Dementia in Rare Genetic Neurodevelopmental Disorders: A Systematic Literature Review.

BACKGROUND AND OBJECTIVES: Knowledge of young-onset Alzheimer disease in adults with Down syndrome has greatly improved clinical care. However, little is known about dementia in rare genetic neurodevelopmental disorders (RGNDs). In this review, a comprehensive overview is provided of reports on dementia and cognitive/adaptive trajectories in adults with RGNDs. METHODS: A systematic literature review was conducted in Embase, Medline ALL, and PsycINFO on December 6, 2022. The protocol was registered in PROSPERO (CRD42021223041). Search terms for dementia, cognitive and adaptive functioning, and RGNDs were combined using generic terms and the Orphanet database. Study characteristics and descriptive data on genetic diagnosis, clinical and neuropathologic features, comorbidities, and diagnostic methods were extracted using a modified version of the Cochrane Data Extraction Template. RESULTS: The literature search yielded 40 publications (17 cohorts, 23 case studies) describing dementia and/or cognitive or adaptive trajectories in adults with 14 different RGNDs. Dementia was reported in 49 individuals (5 cohorts, 20 cases) with a mean age at onset of 44.4 years. Diagnostics were not disclosed for half of the reported individuals (n = 25/49, 51.0%). A total of 44 different psychodiagnostic instruments were used. MRI was the most reported additional investigation (n = 12/49, 24.5%). Comorbid disorders most frequently associated with cognitive/adaptive decline were epilepsy, psychotic disorders, and movement disorders. DISCUSSION: Currently available literature shows limited information on aging in RGNDs, with relatively many reports of young-onset dementia. Longitudinal data may provide insights into converging neurodevelopmental degenerative pathways. We provide recommendations to optimize dementia screening, diagnosis, and research.

Prevalence of swallowing difficulties and associated factors in older people with intellectual disabilities.

BACKGROUND: We investigated the prevalence of swallowing difficulties and associated factors in people with intellectual disability. METHODS: We included people aged 50+ receiving care for people with intellectual disabilities. The Dysphagia Disorder Survey (DDS) was used to assess swallowing difficulties. We determined the agreement between the DDS and swallowing difficulties in medical records. We used logistic regression analyses to explore associated factors. RESULTS: One thousand and fifty people were included. The prevalence of swallowing difficulties was 43.8%. Swallowing difficulties were not reported in the medical records of 83.3% of these cases. Frailty (odds ratio (OR) = 4.22, 95% CI = 2.05-8.71), mobility impairment (OR = 2.50, 95% CI = 1.01-6.19), and mealtime dependency (OR = 3.05, 95% CI = 1.10-8.47) were independently associated with swallowing difficulties. CONCLUSION: Swallowing difficulties are prevalent in older people with intellectual disability but may be under-recognised. Frailty may be a good indicator for population-based screening for swallowing difficulties.

The Effect of Progressive Resistance Exercise Training on Cardiovascular Risk Factors in People with Intellectual Disabilities: A Study Protocol.

Progressive resistance exercise training (PRET) reduces cardiovascular risk factors (CVRF) in the general population. It is unknown if PRET also reduces these risk factors in adults with intellectual disabilities (ID). The aim is to present the protocol of an intervention study that investigates the effect of PRET on CVRF in adults with ID. We will use a repeated time series design with one study group. Adults with mild-to-moderate ID and at least two CVRF are eligible (Netherlands Trial Register, NL8382). During a 12-week baseline period, measurements take place at a 6-week interval. After this, the PRET programme starts for 24 weeks, after which all measurements will be repeated. We will use hierarchical regression models, adjusted for sport activity and medication use, to estimate the effect of PRET. After the intervention, the participants will be followed-up for 12 weeks. We will evaluate factors for successful implementation of exercise in daily life. Primary outcomes are: hypertension, obesity, hypercholesterolemia, diabetes, metabolic syndrome. Secondary outcomes are: physical fitness, sarcopenia, physical activity, activities of daily living, falls, challenging behaviour. If our results show that the PRET programme is effective, it may be a promising non-pharmacological intervention to reduce CVRF in adults with ID.

