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Background: Dementia is very common in Down syndrome (trisomy 21) adults. Statins may slow brain amyloid β (Aβ, coded on chromosome 21) deposition and, therefore, delay Alzheimer disease onset. One prospective cohort study with Down syndrome adults found participants on statins had reduced risk of incident dementia, but there are no randomised controlled trials (RCTs) on this issue. Evidence is sparse on the best instruments to detect longitudinal cognitive decline in older Down syndrome adults.Methods: TOP-COG was a feasibility/pilot, double-blind RCT of 12 months simvastatin 40 mg versus placebo for the primary prevention of dementia in Alzheimer disease in Down syndrome adults aged 50 years or older. Group allocation was stratified by age, apolipoprotein E (APOE) ε4 allele status, and cholesterol level. Recruitment was from multiple general community sources over 12 months. Adults with dementia, or simvastatin contraindications, were excluded. Main outcomes were recruitment and retention rates. Cognitive decline was measured with a battery of tests; secondary measures were adaptive behaviour skills, general health, and quality of life. Assessments were conducted pre randomisation and at 12 months post randomisation. Blood Aβ40/Aβ42 levels were investigated as a putative biomarker. Results were analysed on an intention-to-treat basis. A qualitative sub-study was conducted and analysed using the Framework Approach to determine recruitment motivators/barriers, and participation experience.Results: We identified 181 (78 %) of the likely eligible Down syndrome population, and recruited 21 (11.6 %), from an area with a general population size of 3,135,974. Recruitment was highly labour-intensive. Thirteen (62 %) participants completed the full year. Results favoured the simvastatin group. The most appropriate cognitive instrument (regarding ease of completion and detecting change over time) was the Memory for Objects test from the Neuropsychological Assessment of Dementia in Individuals with Intellectual Disabilities battery. Cognitive testing appeared more sensitive than proxy-rated adaptive behaviour, quality of life, or general health scores. Aβ40 levels changed less for the simvastatin group (not statistically significant). People mostly declined to participate because of not wanting to take medication, and not knowing if they would receive simvastatin or placebo. Participants reported enjoying taking part.Conclusion: A full-scale RCT is feasible. It will need 37 % UK population coverage to recruit the required 160 participants. Information/education about the importance of RCT participation is needed for this population.Trial Registration: ISRCTN67338640 . [ABSTRACT FROM AUTHOR]

Background: Depression appears to be more enduring amongst people with intellectual disabilities, suggesting that it is a more chronic problem or more poorly managed in this population. This is not helped by a lack of evidence about the effectiveness of psychological therapies for people who have intellectual disabilities and depression. Behavioural activation, which aims to counteract depression by increasing individuals' level of meaningful activity and their exposure to positive reinforcers, has proven to be as effective as cognitive behavioural therapy in the general population. Given that this therapy makes fewer communicative demands and focuses on activity, it was thought that behavioural activation would be both accessible and apt for people with intellectual disabilities, who are often socially marginalised.Methods/design: This study is a multi-centre single-blind randomised controlled trial of behavioural activation versus a self-help attention control intervention for depression in adults with mild/moderate intellectual disabilities. The study has an internal pilot in one centre, to establish that recruitment can be built up and sustained at the required level, before being rolled out across the other sites. One hundred sixty-six participants will be randomly assigned to the behavioural activation or self-help interventions, which will be delivered to individuals with mild to moderate intellectual disabilities, accompanied by someone who provides them with regular support. Both interventions are manualised and will be delivered over a period of approximately 4 months. The primary outcome measure will be the Glasgow Depression Scale, a self-report measure which is completed at baseline and 4 and 12 months post-randomisation. Secondary outcomes include measures of participants' activity levels, proxy reports of depressive symptoms, and cost-effectiveness.Discussion: The study will provide evidence about the effectiveness of behavioural activation for depression, adapted for people who have mild/moderate intellectual disabilities, and will inform the delivery of psychological therapies to people with intellectual disabilities in practice.Trial Registration: Date trial registered: Nov. 13, 2012; trial registration number: ISRCTN 09753005. [ABSTRACT FROM AUTHOR]

Background Early-onset dementia is common in Down syndrome adults, who have trisomy 21. The amyloid precursor protein gene is on chromosome 21, and so is over-expressed in Down syndrome, leading to amyloid b (Ab) over-production, a major upstream pathway leading to Alzheimer disease (AD). Statins (microsomal 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors), have pleiotropic effects including potentially increasing brain amyloid clearance, making them plausible agents to reduce AD risk. Animal models, human observational studies, and small scale trials support this rationale, however, there are no AD primary prevention trials in Down syndrome adults. In this study we study aim to inform the design of a full-scale primary prevention trial. Methods/Design TOP-COG is a feasibility and pilot double-blind randomized controlled trial (RCT), with a nested qualitative study, conducted in the general community. About 60 Down syndrome adults, aged ≥50 will be included. The intervention is oral simvastatin 40mg at night for 12 months, versus placebo. The primary endpoint is recruitment and retention rates. Secondary endpoints are (1) tolerability and safety; (2) detection of the most sensitive neurocognitive instruments; (3) perceptions of Down syndrome adults and caregivers on whether to participate, and assessment experiences; (4) distributions of cognitive decline, adaptive behavior, general health/quality of life, service use, caregiver strain, and sample size implications; (5) whether Aβ42/Aβ40 is a cognitive decline biomarker. We will describe percentages recruited from each source, the number of contacts to achieve this, plus recruitment rate by general population size. We will calculate summary statistics with 90% confidence limits where appropriate, for each study outcome as a whole, by treatment group and in relation to baseline age, cognitive function, cholesterol and other characteristics. Changes over time will be summarized graphically. The sample size for a definitive RCT will be estimated under alternative assumptions. Discussion This study is important, as AD is a major problem for Down syndrome adults, for whom there are currently no effective preventions or treatments. It will also delineate the most suitable assessment instruments for this population. Recruitment of intellectually disabled adults is notoriously difficult, and we shall provide valuable information on this, informing future studies. [ABSTRACT FROM AUTHOR]

