Search

Objectives: Characterise the circumstances associated with death during admission of adults with Down syndrome (DS) and to identify predictors of mortality., Patients and Methods: Observational study based on data on all emergent admissions of adults with DS to hospitals of the Spanish National Health System between 1997 and 2014. We analysed epidemiological and clinical variables., Results: We analysed admissions of 11,594 adults with DS, mean age 47 years. 1715 patients died (15%), being the highest mortality (35%) in individuals aged 50-59. A past medical history of cerebrovascular disease (aOR 2.95 [2.30-3.77]) or cancer (aOR 2.79 [2.07-3.75]), gross aspiration's admission (aOR 2.59 [2.20-3.04]), immobility (aOR 2.31 [1.46-3-62]), and readmission within 30 days (aOR 2.43 [2.06-2.86]) were identified as predictors of mortality., Conclusions: Adults with DS have a high in-hospital mortality rate. The main predictors of death were cerebrovascular disease, cancer, early readmission, and conditions commonly associated with advanced dementia., (© 2023 John Wiley & Sons Ltd.)

Objective: Alzheimer's disease (AD) is a major health concern for aging adults with Down syndrome (DS), but conventional diagnostic techniques are less reliable in those with severe baseline disability. Likewise, acquisition of magnetic resonance imaging to evaluate cerebral atrophy is not straightforward, as prolonged scanning times are less tolerated in this population. Computed tomography (CT) scans can be obtained faster, but poor contrast resolution limits its function for morphometric analysis. We implemented an automated analysis of CT scans to characterize differences across dementia stages in a cross-sectional study of an adult DS cohort., Methods: CT scans of 98 individuals were analyzed using an automatic algorithm. Voxel-based correlations with clinical dementia stages and AD plasma biomarkers (phosphorylated tau-181 and neurofilament light chain) were identified, and their dysconnectomic patterns delineated., Results: Dementia severity was negatively correlated with gray (GM) and white matter (WM) volumes in temporal lobe regions, including parahippocampal gyri. Dysconnectome analysis revealed an association between WM loss and temporal lobe GM volume reduction. AD biomarkers were negatively associated with GM volume in hippocampal and cingulate gyri., Interpretation: Our automated algorithm and novel dysconnectomic analysis of CT scans successfully described brain morphometric differences related to AD in adults with DS, providing a new avenue for neuroimaging analysis in populations for whom magnetic resonance imaging is difficult to obtain., (© 2023 The Authors. Annals of Clinical and Translational Neurology published by Wiley Periodicals LLC on behalf of American Neurological Association.)

Background: Immune dysregulation in individuals with Down syndrome (DS) leads to an increased risk for hospitalization and death due to coronavirus disease 2019 (COVID-19) and may impair the generation of protective immunity after vaccine administration., Methods: The cellular and humoral responses of 55 individuals with DS who received a complete SARS-CoV-2 vaccination regime at 1 to 3 (visit [V 1]) and 6 (V2) months were characterized., Results: SARS-CoV-2-reactive CD4+ and CD8+ T lymphocytes with a predominant Th1 phenotype were observed at V1 and increased at V2. Likewise, an increase in SARS-CoV-2-specific circulating Tfh (cTfh) cells and CD8+ CXCR5+ PD-1hi lymphocytes was already observed at V1 after vaccine administration. Specific immunoglobulin G (IgG) antibodies against SARS-CoV-2 S protein were detected in 96% and 98% of subjects at V1 and V2, respectively, although IgG titers decreased significantly between both time points., Conclusions: Our findings show that DS individuals develop an effective immune response to usual regimes of SARS-CoV-2 vaccination., Competing Interests: Potential conflicts of interest. E. P.-A. reports fees for Advisory Board participation from Pharmamar and AstraZeneca. D. R. d. A. reports grant number 19/00634 from Instituto Carlos III and grant number 2021A/2069 from Fondation Jerome Lejeune; payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing, or educational events from Universidad Complutense de Madrid (Título propio de experto en bioética clínica), Weill Cornell Medicine-Qatar (Division of Medical Ethics—several courses), Instituto Universitario de Investigación Ortega Y Gasset (Máster oficial en bioética clínica), Escuela Andaluza de Salud Pública (Curso Consultoría Ética Clínica [2022] y Máster en bioética [2021]), and Consejería de Salud, Comunidad De Madrid (Curso Consultoría Ética Clínica [November 2021]). All other authors report no potential conflicts. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed., (© The Author(s) 2022. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)

