Age of Alzheimer's disease diagnosis in people with Down syndrome and associated factors: Results from the Horizon 21 European Down syndrome consortium.

INTRODUCTION: People with Down syndrome (DS) have high risk of developing Alzheimer's disease (AD). This study examined mean ages of AD diagnosis and associations with co-occurring conditions among adults with DS from five European countries. METHODS: Data from 1335 people with DS from the Horizon 21 European DS Consortium were used for the analysis. RESULTS: Mean ages of AD diagnosis ranged between 51.4 (SD 7.0) years (United Kingdom) and 55.6 (SD 6.8) years (France). Sleep-related and mental health problems were associated with earlier age of AD diagnosis. The higher number of co-occurring conditions the more likely the person with DS is diagnosed with AD at an earlier age. DISCUSSION: Mean age of AD diagnosis in DS was relatively consistent across countries. However, co-occurring conditions varied and impacted on age of diagnosis, suggesting that improvements can be made in diagnosing and managing these conditions to delay onset of AD in DS. HIGHLIGHTS: Mean age of AD diagnosis was relatively consistent between countries Sleep problems and mental health problems were associated with earlier age of AD diagnosis APOE ε4 carriers were diagnosed with AD at an earlier age compared to non-carriers Number of co-occurring conditions was associated with earlier age of AD diagnosis No differences between level of intellectual disability and mean age of AD diagnosis.

Toward the right treatment at the right time: Modeling the trajectory of cognitive decline to identify the earliest age of change in people with Alzheimer's disease.

Introduction: Age is the greatest risk factor for Alzheimer's disease (AD). A limitation of randomized control trials in AD is a lack of specificity in the age ranges of participants who are enrolled in studies of disease-modifying therapies. We aimed to apply Emax (i.e., maximum effect) modeling as a novel approach to identity ideal treatment windows. Methods: Emax curves were fitted to longitudinal cognitive data of 101 participants with AD and 1392 healthy controls. We included the Mini-Mental State Examination (MMSE) and tests of verbal fluency and executive functioning. Results: In people with AD, the earliest decline in the MMSE could be detected in the 67-71 age band while verbal fluency declined from the 41-45 age band. In healthy controls, changes in cognition showed a later trajectory of decline. Discussion: Emax modeling could be used to design more efficient trials which has implications for randomized control trials targeting the earlier stages of AD.

The relationship between social cognitive processes and behavior changes in people with amnestic mild cognitive impairment or dementia using the Edinburgh Social Cognition Test (ESCoT).

OBJECTIVE: People with amnestic mild cognitive impairment (aMCI) or dementia often exhibit a decline in their social abilities, but few tests of social cognition exist that are suitable for clinical use. Moreover, the relationship between changes in behavior and impairments in social cognition is poorly understood. We examined the utility of the Edinburgh Social Cognition Test (ESCoT) in people with aMCI/dementia and explored associations between social cognition performance and behavior changes. METHOD: We administered the ESCoT and two established social cognition tests (the Reading the Mind in the Eyes and the Social Norms Questionnaire) to 28 people with aMCI or dementia and 28 age and sex matched cognitively healthy controls. Behavior change was measured using a semistructured interview which assesses behavioral abnormalities found in frontotemporal dementia. RESULTS: People with aMCI/dementia were impaired on the ESCoT affective theory of mind, ESCoT total score and the Reading the Mind in the Eyes. Behavior changes in the domains of apathy, loss of sympathy/empathy, perseveration, and psychotic symptoms were associated with poorer affective theory of mind scores. Disinhibition, loss of sympathy/empathy and hyperorality or altered food preferences were associated with cognitive theory of mind. All behaviors were significantly associated with poorer performance on ESCoT total score, but were not associated with performance on the Reading the Mind in the Eyes or the Social Norms Questionnaire. CONCLUSIONS: The ESCoT was sensitive to social cognition impairments in people with aMCI/dementia and it relates to behavior change in aMCI/dementia unlike established tests. Different subtests of the ESCoT were related to different behavior changes. These findings suggest that the ESCoT may be a clinically valuable tool when examining social cognition. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Common mental health disorders and cognitive decline in a longitudinal Down syndrome cohort.