A Dutch Perspective on Two Health Related Issues Regarding Children and Adolescents with Intellectual Disabilities.

In this opinion article, we want to inspire readers by highlighting recent Dutch developments about two important health related issues regarding the quality of life of children and adolescents with intellectual disabilities. Firstly we focus on the prevention, treatment and reduction of (disability-related) somatic and psychological problems by specialized physicians for people with intellectual disabilities. Secondly, we emphasize the importance of the prevention of adverse childhood experiences and the promotion of protective and compensatory experiences. Subsequently, we stress the need for trauma informed care to support children and adolescents with intellectual disabilities who encounter adverse events. A specialized and multidisciplinary approach is advised as is the need for promoting healthy (family) relations with a focus on (co)regulation and connection as a basis for recovery.

Healthy Ageing and Intellectual Disability study: summary of findings and the protocol for the 10-year follow-up study.

INTRODUCTION: The Healthy Ageing and Intellectual Disability (HA-ID) study is a prospective multicentre cohort study in the Netherlands that started in 2008, including 1050 older adults (aged ≥50) with intellectual disabilities (ID). The study is designed to learn more about the health and health risks of this group as they age. Compared with the amount of research in the general population, epidemiological research into the health of older adults with ID is still in its infancy. Longitudinal data about the health of this vulnerable and relatively unhealthy group are needed so that policy and care can be prioritised and for guiding clinical decision making about screening, prevention and treatment to improve healthy ageing. METHODS AND ANALYSIS: This article presents a summary of the previous findings of the HA-ID study and describes the design of the 10-year follow-up in which a wide range of health data will be collected within five research themes: (1) cardiovascular disease; (2) physical activity, fitness and musculoskeletal disorders; (3) psychological problems and psychiatric disorders; (4) nutrition and nutritional state; and (5) frailty. ETHICS AND DISSEMINATION: Ethical approval for the 10-year follow-up measurements of the HA-ID study has been obtained from the Medical Ethics Review Committee of the Erasmus MC, University Medical Centre Rotterdam (MEC-2019-0562). TRIAL REGISTRATION NUMBER: This cohort study is registered in the Dutch Trial Register (NTR number NL8564) and has been conducted according to the principles of the Declaration of Helsinki.

What is in a name? Definitions of insomnia in people with intellectual disabilities.

BACKGROUND: The reported prevalence of insomnia symptoms in people with intellectual disabilities varies greatly, possibly due to the lack of a common definition. This article provides an overview of the different definitions used and formulates key points for a general definition. METHODS: A literature search was performed. An overview of the definitions used was given and compared to the third edition of the international classification of sleep disorders. RESULTS: The search yielded 16 studies. No uniform definition was used. Terminology and cut-off points of insomnia symptoms differed. Insomnia symptoms were mostly described as night-time problems. A minority of studies incorporated daytime consequences. CONCLUSION: An insomnia disorder entails more than merely night-time complaints and should include daytime consequences. A general definition is warranted. This definition should focus on night-time and daytime insomnia symptoms, incorporate subjective features, and discuss the use of objective measurements and influence of environmental circumstances.

Antipsychotics withdrawal in adults with intellectual disability and challenging behaviour: study protocol for a multicentre double-blind placebo-controlled randomised trial.