Objectives: To describe the clinical and epidemiological characteristics of adult patients with Down syndrome admitted to Spanish hospitals between 1997 and 2014. Secondary goals were to study trend changes over time, and to analyse differences between patients admitted to medical and surgical departments., Patients and Methods: Retrospective observational study on data collected from the Minimum Basic Dataset (MBDS, Conjunto Mínimo Básico de Datos [CMBD]) of admissions of adults with Down syndrome to hospitals belonging to the Spanish National Health System from 1 January 1997 through 31 December 2014. We analysed epidemiological and clinical variables., Results: We analysed 28,716 admissions of 16,874 adult patients with Down syndrome. Men accounted for 58.2% of the sample, and the mean age on admission was 41 ± 13 years, with an 11-year increase in mean age during the study period. Admissions among persons with Down syndrome increased by 5% during the study period, with a noticeable rise in admissions of older adults and to medical departments. Almost one-third of patients (31.8%) were admitted more than once. Age-adjusted mortality was 15.7%. The most common comorbid conditions were chronic obstructive pulmonary disease (25%), hypothyroidism (18.6%), and epilepsy (14.3%). The departments with the highest numbers of admissions were internal medicine (26.3%), pulmonary medicine (6.9%), and general surgery (5.25%)., Conclusion: Hospital admissions among Spanish adults with Down syndrome have increased in recent decades, especially in older patients. We identified substantial differences between patients admitted to medical and surgical departments., (© 2022 John Wiley & Sons Ltd.)

To describe congenital and acquired heart diseases in a Spanish cohort of adults with Down syndrome (DS), which could inform potential health recommendations for this population. Cross-sectional, observational study of adults with DS evaluated consecutively at a tertiary care, outpatient center between January 1 and December 31, 2019. The study population comprised 937 patients (51.8% men; median [IQR] age, 42 [18] years). An echocardiogram was available in the clinical chart of 420 patients (44.8%). The diagnosis of any form of heart disease was confirmed in 211 patients (22.5%): 101 (10.8%) had congenital heart defects, 80 (8.5%) simultaneous congenital and valvular heart diseases, and 30 (3.2%) isolated valvular heart disease. 111 patients (52.6% of those with congenital or valvular heart disease) had received corrective cardiac surgery. A total of 65 individuals were receiving medical management alone (30.8%), while 35 did not require any treatment because their cardiac disease was mild (16.6%). We found a high overall prevalence of heart disease in patients with DS, higher than previously reported for the pediatric population. Management of cardiovascular disease in adults with DS differs from that of the general population and should include universal echocardiography-based screening., (© 2022. The Author(s).)

Background: Down syndrome (DS) is considered the most frequent cause of early-onset Alzheimer's disease (AD), and the typical pathophysiological signs are present in almost all individuals with DS by the age of 40. Despite of this evidence, the investigation on the pre-dementia stages in DS is scarce. In the present study we analyzed the complexity of brain oscillatory patterns and neuropsychological performance for the characterization of mild cognitive impairment (MCI) in DS., Materials and Methods: Lempel-Ziv complexity (LZC) values from resting-state magnetoencephalography recordings and the neuropsychological performance in 28 patients with DS [control DS group (CN-DS) ( n = 14), MCI group (MCI-DS) ( n = 14)] and 14 individuals with typical neurodevelopment (CN-no-DS) were analyzed., Results: Lempel-Ziv complexity was lowest in the frontal region within the MCI-DS group, while the CN-DS group showed reduced values in parietal areas when compared with the CN-no-DS group. Also, the CN-no-DS group exhibited the expected pattern of significant increase of LZC as a function of age, while MCI-DS cases showed a decrease. The combination of reduced LZC values and a divergent trajectory of complexity evolution with age, allowed the discrimination of CN-DS vs. MCI-DS patients with a 92.9% of sensitivity and 85.7% of specificity. Finally, a pattern of mnestic and praxic impairment was significantly associated in MCI-DS cases with the significant reduction of LZC values in frontal and parietal regions ( p = 0.01)., Conclusion: Brain signal complexity measured with LZC is reduced in DS and its development with age is also disrupted. The combination of both features might assist in the detection of MCI within this population., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Fernández, Ramírez-Toraño, Bruña, Zuluaga, Esteba-Castillo, Abásolo, Moldenhauer, Shumbayawonda, Maestú and García-Alba.)

Background: Despite presenting higher risk of dementia, mild cognitive impairment (MCI) is not well defined in Down syndrome population., Objective: We aimed to describe cognitive and neuropsychological patterns associated with MCI in Down syndrome individuals., Method: Two groups of adults with Down syndrome (control and prodromal) were studied throughout 3 years. Two linear mixed models and a model including the variables that best predicted group membership were built., Results: Behavioural Regulation Index (BRI) (Behaviour Rating Inventory of Executive Function test) and the model composed of BRI, abstraction and delayed verbal memory were the variable and model best predicting group membership, respectively., Conclusion: Suggest a diagnosis of MCI when BRI is the earliest change perceived by caregivers and this is combined with low scores in abstract thinking, and when an amnesic pattern in delayed verbal memory is observed, but adaptive skills are preserved., (© 2021 John Wiley & Sons Ltd.)

