individual during the study period.ResultsIn Oklahoma, 13% of participating children received all thyroid screens recommended in the guidelines. In Nebraska, 14% of children received all recommended thyroid screenings. Among participants in Oklahoma, a mean of 34% of recommended thyroid screenings were performed. In Nebraska, a mean of 45% of recommended thyroid screenings were performed.ConclusionsThe level of adherence to the American Academy of Pediatrics guidelines for thyroid screening in children with Down syndrome is low. Factors contributing to this low level of adherence need to be identified and addressed.     

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.     

Oxygen uptake kinetics during exercise in adults with Down syndrome

Persons with Down syndrome (DS) have diminished submaximal and peak work capacity. This study evaluated the dynamic response of oxygen uptake at onset and recovery (VO₂ kinetics) of constant-load exercise (moderate intensity 45% VO_2peak) in adults with DS. A total of 27 healthy participants aged 18–50 years performed graded treadmill exercise to assess peak VO₂: 14 with DS (9 males and 5 females) and 13 controls without disabilities (9 males and 4 females). Subjects also performed constant-load exercise tests at 45% VO_2peak to determine VO₂ on-transient and VO₂ off-transient responses. Peak VO₂ was lower in participants with DS as compared to controls (DS 30.2 ± 7.1; controls 46.1 ± 9.6 mL kg⁻¹ min⁻¹, P < 0.05). In contrast, at 45% VO_2peak, the time constants for the VO₂ on-transients (DS 34.6 ± 9.1; controls 37.6 ± 9.0 s) and VO₂ off-transients (DS 36.5 ± 12.3; controls 37.7 ± 7.0 s) were not significantly different between the groups. Additionally, there were no differences between on-transient and off-transient time constants in participants with DS or controls. These data demonstrate that the VO₂ kinetics at onset and recovery of moderate intensity exercise is similar between adults with DS and controls. Therefore, the submaximal exercise performance of these individuals is not affected by slowed VO₂ kinetics.     

Frontal white matter integrity in adults with Down syndrome with and without dementia

Adults with Down syndrome (DS) are at high risk for developing Alzheimer's disease after the age of 40 years. To detect white matter (WM) changes in the brain linked to dementia, fractional anisotropy (FA) from diffusion tensor imaging was used. We hypothesized that adults with DS without dementia (DS n = 10), DS with dementia (DSAD n = 10) and age matched non-DS subjects (CTL n = 10) would show differential levels of FA and an association with scores from the Brief Praxis Test and the Severe Impairment Battery. WM integrity differences in DS compared with CTL were found predominantly in the frontal lobes. Across all DS adults, poorer Brief Praxis Test performance correlated with reduced FA in the corpus callosum as well as several association tracts, primarily within frontoparietal regions. Our results demonstrate significantly lower WM integrity in DS compared with controls, particularly in the frontal tracts. DS-related WM integrity reductions in a number of tracts were associated with poorer cognition. These preliminary results suggest that late myelinating frontal pathways may be vulnerable to aging in DS.     

Multimodal inhibition of return effects in adults with and without Down syndrome

Data from a previous study (Welsh & Elliott, 2001) has been reanalyzed to explore inhibition of return (IOR) effects in adults with and without Down syndrome (DS). Participants were required to react and move with either the left or right hand as quickly as possible to 1 of 2 target locations based on either a visual or a verbal cue. Although persons with DS demonstrated a different pattern of information processing capabilities, they demonstrated the same magnitude of IOR across all conditions of presentation as their peers without DS. This pattern of results provides further support for the multimodal and response-based nature of IOR. Moreover, the results indicate that the inhibitory processes that underlie IOR in the average population seem to be functional in persons with DS.     

Increased risk of symptomatic gallbladder disease in adults with Down syndrome

Previous reports have documented an increased prevalence of asymptomatic cholelithiasis among children with Down syndrome. Whether this predisposes adults with Down syndrome to symptomatic gallbladder disease has not been studied. A case control study compared the rate of symptomatic gallbladder disease in 28 index cases of adults with Down syndrome and that of sex-matched controls. The rate of gallbladder disease was 25% among the Down syndrome group, compared to 4.5% among the control group (P = 0.002). Patients with Down syndrome were also more likely to have a family medical history of gallbladder disease. Utilizing logistic regression analysis, the adjusted relative risk for gallbladder disease among individuals with Down syndrome was 3.52.     

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.     

Neurobehavioral disorders in children, adolescents, and young adults with Down syndrome

The term dual-diagnosis refers to a person with mental retardation and a psychiatric disorder. Most children with Down syndrome (DS) do not have a psychiatric or neurobehavioral disorder. Current prevalence estimates of neurobehavioral and psychiatric co-morbidity in children with DS range from 18% to 38%. We have found it useful to distinguish conditions with a pre-pubertal onset from those presenting in the post-pubertal period, as these are biologically distinct periods each with a unique vulnerability to specific psychiatric disorders. Due to the increased recognition that psychiatric symptoms may co-occur with mental retardation, and are not inextricably linked to cognitive impairment, these conditions are considered treatable, in part, under a medical model. Improvement in physiologic regulation, emotional stability, and neurocognitive processing is one of the most elusive but fundamental goals of pharmacologic intervention in these disorders.     

The mortality of adults with Down syndrome as a function of age

This study sought to test the hypothesis that adults with Down Syndrome may age faster than the general population by comparing the rate of increase in their mortality with age with that of the general population by the method originally described by Gompertz. The differences were not statistically significant. There is a striking difference in morbidity, the Down's adults being highly vulnerable. Alzheimer populations do not lend themselves readily to this type of analysis.     

Feedback reliance during an arm-tapping task with obstacle avoidance in adults with Down syndrome

Optimal movement control reflects a combination of both feedback and feedforward processes. However, as motor control evolves, feedforward mechanisms become prevailing respect to feedback-based movements, and less reliance on sensory information leads to a decreased number of corrections in the trajectory. In subjects with Down syndrome (DS), the study of the wrist’s trajectory during an arm-tapping task revealed feedback-based corrections designed to reduce the degree of discrepancy between the position of the limb and the target, leading to the assumption that performers with DS have problems with movement planning and feedforward control. The present study was aimed at expanding the evidence about motor control in DS by evaluating the influence of a perturbing factor (an obstacle) on motor control strategies during an arm-tapping task and to clarify if the presence of an obstacle elicited a higher reliance on feedback control in controls and in DS. Sixteen right-handed adults with DS and 21 right-handed, age-matched control subjects (N) were evaluated by means of quantitative motion analysis. The results suggest that the presence of an obstacle elicited changes in the motor strategies of both DS and N, with a destabilizing effect that led subjects to rely more on feedback control. DS showed some aspects of movement efficiency that were in accordance with N strategies, but the prevailing factor of optimization in these subjects remained safety. A focused rehabilitation could help DS subjects to develop more efficient motor strategies in the presence of motor uncertainty and perturbations.     

Personalized medicine for individuals with Down syndrome

As the cost of whole genome analysis decreases, we have the opportunity to explore the interactions of various gene changes in an individual that lead to their particular phenotype. This will provide the ability to move from the epidemiologic study of groups, in which, the individuals are treated collectively and homogenously, to personalized medicine, and a model in which the individual is recognized and treated as a distinct entity. We will be applying personalized medicine to individuals with Down syndrome in order to understand and develop biomarkers for increased risk of co-morbidities. Personalized medicine will change the "culture of intractability" of Down syndrome.