Background: Cognitive behaviour therapy (CBT) is the treatment of choice for common mental health problems, but this approach has only recently been adapted for people with learning disabilities, and there is a limited evidence base for the use of CBT with this client group. Anger treatment is the one area where there exists a reasonable number of small controlled trials. This study will evaluate the effectiveness of a manualized 12-week CBT intervention for anger. The intervention will be delivered by staff working in the day services that the participants attend, following training to act as 'lay therapists' by a Clinical Psychologist, who will also provide supervision. Methods/Design: This is a multi-centre cluster randomized controlled trial of a group intervention versus a 'support as usual' waiting-list control group, with randomization at the level of the group. Outcomes will be assessed at the end of the intervention and again 6-months later. After completion of the 6-month follow-up assessments, the intervention will also be delivered to the waiting-list groups. The study will include a range of anger/aggression and mental health measures, some of which will be completed by service users and also by their day service key-workers and by home carers. Qualitative data will be collected to assess the impact of the intervention on participants, lay therapists, and services, and the study will also include a service-utilization cost and consequences analysis. Discussion: This will be the first trial to investigate formally how effectively staff working in services providing day activities for people with learning disabilities are able to use a therapy manual to deliver a CBT based anger management intervention, following brief training by a Clinical Psychologist. The demonstration that service staff can successfully deliver anger management to people with learning disabilities, by widening the pool of potential therapists, would have very significant benefits in relation to the current policy of improving access to psychological therapies, in addition to addressing more effectively an important and often unmet need of this vulnerable client group. The economic analysis will identify the direct and indirect costs (and/or savings) of the intervention and consider these in relation to the range of observed effects. The qualitative analyses will enhance the interpretation of the quantitative data, and if the study shows positive results, will inform the roll-out of the intervention to the wider community. Trial registration: ISRCTN: ISRCTN37509773 [ABSTRACT FROM AUTHOR]

Background: Art psychotherapy has greater potential for use with adults with mild to moderate learning disabilities as it places less of a burden on verbal interaction to achieve positive therapeutic, psychological, and behavioural goals. The feasibility study objectives include testing procedures, outcomes, validated tools, recruitment and attrition rates, acceptability, and treatment fidelity for manualised interpersonal art psychotherapy., Methods: Adult males and females with mild to moderate learning disabilities will be recruited from four NHS secure hospitals. Twenty patients will be recruited and randomly assigned to one of two treatment groups: fifteen 1-h individual sessions of manualised interpersonal art psychotherapy, or a treatment as usual waiting list control group. The Modified Overt Aggression Scale will be administered to both treatment arms. Four patients will be recruited to a single-case design component of the study exploring the acceptability of an attentional condition., Discussion: This multi-site study will assist in future trial planning and inform feasibility including, procedures, treatment acceptability, therapist adherence, and estimation of samples size for a definitive RCT.

Background: The transition from adolescence to adulthood is a 'high-risk' period for weight gain in the general population. There is speculation that this may also be a risk period for adults with intellectual disabilities; however, there has been no research which has monitored change in health indicators. Since adults with intellectual disabilities have higher rates of obesity and engage in more sedentary behaviour and less physical activity than the general population, there is a need to understand more about the lifestyle behaviours of this population during the transition to adulthood. This protocol paper will provide details of the moving on and feeling good feasibility study, designed for young people with intellectual disabilities., Methods/design: A multi-point recruitment strategy will be used to recruit 30 participants with a mild-moderate level of intellectual disability. The aim of the feasibility study is to examine the feasibility of recruitment, participant retention and the measurement of relevant health behaviour outcomes. The study will assess the feasibility of monitoring weight, diet and physical activity levels in adolescents over a 12-month transitional period from school to adult life. This mixed method study will provide insight into the lives of young people with intellectual disabilities and will examine the use of Walker et al.'s social-ecological approach to promote self-determination specific to lifestyle behaviours, during this transition period. Baseline data will be collected during the final year of school, with follow-up data collection at 6 and 12 months. Anthropometric (weight, height, waist and hip circumference), objective physical activity measures (7-day accelerometer wear) and dietary and choice measures will be collected at each time point to assess the feasibility of measuring diet patterns, food frequency, physical activity and BMI. Furthermore, ten participants will be selected for short semi-structured scoping interviews at baseline and 12-month follow-up, to gain information on psychological, social and environmental factors which might affect behaviour change., Discussion: The outcomes from the feasibility study will aid the development and piloting of a sufficiently powered randomised controlled trial. This would allow us to evaluate the effectiveness and sustainability of a lifestyle behaviour intervention, over a 5-year transition period.