BACKGROUND: In people with intellectual disability (ID) and challenging behaviour, antipsychotics (AP) are often used off-label and for a long period. Despite a lack of evidence for efficacy for challenging behaviour and concerns about common and clinically relevant side effects, complete withdrawal often fails. We postulate three possible hypotheses for withdrawal failure: 1. Influence of subjective interpretation of behavioural symptoms by caregivers and family; 2. Beneficial effects from AP treatment on undiagnosed psychiatric illness, through improvement in sleep or a direct effect on behaviour; and 3. Misinterpretation of withdrawal symptoms as a recurrence of challenging behaviour. METHODS: To investigate our hypotheses, we have designed a multicentre double-blind, placebo-controlled randomised trial in which AP (pipamperone or risperidone) are withdrawn. In the withdrawal group, the AP dose is reduced by 25% every 4 weeks and in the control group the dose remains unaltered. Behaviour, sleep, psychiatric disorders, withdrawal symptoms and side effects will be measured and compared between the two groups. If drop-out from the protocol is similar in both groups (non-inferiority), the first hypothesis will be supported. If drop-out is higher in the withdrawal group and an increase is seen in psychiatric disorders, sleep problems and/or behavioural problems compared to the control group, this suggests effectiveness of AP, and indications for AP use should be reconsidered. If drop-out is higher in the withdrawal group and withdrawal symptoms and side effects are more common in the withdrawal group compared to the control group, this supports the hypothesis that withdrawal symptoms contribute to withdrawal failure. DISCUSSION: In order to develop AP withdrawal guidelines for people with ID, we need to understand why withdrawal of AP is not successful in the majority of people with ID and challenging behaviour. With this study, we will bridge the gap between the lack of available evidence on AP use and withdrawal on the one hand and the international policy drive to reduce prescription of AP in people with ID and challenging behaviour on the other hand. TRIAL REGISTRATION: This trial is registered in the Netherlands Trial Register (NTR 7232) on October 6, 2018 ( www.trialregister.nl ).

Are we still in the dark? A systematic review on personal daily light exposure, sleep-wake rhythm, and mood in healthy adults from the general population.

Insufficient light exposure is assumed to be related to a wide array of health problems, though few studies focus on the role of whole-day light exposure in the habitual setting in the development of these health problems. The current review aims to describe the association between personal light exposure in the habitual setting and sleep-wake rhythm and mood in healthy adults from the general population. Five databases (Embase, Medline Epub, Web of Science, PsycINFO, and Google Scholar) were searched in June 2019. The inclusion criteria included: assessment directly of light exposure on the participants for at least one full day; reporting on both individual personal light exposure and outcomes. The quality of the papers was assessed using the Quality Assessment Tool for Observational Cohort and Cross-Sectional Studies of the National Heart, Lung and Blood Institute. The current review followed the PRISMA guidelines. In total, 8140 papers were identified in the database search. Twenty-five papers were eventually included in this review. All included studies were cross-sectional, and individual light exposure was usually measured with a wrist-worn device. Five studies received a "good" quality rating, 16 received a "fair" rating, and the remaining 4 a "poor" quality rating. The overall quality of the included studies was considered low because of the lack of intervention studies and the fact that light exposure was measured on the wrist. Given the low quality of the included studies, the current review can only provide a first exploration on the association between light exposure and sleep-wake rhythm and mood in healthy adults from the general population. Limited evidence is presented for a positive relationship between the amount and timing of light exposure on the one hand and rest-activity rhythm and some estimates of sleep architecture on the other. The evidence on an association between light exposure and circadian phase, sleep estimates, sleep quality, and mood is conflicting. Data from intervention studies are needed to gain insight into the causal mechanism of the relationship between light exposure and sleep-wake rhythm and mood.

Consensus on a conversation aid for shared decision making with people with intellectual disabilities in the palliative phase.

BACKGROUND: Little is known about how to involve people with intellectual disabilities in making decisions about treatment and care in their palliative phase. We aimed to reach a consensus about a shared decision-making (SDM) conversation aid for people with intellectual disabilities, relatives, and healthcare professionals. METHODS: In a Delphi process, an expert panel of 11 people with intellectual disabilities, 14 relatives, and 65 healthcare professionals completed online questionnaires about the relevance and feasibility of a draft conversation aid. RESULTS: In Round 1, components were rated as (very) relevant by 70-98% of participants (M = 87%). In Round 2, after amending the aid in response to feedback, relevance ratings were 67-97% (M = 90%) and feasibility ratings 66-86% (M = 77%). The final version consists of four themes: who are you; illness/end-of-life; making decisions; and evaluating the decision. CONCLUSION: The consensus-based conversation aid is considered sufficiently relevant and feasible to be implemented in practice.

Hair glucocorticoids in adults with intellectual disabilities and depressive symptoms pre- and post-bright light therapy: First explorations.

