Exploring neurodevelopmental profiles of young people with borderline personality disorder: a feasibility study and clinical research portfolio

Background: Borderline personality disorder (BPD) is the most common of personality disorders presenting in clinical practice. Limited research has been conducted on the potential overlap of neurodevelopmental disorders (NDDs) and personality disorder. However, increasing evidence demonstrates clinical symptom overlap and/or comorbidity between BPD and Attention Deficit Hyperactivity Disorder (ADHD) and Autism Spectrum Disorder (ASD). Aims: The primary aim was to pilot the feasibility of recruitment of young people with BPD to investigate the prevalence of NDDs. The secondary aim was to investigate profiles of young people with BPD with regards to NDDs, emotion regulation, attachment, and adverse childhood experiences (ACEs). Methods: Participants were recruited from a number of mental health teams and services. Data from psychometric assessment measures were collected over two meetings. Descriptive statistics were completed and exploratory analysis conducted. Results: Twenty-nine young people with BPD, aged between 15 and 33, were recruited. Of this group 58% (n = 17) screened positive for ASD and 80% ( n = 23) for ADHD. Twenty-two (76%) of the participants had experienced at least 1 ACE. This pilot study evidenced feasibility of recruitment of young people with BPD, indicating it could be conducted on a larger-scale. The selected psychometric assessment measures were helpful in facilitating a clearer understanding of the neurodevelopmental profile of young people with BPD. Conclusion: Given the importance of early intervention for young people with BPD, understanding the neurodevelopmental profile of these individuals presenting to mental health services may lead to improved long-term outcomes. The high proportion of participants screening positive for NDDs warrants further research

Toward onset prevention of cognitive decline in adults with Down syndrome (the TOP-COG study) : study protocol for a randomized controlled trial

This study is funded by the Chief Scientist Office, Scottish Government Health Department (reference: CZH/4/626). JS is funded by the NHS Lothian R&D Directorate.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 β (Aβ) 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 40 mg 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. TRIAL REGISTRATION: Current Controlled Trials ISRCTN Register ID: ISRCTN67338640 (17 November 2011).Publisher PDFPeer reviewe

Toward onset prevention of cognitive decline in adults with Down syndrome (the TOP-COG study): study protocol for a randomized controlled trial.

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 β (Aβ) 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 40 mg 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. TRIAL REGISTRATION: Current Controlled Trials ISRCTN Register ID: ISRCTN67338640 (17 November 2011).This study is funded by the Chief Scientist Office, Scottish Government Health Department (reference: CZH/4/626). JS is funded by the NHS Lothian R&D Directorate.This is the final published version. It first appeared at http://www.trialsjournal.com/content/15/1/202

Measuring the effects of listening for leisure on outcome after stroke (MELLO):A pilot randomized controlled trial of mindful music listening

Background: Cognitive deficits and low mood are common post-stroke. Music listening is suggested to have beneficial effects on cognition, while mindfulness may improve mood. Combining these approaches may enhance cognitive recovery and improve mood early post-stroke. Aims: To assess the feasibility and acceptability of a novel mindful music listening intervention. Methods: A parallel group randomized controlled feasibility trial with ischemic stroke patients, comparing three groups; mindful music listening, music listening and audiobook listening (control group), eight weeks intervention. Feasibility was measured using adherence to protocol and questionnaires. Cognition (including measures of verbal memory and attention) and mood (Hospital Anxiety and Depression Scale) were assessed at baseline, end of intervention and at six-months post-stroke. Results: Seventy-two participants were randomized to mindful music listening (n = 23), music listening (n = 24), or audiobook listening (n = 25). Feasibility and acceptability measures were encouraging: 94% fully consistent with protocol; 68.1% completing ≥6/8 treatment visits; 80–107% listening adherence; 83% retention to six-month endpoint. Treatment effect sizes for cognition at six month follow-up ranged from d = 0.00 ([−0.64,0.64], music alone), d = 0.31, ([0.36,0.97], mindful music) for list learning; to d = 0.58 ([0.06,1.11], music alone), d = 0.51 ([−0.07,1.09], mindful music) for immediate story recall; and d = 0.67 ([0.12,1.22], music alone), d = 0.77 ([0.16,1.38]mindful music) for attentional switching compared to audiobooks. No signal of change was seen for mood. A definitive study would require 306 participants to detect a clinically substantial difference in improvement (z-score difference = 0.66, p = 0.017, 80% power) in verbal memory (delayed story recall). Conclusions: Mindful music listening is feasible and acceptable post-stroke. Music listening interventions appear to be a promising approach to improving recovery from stroke

Towards onset prevention of cognition decline in adults with Down syndrome (The TOP-COG study): A pilot randomised controlled trial.