BACKGROUND: Down syndrome is the most common genetic cause of intellectual disability and Alzheimer's disease. In the general population, common mental disorders (CMDs), including anxiety, depression and obsessive-compulsive disorder, are linked to cognitive decline and higher risk for dementia. It is not known how CMDs affect longer-term cognitive outcomes in Down syndrome, and there is often diagnostic uncertainty in older people with Down syndrome and psychiatric comorbidity. AIMS: To study the influence of CMDs on cognitive ability and whether they are related longitudinally to development of clinical signs of Alzheimer's disease in Down syndrome. METHOD: We followed 115 individuals with Down syndrome, 27 of whom were diagnosed with a CMD, over approximately 3 years. Changes in cognitive and behavioural outcomes between baseline and follow-up assessment were analysed, with comparisons made between those with and without a comorbid CMD. Age, gender, apolipoprotein E status and level of intellectual disability were included as covariates. RESULTS: No significant association between presence of a CMD and poorer performance on cognitive tasks or informant-rated decline over time was observed (P > 0.05). CONCLUSIONS: Our results suggest that a diagnosis of a CMD does not have a significant negative effect on long-term cognitive or behavioural outcomes in individuals with Down syndrome. In individuals with stable or treated CMD, subsequent cognitive decline is likely indicative of Alzheimer's disease rather than a consequence of mental disorder.

Identifying individuals with intellectual disability who access mental health support and are at high risk for adverse clinical outcomes: cohort study.

BACKGROUND: People with intellectual disability often experience aggressive challenging behaviour and mental health issues. It can be difficult to identify those who are at higher risk of adverse clinical outcomes when in clinical care. AIMS: To characterise potential subgroups in adults with intellectual disability referred to mental health services in those presenting with aggressive behaviour or common mental disorders (CMDs). METHOD: There were 836 adults (≥18 years) with intellectual disability and a record of aggressive challenging behaviour, and 205 patients with intellectual disability and CMDs, who were seen in specialist mental health services over a 5-year period. Cluster analysis was used to define patient characteristics associated with clinical outcome. RESULTS: Distinct patient groups with differentiated profiles were observed in people with intellectual disability displaying aggressive challenging behaviour, and in those presenting with CMDs. Characteristics of the aggressive behaviour group who experienced adverse outcomes included being <30 years old, being male, more mentions of aggression and agitation in their clinical record, a diagnosis of pervasive developmental disorder and prescription of psychotropic medication. Characteristics of the CMD cluster that experienced adverse clinical outcomes were being older, being a White male, having a mild intellectual disability and physical health concerns. CONCLUSIONS: People with intellectual disability who experience adverse clinical outcomes can be identified with a cluster analysis approach of common features, but differ by clinical presentation. This could be used not only to stratify this clinically heterogeneous population in terms of response to interventions, but also improve precision in the development of tailored interventions.

Exploring semantic verbal fluency patterns and their relationship to age and Alzheimer's disease in adults with Down syndrome.

INTRODUCTION: Adults with Down syndrome (DS) are at ultra-high risk of developing Alzheimer's disease (AD), characterized by poor episodic memory and semantic fluency in the preclinical phase in the general population. We explored semantic fluency performance in DS and its relationship to age, AD, and blood biomarkers. METHODS: A total of 302 adults with DS at baseline and 87 at follow-up from the London Down Syndrome Consortium cohort completed neuropsychological assessments. Blood biomarkers were measured with the single molecule array technique in a subset of 94 participants. RESULTS: Poorer verbal fluency performance was observed as age increases. Number of correct words declined in those with AD compared to those without over 2 years and was negatively correlated with neurofilament light (r = -0.37, P = .001) and glial fibrillary acidic protein (r = -0.31, P = .012). DISCUSSION: Semantic fluency may be useful as an early indicator of cognitive decline and provide additional information on AD-related change, showing associations with biomarkers in DS.

Multiple morbidity across the lifespan in people with Down syndrome or intellectual disabilities: a population-based cohort study using electronic health records.