BACKGROUND: Depressive symptoms and stress are common in adults with intellectual disabilities. Our aim was to explore long-term biological stress levels, assessed by hair cortisol (HairF) and cortisone (HairE) concentrations, in adults with intellectual disabilities and depressive symptoms and to investigate the effects of bright light therapy (BLT) on hair glucocorticoids. METHOD: Scalp hair samples (n = 14) were retrospectively examined at baseline and post-BLT (10.000 and 300 lux). Liquid chromatography-tandem mass spectrometry was used to measure hair glucocorticoids. RESULTS: A significant correlation was found between baseline HairF and depression scores (r = .605, p = .028). Post-intervention HairE levels were significantly increased ([95% CI: 11.2-17.4 pg/mg], p = .003), in particular after dim light (300 lux) ([95% CI: 10.0-18.3 pg/mg], p = .020). CONCLUSIONS: This study showed that retrospectively examining biological levels of stress in adults with intellectual disabilities seems a potentially promising and objective method to gain insight in the stress level of adults with intellectual disabilities.

Determining Frailty in People With Intellectual Disabilities in the COVID-19 Pandemic.

Background: Across the world, frailty is part of the guidelines that are being developed in the COVID-19 pandemic for triaging in crisis situations. The Clinical Frailty Scale (CFS) evaluates the ability to perform daily tasks to identify frail individuals, potentially excluding those from intensive care (IC) treatment. Individuals with intellectual disabilities (ID) experience varying degrees of dependence, distinct from age-related physical deterioration. Using the CFS for triage in crisis situations could potentially unjustifiably exclude individuals with ID from IC treatment. Our objective was to compare the classification of individuals with ID into different frailty categories based on the CFS and the well-studied ID-frailty index and to determine suitability of CFS for evaluation of frailty in individuals with ID during the COVID-19 pandemic. Methods: This retrospective analysis of the observational healthy aging and intellectual disabilities (HA-ID) study included 982 individuals with ID of ≥50 years, who were classified according to the CFS and the ID-frailty index. Results: Of the cohort of 982 older adults with ID, 626 (63.7%) would be classified as moderately frail (CFS score 6), but 92% of this group is not moderately frail according to the ID-frailty index. Furthermore, 199 (20.3%) would be classified as at least severely frail (CFS score 7-9), but 74.9% of this group is not severely frail according to the ID-frailty index. Overall, 730 out of 982 (74.9%) individuals would be incorrectly classified by the CFS as too frail to have a good probability of survival. The ID-frailty index predicts mortality better than the CFS in individuals with ID. Conclusions: Our results show the CFS is not suitable to evaluate frailty in individuals with ID, with potential dramatic consequences for triage and decision-making during the COVID-19 pandemic. We strongly recommend using the ID-frailty index when assessing probability of survival for individuals with ID.

Clinical aspects of a large group of adults with Angelman syndrome.

Descriptions of the clinical features of Angelman syndrome (AS) have mainly been focused on children. Here, we describe the evolution of the clinical phenotypes of AS in adulthood, using clinical data from 95 individuals (mean age 31.6 years, median 29.0 years, range 18-83 years), with genetically confirmed AS. Data was collected through physical examination and inspection of medical records, combined with questionnaires and interviews. Adults with AS experience substantial debilitating health problems. Constipation, reflux, visual problems, scoliosis, behavioral and sleeping problems occurred frequently and require appropriate attention. Epilepsy was reported in 57% of adults, negatively affecting the level of functioning. Non-convulsive status epilepticus was not observed in the adults, however some individuals developed prolonged episodes of rhythmic shaking while awake. A decline in mobility was noted in the majority of adults. A minority of adults with AS showed microcephaly. Taken together, this first phenotypic study of adults with AS to include in person interviews with care-givers and physical examination of patients, including the eldest adult reported to date, provides important insight in the development of the syndrome into adulthood. This knowledge is required to improve care for adult individuals with AS and to evaluate future therapies for this group.

Efficacy and tolerability of brivaracetam in patients with intellectual disability and epilepsy.