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 .This study was funded by the Chief Scientist Office, Scottish Government Health Department (reference: CZH/4/626). JS is funded by the NHS Lothian R&D Directorate. The study was supported by Down Syndrome Scotland, and we thank them, and all members of the Trial Steering Committee and Data Management and Ethics Committee.This is the final version of the article. It first appeared from BioMed Central via https://doi.org/10.1186/s13063-016-1370-

Experiences of stigma and discrimination in borderline personality disorder: a systematic review and qualitative meta-synthesis

No abstract available

Towards onset prevention of cognition decline in adults with Down syndrome (The TOP-COG study). Pilot randomised controlled trial.

Background Dementia is very common in Down syndrome (trisomy 21) adults. Statins may slow brain amyloid ß (Aß, 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). 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 40mg 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 ε4, 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 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%) 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 Intellectual Disabilities battery. Cognitive testing appeared more sensitive than proxy-rated adaptive behaviour, quality of life, or general health scores. Aβ40 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.This study was funded by the Chief Scientist Office, Scottish Government Health Department (reference: CZH/4/626). JS is funded by the NHS Lothian R&D Directorate. The study was supported by Down Syndrome Scotland, and we thank them, and all members of the Trial Steering Committee and Data Management and Ethics Committee.This is the final version of the article. It first appeared from BioMed Central via https://doi.org/10.1186/s13063-016-1370-

MELLO: Study Protocol: A Feasibility Randomised Controlled Trial Of Listening Based Leisure Activities Following Ischemic Stroke

Background and aims: Stroke is the leading cause of disability in older adults. Early post-stroke interventions often focus on physical recovery. Less attention is paid to mood and cognition enhancing interventions that have the potential to improve well-being without the adverse side effects associated with pharmacological interventions. Daily music listening is an accessible and a low cost activity that has been suggested to have a beneficial effect on cognition and mood post stroke. The mechanism of this effect, or if it is reliable, however is not clear. It is speculated that music listening may enhance control of attention in a similar way to mindfulness interventions, that have been demonstrated to be beneficial in the treatment of mood disorders. This study aims to investigate the feasibility and acceptability of a novel intervention combining music listening with brief mindfulness training, within a randomised controlled trial (RCT) context, early post stroke. Method: This is a three-arm, parallel group, single-blind pilot randomised controlled trial (RCT). Individuals with ischemic stroke undergo assessment of mood and cognition (attention and memory) within four weeks post-stroke prior to being randomised to receive an 8-week music listening, mindful music listening, or audiobook listening intervention. Follow-up assessments of mood and cognition are carried out at 3-months and 6-months post-stroke. In addition, a qualitative interview exploring participants’ experience will be completed post intervention. Conclusions: If the mindful music listening intervention is found to be feasible and acceptable, a full scale RCT to investigate its efficacy would be warranted

MELLO: Study Protocol: A Feasibility Randomised Controlled Trial Of Listening Based Leisure Activities Following Ischemic Stroke

Background and aims: Stroke is the leading cause of disability in older adults. Early post-stroke interventions often focus on physical recovery. Less attention is paid to mood and cognition enhancing interventions that have the potential to improve well-being without the adverse side effects associated with pharmacological interventions. Daily music listening is an accessible and a low cost activity that has been suggested to have a beneficial effect on cognition and mood post stroke. The mechanism of this effect, or if it is reliable, however is not clear. It is speculated that music listening may enhance control of attention in a similar way to mindfulness interventions, that have been demonstrated to be beneficial in the treatment of mood disorders. This study aims to investigate the feasibility and acceptability of a novel intervention combining music listening with brief mindfulness training, within a randomised controlled trial (RCT) context, early post stroke. Method: This is a three-arm, parallel group, single-blind pilot randomised controlled trial (RCT). Individuals with ischemic stroke undergo assessment of mood and cognition (attention and memory) within four weeks post-stroke prior to being randomised to receive an 8-week music listening, mindful music listening, or audiobook listening intervention. Follow-up assessments of mood and cognition are carried out at 3-months and 6-months post-stroke. In addition, a qualitative interview exploring participants’ experience will be completed post intervention. Conclusions: If the mindful music listening intervention is found to be feasible and acceptable, a full scale RCT to investigate its efficacy would be warranted