Body composition parameters and sarcopenia in adults with Down syndrome: a case-control study.

BACKGROUND: Individuals with Down syndrome (DS) experience premature aging. Whether accelerated aging involves changes in body composition parameters and is associated with early development of sarcopenia is unclear. AIMS: To compare parameters of body composition and the prevalence of sarcopenia between adults with DS and the general population. METHODS: Body composition was assessed by whole-body dual-energy X-ray absorptiometry (DXA). Fat mass (FMI) and skeletal mass indices (SMI) were calculated as the ratio between total body fat mass and appendicular lean mass and the square of height, respectively. Fat mass distribution was assessed by the android/gynoid fat ratio (A/G). Sarcopenia was defined according to the criteria and cut-points recommended by the European Working Group on Sarcopenia in Older People 2 (EWGSOP2). Data on age- and sex-matched non-DS controls were retrieved from the 2001-2002 National Health and Nutrition Examination Survey (NHANES) population. RESULTS: Sixty-four DS adults (mean age 37.2 ± 12.0 years, 20.3% women) were enrolled and compared with age- and sex-matched NHANES participants (n = 256), in a 1:4 ratio. FMI (7.96 ± 3.18 kg/m2 vs. 8.92 ± 4.83 kg/m2, p = 0.135), SMI (7.38 ± 1.01 kg/m2 vs. 7.46 ± 2.77 kg/m2, p = 0.825) and A/G (0.98 ± 0.17 vs. 1.01 ± 0.22, p = 0.115) were not significantly different between DS and control participants. When the sample was stratified by sex, women with DS had a higher FMI compared with their NHANES controls (10.16 ± 4.35 kg/m2 vs. 8.11 ± 4.29 kg/m2, p < 0.001), while men with DS had lower A/G ratio (1.04 ± 0.16 vs. 1.11 ± 0.22, p = 0.002). Sarcopenia was more frequent in individuals with DS than in controls (35.6% vs. 19.9%, p = 0.007). This association was stronger in men 40 years and older. CONCLUSIONS: Adults with DS have a higher prevalence of sarcopenia compared with the general population. This finding suggests that DS is associated with early muscle aging and calls for the design of interventions targeting the skeletal muscle to prevent or treat sarcopenia.

Managing Non-Cancer Chronic Pain in Frail Older Adults: A Pilot Study Based on a Multidisciplinary Approach.

Considering the multidimensionality of chronic pain, it is crucial to develop comprehensive strategies for its effective management. However, establishing well-defined, evidence-based guidelines for such approaches remains challenging. To overcome this, we present the finding from a 4-month intervention to enhance the management of non-cancer chronic pain in older adults with pre-frailty and frailty. The intervention's core elements comprised a multidisciplinary individualized plan, a case manager, and patient education. This pilot study involved 22 participants (≥65 years). It assessed changes in pain frequency and intensity (pain scale), frailty (Fried frailty phenotype criteria), and medication adherence (Brief Adherence Rating Scale) before and after the 4-month intervention. The results were encouraging: pain frequency and intensity and frailty score tended to decrease, and medication adherence showed significant improvement. This preliminary small-scale pilot study provides a foundation for further research and for exploring the potential scalability of this multidisciplinary patient-centred intervention.

Neuropsychological measures of post-COVID-19 cognitive status.

Background: COVID-19 may result in persistent symptoms in the post-acute phase, including cognitive and neurological ones. The aim of this study is to investigate the cognitive and neurological features of patients with a confirmed diagnosis of COVID-19 evaluated in the post-acute phase through a direct neuropsychological evaluation. Methods: Individuals recovering from COVID-19 were assessed in an out-patient practice with a complete neurological evaluation and neuropsychological tests (Mini-Mental State Examination; Rey Auditory Verbal Test, Multiple Feature Target Cancellation Test, Trial Making Test, Digit Span Forward and Backward, and Frontal Assessment Battery). Pre- and post-COVID-19 global and mental health status was assessed along with the history of the acute phase of infection. Post-COVID-19 cognitive status was modeled by combining persistent self-reported COVID-related cognitive symptoms and pathologic neuropsychological tests. Results: A total of 406 individuals (average age 54.5 ± 15.1 years, 45.1% women) were assessed on average at 97.8 ± 48.0 days since symptom onset. Persistent self-reported neurological symptoms were found in the areas of sleep (32%), attention (31%), and memory (22%). The MMSE mean score was 28.6. In total, 84 subjects (20.7%) achieved pathologic neuropsychological test results. A high prevalence of failed tests was found in digit span backward (18.7%), trail making (26.6%), and frontal assessment battery (10.9%). Cognitive status was associated with a number of factors including cardiovascular disease history, persistent fatigue, female sex, age, anxiety, and mental health stress. Conclusion: COVID-19 is capable of eliciting persistent measurable neurocognitive alterations particularly relevant in the areas of attention and working memory. These neurocognitive disorders have been associated with some potentially treatable factors and others that may stratify risk at an early stage.