BACKGROUND: The Down syndrome phenotype is well established, but our understanding of its morbidity patterns is limited. We comprehensively estimated the risk of multiple morbidity across the lifespan in people with Down syndrome compared with the general population and controls with other forms of intellectual disability. METHODS: In this matched population-based cohort-study design, we used electronic health-record data from the UK Clinical Practice Research Datalink (CRPD) from Jan 1, 1990, to June 29, 2020. We aimed to explore the pattern of morbidities throughout the lifespan of people with Down syndrome compared with people with other intellectual disabilities and the general population, to identify syndrome-specific health conditions and their age-related incidence. We estimated incidence rates per 1000 person-years and incidence rate ratios (IRRs) for 32 common morbidities. Hierarchical clustering was used to identify groups of associated conditions using prevalence data. FINDINGS: Between Jan 1, 1990, and June 29, 2020, a total of 10 204 people with Down syndrome, 39 814 controls, and 69 150 people with intellectual disabilities were included. Compared with controls, people with Down syndrome had increased risk of dementia (IRR 94·7, 95% CI 69·9-128·4), hypothyroidism (IRR 10·6, 9·6-11·8), epilepsy (IRR 9·7, 8·5-10·9), and haematological malignancy (IRR 4·7, 3·4-6·3), whereas asthma (IRR 0·88, 0·79-0·98), cancer (solid tumour IRR 0·75, 0·62-0·89), ischaemic heart disease (IRR 0·65, 0·51-0·85), and particularly hypertension (IRR 0·26, 0·22-0·32) were less frequent in people with Down syndrome than in controls. Compared to people with intellectual disabilities, risk of dementia (IRR 16·60, 14·23-19·37), hypothyroidism (IRR 7·22, 6·62-7·88), obstructive sleep apnoea (IRR 4·45, 3·72-5·31), and haematological malignancy (IRR 3·44, 2·58-4·59) were higher in people with Down syndrome, with reduced rates for a third of conditions, including new onset of dental inflammation (IRR 0·88, 0·78-0·99), asthma (IRR 0·82, 0·73-0·91), cancer (solid tumour IRR 0·78, 0·65-0·93), sleep disorder (IRR 0·74, 0·68-0·80), hypercholesterolaemia (IRR 0·69, 0·60-0·80), diabetes (IRR 0·59, 0·52-0·66), mood disorder (IRR 0·55, 0·50-0·60), glaucoma (IRR 0·47, 0·29-0·78), and anxiety disorder (IRR 0·43, 0·38-0·48). Morbidities in Down syndrome could be categorised on age-related incidence trajectories, and their prevalence clustered into typical syndromic conditions, cardiovascular diseases, autoimmune disorders, and mental health conditions. INTERPRETATION: Multiple morbidity in Down syndrome shows distinct patterns of age-related incidence trajectories and clustering that differ from those found in the general population and in people with other intellectual disabilities, with implications for provision and timing of health-care screening, prevention, and treatment for people with Down syndrome. FUNDING: The European Union's Horizon 2020 Research and Innovation Programme, the Jérôme Lejeune Foundation, the Alzheimer's Society, the Medical Research Council, the Academy of Medical Sciences, the Wellcome Trust, and William Harvey Research Limited.

Aggressive challenging behavior in adults with intellectual disability: An electronic register-based cohort study of clinical outcome and service use.

BACKGROUND: Aggressive challenging behavior in people with intellectual disability is a frequent reason for referral to secondary care services and is associated with direct harm, social exclusion, and criminal sanctions. Understanding the factors underlying aggressive challenging behavior and predictors of adverse clinical outcome is important in providing services and developing effective interventions. METHODS: This was a retrospective total-population cohort study using electronic records linked with Hospital Episode Statistics data. Participants were adults with intellectual disability accessing secondary services at a large mental healthcare provider in London, United Kingdom, between 2014 and 2018. An adverse outcome was defined as at least one of the following: admission to a mental health hospital, Mental Health Act assessment, contact with a psychiatric crisis team or attendance at an emergency department. RESULTS: There were 1,515 patient episodes related to 1,225 individuals, of which 1,019 episodes were reported as displaying aggressive challenging behavior. Increased episode length, being younger, psychotropic medication use, pervasive developmental disorder (PDD), more mentions of mood instability, agitation, and irritability, more contact with mental health professionals, and more mentions of social and/or home care package in-episode were all associated with increased odds of medium-high levels of aggression. Risk factors for an adverse clinical outcome in those who exhibited aggression included increased episode length, personality disorder, common mental disorder (CMD), more mentions of agitation in-episode, and contact with mental health professionals. PDD predicted better outcome. CONCLUSIONS: Routinely collected data confirm aggressive challenging behavior as a common concern in adults with intellectual disability who are referred for specialist support and highlight factors likely to signal an adverse outcome. Treatment targets may include optimizing management of CMDs and agitation.