Patients with intellectual disability (ID) are often excluded from clinical trials, and little is known about the best approach to treat their epilepsy. Brivaracetam (BRV) is a new antiepileptic drug (AED) for adjunctive treatment in patients with focal-onset seizures with or without secondary generalization. We analyzed the efficacy and tolerability of BRV in patients with ID and epilepsy who either had or had not previously received treatment with levetiracetam (LEV). Data on efficacy and tolerability were retrospectively collected. After the initial start of BRV in our tertiary epilepsy center, we analyzed medical records at 0, 3, 6 and 12 months of follow-up. 116 patients were included (mean age = 34.9 years, 44% female). All had complete data of 3-month follow-up, 76 of 6-month follow-up, and 39 patients of 1-year follow-up. Median starting dose of BRV was 50.0 mg/day and the mean number of concomitant AEDs was 2.6. Seizure reduction and no side effects were reported in more than half of all patients. The most reported side effects were somnolence, dizziness and aggression. Retention rates for BRV were 84.4%, 75.5% and 58.1% after 3, 6 and 12 months, respectively. Seizure reduction and side effects did not differ significantly between the groups with or without previous LEV treatment. We demonstrate that BRV is effective and well tolerated in patients with epilepsy and ID, even in those where previous LEV treatment failed.

Comparison of sleep-wake rhythms in elderly persons with intellectual disabilities and the general population.

BACKGROUND: Sleep problems are common in people with intellectual disabilities (ID), but the knowledge on the natural course of sleep-wake rhythms and sleep problems in elderly persons with ID is limited. In the current study, objectively measured sleep-wake rhythms and the prevalence and severity of sleep problems of elderly persons with ID was compared to that of healthy elderly persons from a large representative sample from the general population. METHODS: Actigraphy data of 501 elderly persons with ID (age 62.02 ± 8.02 years, 48% female) from the Healthy Ageing and Intellectual Disabilities study was compared to the data of 1734 elderly persons from the general population (age 62.24 ± 9.34 years, 53% female) from the Rotterdam Study. Main outcome variables were Interdaily stability (IS) and Intradaily variablitiy (IV), total sleep time (TST), Waking after sleep onset (WASO), Short sleep (TST<6 h), Night waking (WASO >90 min). RESULTS: Elderly persons with ID had less stable sleep wake rhythms than elderly persons from the general population (IS = 0.70 ± 0.17, vs 0.80 ± 0.10 z = -8.00). Their sleep-wake rhythm was also more fragmented (IV = 0.56 ± 0.26 vs 0.42 ± 0.13 respectively, z = 8.00). Elderly persons with ID slept on average 60.09 min longer than elderly persons from the general population, and lay awake 48.28 min longer after sleep onset. Short sleep in elderly persons with ID was less prevalent (20.7% vs 30.2%) but more severe (TST in Short sleep; 5.13 ± 0.80 h vs 5.39 ± 0.50 h, z = -2.76) then in elderly persons from the general population. Night waking was more prevalent (63.0% vs 17.7%) and more severe in elderly persons with ID (WASO in Night waking; 150.39 ± 54.72 min vs 111.60 ± 17.95 min, z = 7.06). CONCLUSION: The differences in sleep-wake rhythms, prevalence and severity of sleep problems between elderly persons with and without ID are marked and possibly explained by medical, psychiatric conditions and lifestyle in elderly persons with ID. Better understanding of sleep in elderly with ID is needed to improve the quality of sleep in this population and to diminish health problems related to a disruption of sleep.

The effect of bright light therapy on depressive symptoms in adults with intellectual disabilities: Results of a multicentre randomized controlled trial.

BACKGROUND: Although a large number of adults with intellectual disabilities have depressive symptoms, non-pharmacological treatments are scarce. The present authors investigated whether bright light therapy (BLT) is effective in decreasing depressive symptoms compared to care as usual. METHODS: This multicentre randomized controlled trial consisted of three study groups (10,000 lux BLT, dim light BLT and a no-BLT group). Participants received BLT for 30 min in the morning (14 consecutive days), additional to their regular care. Primary outcome was as follows: depressive symptoms measured with the ADAMS Depressive Mood subscale 1 week after the end of BLT (same time period in the no-BLT group). RESULTS: Forty-one participants were included in our trial. In both BLT groups, a significant decrease in depressive symptoms was seen. No significant differences were found between 10,000 lux BLT and no-BLT (p = .199) and no significant differences between dim light BLT and no-BLT (p = .451). A minimum amount of side effects and no adverse events were reported. CONCLUSIONS: In both BLT interventions, a decrease in depressive symptoms was seen. With 10,000 lux BLT, depressive symptoms decreased even below the clinical cut-off point, which makes BLT a promising intervention for clinical practice.