Frailty, multimorbidity patterns and mortality in institutionalized older adults in Italy.

BACKGROUND: Little is known on how frailty influences clinical outcomes in persons with specific multimorbidity patterns. AIMS: To investigate the interplay between multimorbidity and frailty in the association with mortality in older individuals living in nursing homes (NH). METHODS: We considered 4,131 NH residents aged 60 years and over, assessed through the interRAI LTCF instrument between 2014 and 2018. Follow-up was until 2019. Considering four multimorbidity patterns identified via principal component analysis, subjects were stratified in tertiles (T) with respect to their loading values. Frailty Index (FI) considered 23 variables and a cut-off of 0.24 distinguished between high and low frailty levels. For each pattern, all possible combinations of tertiles and FI were evaluated. Their association (Hazard Ratio [HR] and 95% confidence interval) with mortality was tested in Cox regression models. RESULTS: In the heart diseases and dementia and sensory impairments patterns, the hazard of death increases progressively with patterns expression and frailty severity (being HR T3 vs. T1 = 2.36 [2.01-2.78]; HR T3 vs. T1 = 2.12 [1.83-2.47], respectively). In heart, respiratory and psychiatric diseases and diabetes, musculoskeletal and vascular diseases patterns, frailty seems to have a stronger impact on mortality than patterns' expression. DISCUSSION: Frailty increases mortality risk in all the patterns and provides additional prognostic information in NH residents with different multimorbidity patterns. CONCLUSIONS: These findings support the need to routinely assess frailty. Older people affected by specific groups of chronic diseases need a specific care approach and have high risk of negative health outcomes.

Prevalence and management of dysphagia in nursing home residents in Europe and Israel: the SHELTER Project.

BACKGROUND: Dysphagia is a frequent condition in older nursing home residents (NHRs) which may cause malnutrition and death. Nevertheless, its prevalence is still underestimated and there is still debate about the appropriateness and efficacy of artificial nutrition (AN) in subjects with severe dysphagia. The aim is to assess the prevalence of dysphagia in European and Israeli NHRs, its association with mortality, and the relationship of different nutritional interventions, i.e. texture modified diets and AN-with weight loss and mortality. METHODS: A prospective observational study of 3451 European and Israeli NHRs older than 65 years, participating in the SHELTER study from 2009 to 2011, at baseline and after 12 months. All residents underwent a standardized comprehensive evaluation using the interRAI Long Term Care Facility (LTCF). Cognitive status was assessed using the Cognitive Performance Scale (CPS), functional status using Activities of Daily Living (ADL) Hierarchy scale. Trained staff assessed dysphagia at baseline by clinical observation. Data on weight loss were collected for all participants at baseline and after 12 months. Deaths were registered by NH staff. RESULTS: The prevalence of dysphagia was 30.3%. During the one-year follow-up, the mortality rate in subjects with dysphagia was significantly higher compared with that of non-dysphagic subjects (31.3% vs 17.0%,p = 0,001). The multivariate analysis showed that NHRs with dysphagia had 58.0% higher risk of death within 1 year compared with non-dysphagic subjects (OR 1.58, 95% CI, 1.31-1.91). The majority of NHRs with dysphagia were prescribed texture modified diets (90.6%), while AN was used in less than 10% of subjects. No statistically significant difference was found concerning weight loss and mortality after 12 months following the two different nutritional treatments. CONCLUSIONS: Dysphagia is prevalent among NHRs and it is associated with increased mortality, independent of the nutritional intervention used. Noticeably, after 12 months of nutritional intervention, NHRs treated with AN had similar mortality and weight loss compared to those who were treated with texture modified diets, despite the clinical conditions of patients on AN were more compromised.

Differences in clinical presentation, severity, and treatment of COVID-19 among individuals with Down syndrome from India and high-income countries: Data from the Trisomy 21 Research Society survey.