Italian adaptation of the Edinburgh Social Cognition Test (ESCoT): A new tool for the assessment of theory of mind and social norm understanding.

The relevance of social cognition assessment has been formally described in the Diagnostic and Statistical Manual of Mental Disorders-5. However, social cognition tools evaluating different socio-cognitive components for Italian-speaking populations are lacking. The Edinburgh Social Cognition Test (ESCoT) is a new social cognition measure that uses animations of everyday social interactions to assess (i) cognitive theory of mind, (ii) affective theory of mind, (iii) interpersonal social norm understanding, and (iv) intrapersonal social norm understanding. Previous studies have shown that the ESCoT is a sensitive measure of social cognition in healthy and clinical populations in the United Kingdom. This work aimed to adapt and validate the ESCoT in an Italian population of healthy adults. A translation-back-translation procedure was followed to create and refine the Italian version. Then, 94 healthy adults (47 females, mean age 35 ± 15.9) completed the ESCoT, a battery of conventional social cognition tests (Yoni; Reading the Mind in the Eyes Strange Stories, and Social Norm Questionnaire, SNQ) and measures of intelligence and executive functions. Reliability, convergent validity, and predictors of performance on the ESCoT were examined. Results demonstrated good reliability of the ESCoT and an association between the ESCoT scores and some traditional social cognition tests (Yoni cognitive subscale, SNQ). Hierarchical regression results showed that the ESCoT total score was associated with age. Also, the ESCoT subscore (intrapersonal social norm understanding) was associated with education. These findings support the ESCoT as a valid tool testing social norm understanding, a reliable measure of social cognition for an adult Italian population, and provides further evidence that the ESCoT is sensitive to age- and education-related changes in social cognition, and it is a task not affected by general cognitive functioning.

An Investigation of the Validity of the Edinburgh Social Cognition Test (ESCoT) in Acquired Brain Injury (ABI).

OBJECTIVES: Social cognition is frequently impaired following an acquired brain injury (ABI) but often overlooked in clinical assessments. There are few validated and appropriate measures of social cognitive abilities for ABI patients. The current study examined the validity of the Edinburgh Social Cognition Test (ESCoT, Baksh et al., ) in measuring social cognition following an ABI. METHODS: Forty-one patients with ABI were recruited from a rehabilitation service and completed measures of general ability, executive functions and social cognition (Faux Pas; FP, Reading the Mind in the Eyes; RME, Social Norms Questionnaire; SNQ and the ESCoT). Forty-one controls matched on age, sex and years of education also performed the RME, SNQ and ESCoT. RESULTS: A diagnosis of ABI was significantly associated with poorer performance on all ESCoT measures and RME while adjusting for age, sex and years of education. In ABI patients, the ESCoT showed good internal consistency with its subcomponents and performance correlated with the other measures of social cognition demonstrating convergent validity. Better Trail Making Test performance predicted better ESCoT total, RME and SNQ scores. Higher TOPF IQ was associated with higher RME scores, while higher WAIS-IV working memory predicted better FP performance. CONCLUSIONS: The ESCoT is a brief, valid and internally consistent assessment tool able to detect social cognition deficits in neurological patients. Given the prevalence of social cognition deficits in ABI and the marked impact these can have on an individual's recovery, this assessment can be a helpful addition to a comprehensive neuropsychological assessment.

Diabetes and Obesity in Down Syndrome Across the Lifespan: A Retrospective Cohort Study Using U.K. Electronic Health Records.

OBJECTIVE: Down syndrome (DS) is the most common form of chromosomal trisomy. Genetic factors in DS may increase the risk for diabetes. This study aimed to determine whether DS is associated with an increased incidence of diabetes and the relationship with obesity across the life span compared with control patients. RESEARCH DESIGN AND METHODS: This matched population-based cohort study analyzed UK Clinical Practice Research Datalink data from 1990 to 2020. RESULTS: A total of 9,917 patients with DS and 38,266 control patients were analyzed. Diabetes rates were higher in patients with DS (incidence rate ratio 3.67; 95% CI 2.43-5.55; P < 0.0001) and peaked at a younger age (median age at diagnosis 38 [interquartile range 28-49] years vs. 53 [43-61] years in control patients). Incidence rates (per 1,000 person-years) for type 1 diabetes mellitus were 0.44 (95% CI 0.31-0.61) in patients with DS vs. 0.13 (0.09-0.17) in control patients. Type 2 diabetes mellitus (T2DM) rates were higher in patients with DS versus control patients in age-groups from 5 years up to 34 years. In patients with DS, peak mean BMI was higher and at a younger age (males 31.2 kg/m2 at age 31 years; females 32.1 kg/m2 at 43 years) versus control patients (males 29.5 kg/m2 at 54 years; females 29.2 kg/m2 at 51 years). Obesity was associated with an increased incidence of T2DM. CONCLUSIONS: At younger ages, the incidence of diabetes in patients with DS is up to four times that of control patients. Peak mean BMI is higher and established earlier in DS, contributing to T2DM risk. Further investigation into the relationship between obesity and diabetes in DS is required to inform treatment and prevention measures.