Small Steps in Fitness, Major Leaps in Health for Adults With Intellectual Disabilities.

Physical fitness is positively related to health outcomes like morbidity and all-cause mortality, with minimally required cutoff values to generate those health benefits. Individuals with intellectual disability (ID) exhibit very low fitness levels well below those cutoff values. Our novel hypothesis is that even among very unfit, older adults with ID, small changes in fitness translate to major changes in health.

Effectiveness of medication reviews in identifying and reducing medication-related problems among people with intellectual disabilities: A systematic review.

BACKGROUND: Polypharmacy is common in people with intellectual disabilities. Using multiple medication may lead to unintended medication-related problems (MRPs). Medication review may serve as a tool to reduce MRPs. This systematic review assessed the scientific evidence for the effectiveness of medication reviews in identifying and reducing MRPs in people with intellectual disabilities. METHOD: Literature databases were searched up to August 2017. Studies were selected that included the effect of medication reviews on identifying and/or reducing MRPs in people with intellectual disabilities with no restriction of type of medication, age and level of intellectual disabilities. RESULTS: The eight studies that fulfilled the inclusion criteria report that systematic medication reviews appear to assist in the identification and reduction of MRPs. CONCLUSION: There is a lack of studies about the effect of medication reviews on identification and reduction of MRPs, especially health outcomes for people with intellectual disabilities. Further studies with long-term follow-up are needed.

Reliability and validity of the Dutch Anxiety, Depression And Mood Scale in adults aged <50 years with intellectual disabilities.

BACKGROUND: Reliable and valid screening instruments for depression and anxiety are needed for adults with intellectual disabilities. METHODS: Internal consistency (n = 198), inter-rater reliability (n = 41), test-retest reliability (n = 37) and criterion validity (n = 43) were studied in adults aged between 18 and 49 years. Internal consistency was also studied in a sample with epilepsy (n = 98). RESULTS: Internal consistencies of the Dutch ADAMS total scale and subscales were satisfactory to good (α = 0.76-0.92), as well as in the subgroup with epilepsy (α = 0.74-0.88). Inter-rater reliability and test-retest reliability were fair to excellent for the total scale (ICC's: 0.57-0.84) and subscales (ICC's: 0.43-0.86). The criterion validity of the Dutch ADAMS Depressive Mood subscale was good with a sensitivity of 88% (95% CI: 53%-98%) and a specificity of 80% (95% CI: 64%-90%). CONCLUSIONS: Our study shows that the Dutch ADAMS is a reliable and valid instrument for adults aged between 18 and 49 years with intellectual disabilities (and comorbid epilepsy).

Development and applicability of a tool for identification of people with intellectual disabilities in need of palliative care (PALLI).

BACKGROUND: Timely identifying people with intellectual disabilities in need of palliative care is important. Therefore, we developed PALLI: a screening tool for deteriorating health, indicative of a limited life expectancy. Here, we aimed to describe development of PALLI and to explore its applicability. METHOD: We used a five-stage mixed-methods procedure to develop PALLI based on knowledge from practice. For exploring applicability, professionals caring for people with intellectual disabilities completed PALLI for 185 people with intellectual disabilities and provided information on applicability after 5-6 months. RESULTS: The final version of PALLI included 39 questions relevant for people with intellectual disabilities. Applicability was adequate: Most professionals found PALLI relevant and reported no ambiguous questions. Added value of PALLI was reflecting on and becoming aware of the process of decline in health. CONCLUSIONS: PALLI shows promising applicability and has potential as a tool for timely identifying people with intellectual disabilities who may benefit from palliative care.