Background: People with Down syndrome (DS) are one of the highest risk groups for mortality associated with COVID-19, but outcomes may differ across countries due to different co-morbidity profiles, exposures, and societal practices, which could have implications for disease management. This study is designed to identify differences in clinical presentation, severity, and treatment of COVID-19 between India and several high-income countries (HICs). Methods: We used data from an international survey to examine the differences in disease manifestation and management for COVID-19 patients with DS from India vs HIC. De-identified survey data collected from April 2020 to August 2021 were analysed. Results: COVID-19 patients with DS from India were on average nine years younger than those from HICs. Comorbidities associated with a higher risk for severe COVID-19 were more frequent among the patients from India than from HICs. Hospitalizations were more frequent among patients from India as were COVID-19-related medical complications. Treatment strategies differed between India and HICs, with more frequent use of antibiotics in India. The average severity score of 3.31 was recorded for Indian DS in contrast to 2.3 for European and 2.04 for US cases. Conclusions: Presentation and outcomes of COVID-19 among individuals with DS were more severe for patients from India than for those from HIC. Global efforts should especially target vaccination campaigns and other risk-reducing interventions for individuals with DS from low-income countries.

Neuropsychological Measures of Long COVID-19 Fog in Older Subjects.

Coronavirus disease 2019 is known to impact older people more severely and to cause persistent symptoms during the recovery phase, including cognitive and neurologic ones. We investigated the cognitive and neurologic features of 100 elderly patients with confirmed diagnosis of coronavirus disease 2019 evaluated in the postacute phase through a direct neuropsychological evaluation consisting on Mini Mental State Examination and 8 neuropsychological tests. Overall, a total of 33 participants were found to perform at a level considered to be pathologic; more specifically, 33%, 23%, and 20% failed on Trial Making, Digit Span Backwards, and Frontal Evaluation Battery tests, respectively.

Comorbidity patterns in institutionalized older adults affected by dementia.

Introduction: Dementia is common in nursing homes (NH) residents. Defining dementia comorbidities is instrumental to identify groups of persons with dementia that differ in terms of health trajectories and resources consumption. We performed a cross-sectional study to identify comorbidity patterns and their associated clinical, behavioral, and functional phenotypes in institutionalized older adults with dementia. Methods: We analyzed data on 2563 Italian NH residents with dementia, collected between January 2014 and December 2018 using the multidimensional assessment instrument interRAI Long-Term Care Facility (LTCF). A standard principal component procedure was used to identify comorbidity patterns. Linear regression analyses were used to ascertain correlates of expression of the different patterns. Results: Among NH residents with dementia, we identified three different comorbidity patterns: (1) heart diseases, (2) cardiovascular and respiratory diseases and sensory impairments, and (3) psychiatric diseases. Older age significantly related to increased expression of the first two patterns, while younger patients displayed increased expression of the third one. Recent hospital admissions were associated with increased expression of the heart diseases pattern (ß = 0.028; 95% confidence interval [CI] 0.003 to 0.05). Depressive symptoms and delirium episodes increased the expression of the psychiatric diseases pattern (ß = 0.130, 95% CI 0.10 to 0.17, and ß 0.130, CI 0.10 to 0.17, respectively), while showed a lower expression of the heart diseases pattern. Discussion: We identified different comorbidity patterns within NH residents with dementia that differ in term of clinical and functional profiles. The prompt recognition of health needs associated to a comorbidity pattern may help improve long-term prognosis and quality of life of these individuals. Highlights: Defining dementia comorbidities patterns in institutionalized older adults is key.Institutionalized older adults with dementia express different care needs.Comorbidity patterns are instrumental to identify different patients' phenotypes.Phenotypes vary in terms of health trajectories and demand different care plans.Prompt recognition of phenotypes in nursing homes can positively impact on outcomes.

Biochemical Discrimination of the Down Syndrome-Related Metabolic and Oxidative/Nitrosative Stress Alterations from the Physiologic Age-Related Changes through the Targeted Metabolomic Analysis of Serum.

Down Syndrome (DS) is a neurodevelopmental disorder that is characterized by an accelerated aging process, frequently associated with the development of Alzheimer's disease (AD). Previous studies evidenced that DS patients have various metabolic anomalies, easily measurable in their serum samples, although values that were found in DS patients were compared with those of age-matched non-DS patients, thus hampering to discriminate the physiologic age-related changes of serum metabolites from those that are truly caused by the pathologic processes associated with DS. In the present study we performed a targeted metabolomic evaluation of serum samples from DS patients without dementia of two age classes (Younger DS Patients, YDSP, aging 20-40 years; Aged DS Patients, ADSP, aging 41-60 years), comparing the results with those that were obtained in two age classes of non-DS patients (Younger non-DS Patients, YnonDSP, aging 30-60 years; Aged-nonDS Patients, AnonDSP, aging 75-90 years). Of the 36 compounds assayed, 30 had significantly different concentrations in Pooled non-DS Patients (PnonDSP), compared to Pooled DS Patients (PDSP). Age categorization revealed that 11/30 compounds were significantly different in AnonDSP, compared to YnonDSP, indicating physiologic, age-related changes of their circulating concentrations. A comparison between YDSP and ADSP showed that 19/30 metabolites had significantly different values from those found in the corresponding classes of non-DS patients, strongly suggesting pathologic, DS-associated alterations of their serum levels. Twelve compounds selectively and specifically discriminated PnonDSP from PDSP, whilst only three discriminated YDSP from ADSP. The results allowed to determine, for the first time and to the best of our knowledge, the true, age-independent alterations of metabolism that are measurable in serum and attributable only to DS. These findings may be of high relevance for better strategies (pharmacological, nutritional) aiming to specifically target the dysmetabolism and decreased antioxidant defenses that are associated with DS.