Susceptibility to COVID-19 Diagnosis in People with Down Syndrome Compared to the General Population: Matched-Cohort Study Using Primary Care Electronic Records in the UK.

BACKGROUND: During the COVID-19 pandemic, people with Down syndrome (DS) have experienced a more severe disease course and higher mortality rates than the general population. It is not yet known whether people with DS are more susceptible to being diagnosed with COVID-19. OBJECTIVE: To explore whether DS is associated with increased susceptibility to COVID-19. DESIGN: Matched-cohort study design using anonymised primary care electronic health records from the May 2021 release of Clinical Practice Research Datalink (CPRD) Aurum. SETTING: Electronic health records from approximately 1400 general practices (GPs) in England. PARTICIPANTS: 8854 people with DS and 34,724 controls matched for age, gender and GP who were registered on or after the 29th January 2020. MEASUREMENTS: The primary outcome was COVID-19 diagnosis between January 2020 and May 2021. Conditional logistic regression models were fitted to estimate associations between DS and COVID-19 diagnosis, adjusting for comorbidities. RESULTS: Compared to controls, people with DS were more likely to be diagnosed with COVID-19 (7.4% vs 5.6%, p ≤ 0.001, odds ratio (OR) = 1.35; 95% CI = 1.23-1.48). There was a significant interaction between people with DS and a chronic respiratory disease diagnosis excluding asthma and increased odds of a COVID-19 diagnosis (OR = 1.71; 95% CI = 1.20-2.43), whilst adjusting for a number of comorbidities. CONCLUSION: Individuals with DS are at increased risk for contracting COVID-19. Those with underlying lung conditions are particularly vulnerable during viral pandemics and should be prioritised for vaccinations.

Understanding inequalities in COVID-19 outcomes following hospital admission for people with intellectual disability compared to the general population: a matched cohort study in the UK.

OBJECTIVES: This study explores the hospital journey of patients with intellectual disabilities (IDs) compared with the general population after admission for COVID-19 during the first wave of the pandemic (when demand on inpatient resources was high) to identify disparities in treatment and outcomes. DESIGN: Matched cohort study; an ID cohort of 506 patients were matched based on age, sex and ethnicity with a control group using a 1:3 ratio to compare outcomes from the International Severe Acute Respiratory and emerging Infections Consortium WHO Clinical Characterisation Protocol UK. SETTING: Admissions for COVID-19 from UK hospitals; data on symptoms, severity, access to interventions, complications, mortality and length of stay were extracted. INTERVENTIONS: Non-invasive respiratory support, intubation, tracheostomy, ventilation and admission to intensive care units (ICU). RESULTS: Subjective presenting symptoms such as loss of taste/smell were less frequently reported in ID patients, whereas indicators of more severe disease such as altered consciousness and seizures were more common. Controls had higher rates of cardiovascular risk factors, asthma, rheumatological disorder and smoking. ID patients were admitted with higher respiratory rates (median=22, range=10-48) and were more likely to require oxygen therapy (35.1% vs 28.9%). Despite this, ID patients were 37% (95% CI 13% to 57%) less likely to receive non-invasive respiratory support, 40% (95% CI 7% to 63%) less likely to receive intubation and 50% (95% CI 30% to 66%) less likely to be admitted to the ICU while in hospital. They had a 56% (95% CI 17% to 102%) increased risk of dying from COVID-19 after they were hospitalised and were dying 1.44 times faster (95% CI 1.13 to 1.84) compared with controls. CONCLUSIONS: There have been significant disparities in healthcare between people with ID and the general population during the COVID-19 pandemic, which may have contributed to excess mortality in this group.

Markers of early changes in cognition across cohorts of adults with Down syndrome at risk of Alzheimer's disease.

