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.

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.

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.

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 ).

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.