COVID-19 Vaccination of Individuals with Down Syndrome-Data from the Trisomy 21 Research Society Survey on Safety, Efficacy, and Factors Associated with the Decision to Be Vaccinated.

Individuals with Down syndrome (DS) are among the groups with the highest risk for severe COVID-19. Better understanding of the efficacy and risks of COVID-19 vaccines for individuals with DS may help improve uptake of vaccination. The T21RS COVID-19 Initiative launched an international survey to obtain information on safety and efficacy of COVID-19 vaccines for individuals with DS. De-identified survey data collected between March and December 2021 were analyzed. Of 2172 individuals with DS, 1973 (91%) had received at least one vaccine dose (57% BNT162b2), 107 (5%) were unvaccinated by choice, and 92 (4%) were unvaccinated for other reasons. Most participants had either no side effects (54%) or mild ones such as pain at the injection site (29%), fatigue (12%), and fever (7%). Severe side effects occurred in <0.5% of participants. About 1% of the vaccinated individuals with DS contracted COVID-19 after vaccination, and all recovered. Individuals with DS who were unvaccinated by choice were more likely to be younger, previously recovered from COVID-19, and also unvaccinated against other recommended vaccines. COVID-19 vaccines have been shown to be safe for individuals with DS and effective in terms of resulting in minimal breakthrough infections and milder disease outcomes among fully vaccinated individuals with DS.

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

OBJECTIVE: People 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. METHODS: We 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. RESULTS: We 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. DISCUSSION: Subjects 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.

Oropharyngeal Dysphagia After Hospitalization for COVID-19 Disease: Our Screening Results.

A high percentage of patients suffered symptoms also after recovery from the Coronavirus Disease-2019 (COVID-19) infection. It is not well clear what are the specific long-term sequelae (complications and symptoms). During the acute phase the patients may develop a multi-organ system pathology including aerodigestive tract. As the pathophysiology of COVID-19 emerges, the aim of our study was to describe the prevalence of oropharyngeal dysphagia after COVID-19 disease. From March to July 2020 we enrolled patients recovered from SARS-CoV-2 infection who had been previously hospitalized for the disease. They were screened for dysphagia by mean of the Eating Assessment Tool-10 (EAT-10). The cases with EAT-10 score > 3 were graded for the aspiration risk by applying the Gugging Swallowing Screen (GUSS) and were submitted to the Swal-QoL questionnaire. The cases with a GUSS score > 19 were subjected to FEES. 8/117 (7%) patients had positive screening result. 4/8 (50%) revealed an abnormal health related quality of life in oropharyngeal dysphagia with a mean Swal-QoL score of 69.73. The most affected domain was the "time of meals" (mean score 65) following by the "sleep" (mean score 66) and "eating desire" (mean score 72). 1/8 cases showed increased risk for aspiration and did not showed endoscopic signs of oropharyngeal dysphagia. Our results showed that the prevalence of upper dysphagia after hospitalization for SARS-CoV-2 is not anecdotal and that probably this long-lasting sequela has a psychogenic etiology.

Prevalence and Predictors of Persistence of COVID-19 Symptoms in Older Adults: A Single-Center Study.