INTRODUCTION: Down syndrome (DS), a genetic variant of early onset Alzheimer's disease (AD), lacks a suitable outcome measure for prevention trials targeting pre-dementia stages. METHODS: We used cognitive test data collected in several longitudinal aging studies internationally from 312 participants with DS without dementia to identify composites that were sensitive to change over time. We then conducted additional analyses to provide support for the utility of the composites. The composites were presented to an expert panel to determine the most optimal cognitive battery based on predetermined criteria. RESULTS: There were common cognitive domains across site composites, which were sensitive to early decline. The final composite consisted of memory, language/executive functioning, selective attention, orientation, and praxis tests. DISCUSSION: We have identified a composite that is sensitive to early decline and thus may have utility as an outcome measure in trials to prevent or delay symptoms of AD in DS.

The Association between Physical Activity and CAMDEX-DS Changes Prior to the Onset of Alzheimer's Disease in Down Syndrome.

BACKGROUND: People with Down syndrome are at ultra-high risk of developing Alzheimer's dementia. At present, there are no preventative or curative treatments. Evidence from sporadic Alzheimer's disease literature suggests that lifestyle factors including physical activity may help maintain cognitive and functional skills and reduce dementia risk. Our study aimed to explore the association between regular exercise undertaken by participants with Down syndrome and changes in dementia-related domains of cognition and function. This was to consider whether physical activity may be a protective measure to delay cognitive decline and dementia in Down syndrome. METHODS: Demographic, lifestyle, and health information was collected at baseline and at a two year follow up from 214 adults with Down syndrome without dementia, who also underwent assessment using the Cambridge Examination for Mental Disorders of Older People with Down Syndrome and Others with Intellectual Disabilities (CAMDEX-DS) and genetic analysis. Logistic regression models were used to examine the potential associations between decline in CAMDEX-DS domains and exercise whilst controlling for key variables. RESULTS: At baseline, engaging in moderate intensity exercise was associated with a 47% reduced risk of everyday skills decline and engaging in high intensity exercise was associated with a 62% reduced risk of decline in personality and behaviour. At follow-up, high levels of exercise were associated with an 87% reduced risk of decline in personality and behaviour. Moderate intensity exercise at baseline was associated with a 62% reduction in risk of decline during the follow-up period in memory and orientation. DISCUSSION: Based on our data it appears that regular moderate and high intensity exercise could reduce the risk of clinically detectable decline in a Down syndrome population with possible long-term benefits. People with Down syndrome may engage in less physical activity than their peers, and barriers remain which can prevent people with Down syndrome engaging in exercise. Our work highlights how important it is that people with Down syndrome are supported to be physically active, and to promote exercise as part of a healthy ageing plan. Clinical trials in this area would be justified to determine if engaging in exercise can lead to realistic improvements in maintaining functioning and delaying dementia onset in Down syndrome and to help develop guidance in this area.

Medical vulnerability of individuals with Down syndrome to severe COVID-19-data from the Trisomy 21 Research Society and the UK ISARIC4C survey.

BACKGROUND: Health conditions, immune dysfunction, and premature aging associated with trisomy 21 (Down syndrome, DS) may impact the clinical course of COVID-19. METHODS: The T21RS COVID-19 Initiative launched an international survey for clinicians or caregivers on patients with COVID-19 and DS. Data collected between April and October 2020 (N=1046) were analysed and compared with the UK ISARIC4C survey of hospitalized COVID-19 patients with and without DS. FINDINGS: The mean age of COVID-19 patients with DS in the T21RS survey was 29 years (SD = 18). Similar to the general population, the most frequent signs and symptoms of COVID-19 were fever, cough, and shortness of breath. Joint/muscle pain and vomiting or nausea were less frequent (p < 0.01), whereas altered consciousness/confusion were more frequent (p < 0.01). Risk factors for hospitalization and mortality were similar to the general population with the addition of congenital heart defects as a risk factor for hospitalization. Mortality rates showed a rapid increase from age 40 and were higher in patients with DS (T21RS DS versus non-DS patients: risk ratio (RR) = 3.5 (95%-CI=2.6;4.4), ISARIC4C DS versus non-DS patients: RR = 2.9 (95%-CI=2.1;3.8)) even after adjusting for known risk factors for COVID-19 mortality. INTERPRETATION: Leading signs/symptoms of COVID-19 and risk factors for severe disease course are similar to the general population. However, individuals with DS present significantly higher rates of medical complications and mortality, especially from age 40. FUNDING: Down Syndrome Affiliates in Action, DSMIG-USA, GiGi's Playhouse, Jerome Lejeune Foundation, LuMind IDSC Foundation, The Matthew Foundation, NDSS, National Task Group on Intellectual Disabilities and Dementia Practices.