Adults with Down syndrome (DS) have lower bone mineral density (BMD) than the general population. The objective of our study was to describe bone mineral status in DS population through volumetric BMD (vBMD) and trabecular bone score (TBS). Retrospective study of 297 subjects recruited from the Adult DS Outpatient Clinic of a tertiary care hospital in Spain, who underwent a bone densitometry for clinical purposes between January 2010 and June 2015. vBMD determination and TBS analysis on conventional DXA (Hologic QDR 4500) densitometer were performed in this cohort. The mean (±SD) age of our population was 34.3 (±10.9) years; 51% were women. Trabecular vBMD at total hip and femoral neck was lower in males than in females (191.7 ± 48.4 mg/cm 3 vs 206.9 ± 46.7 mg/cm 3 , p = 0.007, and 250.5 ± 70.1 mg/cm 3 vs 275.7 ± 66.2 mg/cm 3 , p = 0.002, respectively). Trabecular and cortical vBMD decreased with age, but age decline in trabecular vBMD was more pronounced in males. Likewise, lumbar TBS declined with age being normal in 63%, low in 29% and very low in 8% of subjects with DS, without differences between sexes. TBS showed a positive correlation (r = 0.37; p < 0.001, Kappa index= 0.275) with conventional DXA lumbar Z-score. vBMD at the hip showed lower values in DS subjects than in the general population, especially in males. Moreover, TBS was also lower at lumbar spine. Therefore, both assessments could be used as complementary tools to areal BMD (Z-score) to assess bone status in DS subjects., Competing Interests: Disclosures /Conflict of Interest The authors do not declare conflicts of interest regarding this article., (Copyright © 2021 The International Society for Clinical Densitometry. Published by Elsevier Inc. All rights reserved.)

Whether the increased risk for coronavirus disease 2019 (COVID-19) hospitalization and death observed in Down syndrome (DS) are disease specific or also occur in individuals with DS and non-COVID-19 pneumonias is unknown. This retrospective cohort study compared COVID-19 cases in persons with DS hospitalized in Spain reported to the Trisomy 21 Research Society COVID-19 survey ( n = 86) with admissions for non-COVID-19 pneumonias from a retrospective clinical database of the Spanish Ministry of Health ( n = 2832 patients). In-hospital mortality rates were significantly higher for COVID-19 patients (26.7% vs. 9.4%), especially among individuals over 40 and patients with obesity, dementia, and/or epilepsy. The mean length of stay of deceased patients with COVID-19 was significantly shorter than in those with non-COVID-19 pneumonias. The rate of admission to an ICU in patients with DS and COVID-19 (4.3%) was significantly lower than that reported for the general population with COVID-19. Our findings confirm that acute SARS-CoV-2 infection leads to higher mortality than non-COVID-19 pneumonias in individuals with DS, especially among adults over 40 and those with specific comorbidities. However, differences in access to respiratory support might also account for some of the heightened mortality of individuals with DS with COVID-19.

Introduction and Objectives: The clinical problems of adults with Down syndrome seem to differ from those of the general population. To better understand these differences, we list the demographic and clinical characteristics of adults with Down syndrome admitted to Spanish internal medicine departments during 2005-2014., Patients and Methods: We conducted an observational retrospective study using data collected from the minimum basic data set on hospitalisation episodes of adults with Down syndrome in the internal medicine departments of Spain's National Health System from 2005 to 2014. We analysed the patients' epidemiological, clinical and societal data., Results: A total of 7548 hospitalisation episodes from 3786 patients were recorded. Some 56.6% of the patients were male with a mean age (±SD) of 47±13 years, and 715 of the patients died (18.9%). The age-adjusted mortality was 26.6%, and the mean stay was 9.6±12 days. The hospitalisation was for respiratory disease in 3684 episodes (48.8%) and for cardiac origin in 760 (10%). The most common comorbidities were hypothyroidism (27.1%, 2043 episodes), epilepsy (24.1%, 1819 episodes) and dementia (15.4%, 1162 episodes)., Conclusions: The hospitalisation of adults with Down syndrome in internal medicine departments has increased in the past decade. Although the reasons for hospitalisation, mean stay and cost per episode for this population are similar to those of the general population treated by internal medicine departments, the age-adjusted hospital mortality was significantly greater., (Copyright © 2019 Elsevier España, S.L.U. and Sociedad Española de Medicina Interna (SEMI). All rights reserved.)