OBJECTIVES: Symptom persistence weeks after laboratory-confirmed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) clearance is a relatively common long-term complication of Coronavirus disease 2019 (COVID-19). Little is known about this phenomenon in older adults. The present study aimed at determining the prevalence of persistent symptoms among older COVID-19 survivors and identifying symptom patterns. DESIGN: Cross-sectional study. SETTING AND PARTICIPANTS: We analyzed data collected in people 65 years and older (n = 165) who were hospitalized for COVID-19 and then admitted to the Day Hospital Post-COVID 19 of the Fondazione Policlinico Universitario "Agostino Gemelli" IRCCS (Rome, Italy) between April and December 2020. All patients tested negative for SARS-CoV-2 and met the World Health Organization criteria for quarantine discontinuation. MEASURES: Patients were offered multidisciplinary individualized assessments. The persistence of symptoms was evaluated on admission using a standardized questionnaire. RESULTS: The mean age was 73.1 ± 6.2 years (median 72, interquartile range 27), and 63 (38.4%) were women. The average time elapsed from hospital discharge was 76.8 ± 20.3 days (range 25-109 days). On admission, 137 (83%) patients reported at least 1 persistent symptom. Of these, more than one-third reported 1 or 2 symptoms and 46.3% had 3 or more symptoms. The rate of symptom persistence was not significantly different when patients were stratified according to median age. Compared with those with no persistent symptoms, patients with symptom persistence reported a greater number of symptoms during acute COVID-19 (5.3 ± 3.0 vs 3.3 ± 2.0; P < .001). The most common persistent symptoms were fatigue (53.1%), dyspnea (51.5%), joint pain (22.2%), and cough (16.7%). The likelihood of symptom persistence was higher in those who had experienced fatigue during acute COVID-19. CONCLUSIONS AND IMPLICATIONS: Persistent symptoms are frequently experienced by older adults who have been hospitalized for COVID-19. Follow-up programs should be implemented to monitor and care for long-term COVID-19-related health issues.

COVID-19 and RA share an SPP1 myeloid pathway that drives PD-L1+ neutrophils and CD14+ monocytes.

We explored the potential link between chronic inflammatory arthritis and COVID-19 pathogenic and resolving macrophage pathways and their role in COVID-19 pathogenesis. We found that bronchoalveolar lavage fluid (BALF) macrophage clusters FCN1+ and FCN1+SPP1+ predominant in severe COVID-19 were transcriptionally related to synovial tissue macrophage (STM) clusters CD48hiS100A12+ and CD48+SPP1+ that drive rheumatoid arthritis (RA) synovitis. BALF macrophage cluster FABP4+ predominant in healthy lung was transcriptionally related to STM cluster TREM2+ that governs resolution of synovitis in RA remission. Plasma concentrations of SPP1 and S100A12 (key products of macrophage clusters shared with active RA) were high in severe COVID-19 and predicted the need for Intensive Care Unit transfer, and they remained high in the post-COVID-19 stage. High plasma levels of SPP1 were unique to severe COVID-19 when compared with other causes of severe pneumonia, and IHC localized SPP1+ macrophages in the alveoli of COVID-19 lung. Investigation into SPP1 mechanisms of action revealed that it drives proinflammatory activation of CD14+ monocytes and development of PD-L1+ neutrophils, both hallmarks of severe COVID-19. In summary, COVID-19 pneumonitis appears driven by similar pathogenic myeloid cell pathways as those in RA, and their mediators such as SPP1 might be an upstream activator of the aberrant innate response in severe COVID-19 and predictive of disease trajectory including post-COVID-19 pathology.

The Behavioral and Psychological Symptoms of Dementia in Down Syndrome Scale (BPSD-DS II): Optimization and Further Validation.

BACKGROUND: People with Down syndrome (DS) are at high risk to develop Alzheimer's disease dementia (AD). Behavioral and psychological symptoms of dementia (BPSD) are common and may also serve as early signals for dementia. However, comprehensive evaluation scales for BPSD, adapted to DS, are lacking. Therefore, we previously developed the BPSD-DS scale to identify behavioral changes between the last six months and pre-existing life-long characteristic behavior. OBJECTIVE: To optimize and further study the scale (discriminative ability and reliability) in a large representative DS study population. METHODS: Optimization was based on item irrelevance and clinical experiences obtained in the initial study. Using the shortened and refined BPSD-DS II, informant interviews were conducted to evaluate 524 individuals with DS grouped according to dementia status: no dementia (DS, N = 292), questionable dementia (DS + Q, N = 119), and clinically diagnosed dementia (DS + AD, N = 113). RESULTS: Comparing item change scores between groups revealed prominent changes in frequency and severity for anxious, sleep-related, irritable, restless/stereotypic, apathetic, depressive, and eating/drinking behavior. For most items, the proportion of individuals displaying an increased frequency was highest in DS + AD, intermediate in DS + Q, and lowest in DS. For various items within sections about anxious, sleep-related, irritable, apathetic, and depressive behaviors, the proportion of individuals showing an increased frequency was already substantial in DS + Q, suggesting that these changes may serve as early signals of AD in DS. Reliability data were promising. CONCLUSION: The optimized scale yields largely similar results as obtained with the initial version. Systematically evaluating BPSD in DS may increase understanding of changes among caregivers and (timely) adaptation of care/treatment.