The association between anxiety disorders and hippocampal volume in older adults.

The hippocampus, through its mediation of fear responses is thought to play a central role in the onset and maintenance of anxiety disorders. Prevalence of anxiety disorders remains high in older populations; however, little is known about their association with hippocampal changes in this age group. Due to differing levels of cortisol as adults age, age-related decreases in hippocampal volume, and the suggestion that age-related loss of neurogenesis results in anxiety disorders, this area requires investigation. We examined the association between hippocampal volume and anxiety disorders (social anxiety disorder, generalized anxiety disorder, agoraphobia, panic disorder, obsessive compulsive disorder and posttraumatic stress disorder) in 534 older adults participating in the Enquête de Santé Psychologique-Risques, Incidence et Traitement (ESPRIT) study of late-life neuropsychiatric disorders. Anxiety disorders were diagnosed using the Mini International Neuropsychiatric Interview MINI, French version 5.00. Cross-sectional analyses adjusted for age, educational level, gender, Mini-Mental State Examination scores, National Adult Reading Test scores, whole brain volume and depression found that a diagnosis of generalized anxiety disorder was positively associated with larger hippocampal volume. No other anxiety disorder was significantly associated with hippocampal volume. The present study is the first to examine the association between several anxiety disorders and hippocampal volume in an older population and the results highlight the need for further research relating to the relationship between hippocampal volume and anxiety disorders in older adults. (PsycInfo Database Record (c) 2021 APA, all rights reserved).

Social cognition in adults with autism spectrum disorders: Validation of the Edinburgh Social Cognition Test (ESCoT).

OBJECTIVE: Many existing tests of social cognition are not appropriate for clinical use, due to their length, complexity or uncertainty in what they are assessing. The Edinburgh Social Cognition Test (ESCoT) is a new test of social cognition that assesses affective and cognitive Theory of Mind as well as inter- and intrapersonal understanding of social norms using animated interactions. METHOD: To support the development of the ESCoT as a clinical tool, we derived cut-off scores from a neurotypical population (n = 236) and sought to validate the ESCoT in a sample of Autism Spectrum Disorder (ASD; n = 19) adults and neurotypical controls (NC; n = 38) matched on age and education. The ESCoT was administered alongside established tests and questionnaire measures of ASD, empathy, systemizing traits and intelligence. RESULTS: Performance on the subtests of the ESCoT and ESCoT total scores correlated with performance on traditional tests, demonstrating convergent validity. ASD adults performed poorer on all measures of social cognition. Unlike the ESCoT, performance on the established tests was predicted by verbal comprehension abilities. Using a ROC curve analysis, we showed that the ESCoT was more effective than existing tests at differentiating ASD adults from NC. Furthermore, a total of 42.11% of ASD adults were impaired on the ESCoT compared to 0% of NC adults. CONCLUSIONS: Overall these results demonstrate that the ESCoT is a useful test for clinical assessment and can aid in the detection of potential difficulties in ToM and social norm understanding.

Optimal age and outcome measures for Alzheimer's disease prevention trials in people with Down syndrome.

INTRODUCTION: People with Down syndrome (DS) typically develop Alzheimer's disease (AD) neuropathology before age 40, but a lack of outcome measures and longitudinal data have impeded their inclusion in randomized controlled trials (RCTs). METHODS: Cohort study. Event-based and dose-response Emax models were fitted to longitudinal cognitive data, to stage AD and determine the earliest ages of decline. Results informed sample size estimations for hypothetical RCTs of disease-modifying treatments that reduced decline by 35% or 75%. RESULTS: Seventy-five percent of participants progressed or remained stable in the AD staging model; effect sizes varied by age group and tests. Varied treatment effects could be detected with 50-200 people per arm when using sensitive cognitive outcome measures and targeting recruitment to ages 36 to 45 years. DISCUSSION: Efficient RCTs of AD preventative treatments can be conducted in the DS population using sensitive outcome measures to monitor early decline. Dose-response models could help tailor future RCTs.