Patients with Down syndrome (DS) often have a high occurrence of obstructive sleep apnea-hypopnea (OSA) syndrome. We studied a large cohort of adults with DS attended due to clinical suspicion of OSA. A standardized questionnaire and full medical assessment were conducted, including a sleep study. One hundred and fifty-seven DS individuals were studied, with a mean ± SD age of 36 ± 10 years, 40.7% women, BMI 29.4 ± 5.6 kg/m 2 . The main clinical symptom was daytime sleepiness (64.9%). A sleep study was conducted in 114 patients. All 114 DS patients were diagnosed with OSA, with a predominance of obstructive and hypopnea events, (apnea-hypopnoea index, AHI, 35.0 ± 26.6), with an oxygen desaturation index of 32.9, and a Tc90% of 24.7%. Continuous positive airway pressure (CPAP) treatment was implemented in 75 (65.8%) of subjects. Tolerance was considered good in 75% of them, with a high compliance of 79.2% >4 hr/day (mean 7.1 hr/day), resulting in a symptomatic improvement in 58.7% of them. Obstructive sleep apnea is frequently confirmed in patients with DS when it clinically suspected. Treatment with CPAP in DS is feasible, and with higher adherence than in adults with normal cognitive functioning., (© 2020 Wiley Periodicals LLC.)

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., (© 2020 Wiley Periodicals LLC.)

Objectives: Although the reasons are unknown, the prevalence of arterial hypertension and atherosclerotic cardiovascular events in the adult population with Down syndrome (SD) is anecdotal. To better understand this finding, we evaluated the haemodynamic characteristics of a cohort of adults with SD., Methods: We conducted a cross-sectional study of adults with SD recruited consecutively from the outpatient clinics of an internal medicine department between June and November 2018. We collected demographic, clinical and laboratory variables and employed a thoracic bioimpedance device (HOTMAN® System) for the haemodynamic measures. Outpatient blood pressure monitoring (OBPM) was conducted on a subgroup of participants., Results: Twenty-six participants (mean age, 45±11years) participated in the study (50% men). The sample's mean blood pressure (BP) was 109/69±11/9mmHg, with a mean heart rate of 60±12bpm. None of the participants had hypertension. The predominant haemodynamic profile consisted of normal dynamism (65%), normal BP (96%), hypochronotropism (46%), normal inotropism (50%) and hypervolaemia (54%), with normal peripheral vascular resistance values (58%). Twelve participants underwent OBPM (46%). The mean 24-h systolic BP, diastolic BP, mean BP and mean heart rate were 105±11mmHg, 67±11mmHg, 80±11mmHg and 61±6bpm, respectively., Conclusions: The most common haemodynamic profile observed in adults with SD consisted of hypochronotropism and hypervolaemia, with normal values for peripheral vascular resistance and optimal mean BP values. There were no participants with hypertension in our sample., (Copyright © 2019 Elsevier España, S.L.U. and Sociedad Española de Medicina Interna (SEMI). All rights reserved.)

Down syndrome (DS) has been considered a unique model for the investigation of Alzheimer's disease (AD) but intermediate stages in the continuum are poorly defined. Considering this, we investigated the neurophysiological (i.e., magnetoencephalography [MEG]) and neuropsychological patterns of mild cognitive impairment (MCI) and AD in middle-aged adults with DS. The sample was composed of four groups: Control-DS (n = 14, mean age 44.64 ± 3.30 years), MCI-DS (n = 14, 51.64 ± 3.95 years), AD-DS (n = 13, 53.54 ± 6.58 years), and Control-no-DS (healthy controls, n = 14, 45.21 ± 4.39 years). DS individuals were studied with neuropsychological tests and MEG, whereas the Control-no-DS group completed only the MEG session. Our results showed that the AD-DS group exhibited a significantly poorer performance as compared with the Control-DS group in all tests. Furthermore, this effect was crucially evident in AD-DS individuals when compared with the MCI-DS group in verbal and working memory abilities. In the neurophysiological domain, the Control-DS group showed a widespread increase of theta activity when compared with the Control-no-DS group. With disease progression, this increased theta was substituted by an augmented delta, accompanied with a reduction of alpha activity. Such spectral pattern-specifically observed in occipital, posterior temporal, cuneus, and precuneus regions-correlated with the performance in cognitive tests. This is the first MEG study in the field incorporating both neuropsychological and neurophysiological information, and demonstrating that this combination of markers is sensitive enough to characterize different stages along the AD continuum in DS., (Copyright © 2019 Elsevier Inc. All rights reserved.)