01.12.2016 | Research | Ausgabe 1/2016 Open Access
Towards onset prevention of cognition decline in adults with Down syndrome (The TOP-COG study): A pilot randomised controlled trial
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Electronic supplementary material
The online version of this article (doi:10.1186/s13063-016-1370-9) contains supplementary material, which is available to authorized users.
Competing interests
The authors declare that they have no competing interests.
Authors’ contributions
SAC was involved with the conception and design of the study, supervised data collection and wrote the funding application, the study protocol and this manuscript. TA was active in recruitment to the study, and revised critically for intellectual content the study protocol and this manuscript. MC directs the laboratory and is responsible for the analyses, and revised critically for intellectual content the funding application, the study protocol and this manuscript. ED managed all pharmacy aspects of the study, critically revised for intellectual content the study protocol and this manuscript. JE was involved with the design of the neuropsychological test battery and revised critically for intellectual content the funding application, the study protocol and this manuscript. NG jointly conducted the statistical analysis and revised critically for intellectual content this manuscript. CH jointly conducted the statistical analysis and revised critically for intellectual content this manuscript. AH contributed to the study design and revised critically for intellectual content the funding application, the study protocol and this manuscript. AJ designed the neuropsychological test battery and revised critically for intellectual content the funding application, the study protocol and this manuscript. AM designed the statistical plan, was responsible for analyses and revised critically for intellectual content the funding application, the study protocol and this manuscript. JM contributed to the study design and revised critically for intellectual content the funding application, the study protocol and this manuscript and helped to analyse the qualitative interviews. HR contributed to the study design and revised critically for intellectual content the funding application, the study protocol and this manuscript. JS was involved with the conception of the study, contribution to the study design and revised critically for intellectual content the funding application, the study protocol and this manuscript. CSi contributed to the development of the study protocol, and this manuscript. CSt acquired the study data and revised critically for intellectual content the study protocol and this manuscript. FS contributed to the study design and revised critically for intellectual content the funding application, the study protocol and this manuscript. All authors read and approved the final version of the manuscript.
Authors’ information
SAC, BSc, MBBS, FRCPsych, MD, is a professor of learning disabilities. TA, MBBS, MRCPsych, is a consultant in learning disabilities psychiatry. MC, BSc, AIMLS, FIMLS, PhD, is a professor of vascular biochemistry. ED, MRPharmS, PhD, is a senior clinical trials pharmacist. JE, BSc, DipClinPsych, PhD, is a professor of applied neuropsychology. NG, BSc, MSc(R), is a biostatistician. CH, BSc, MSc(R), PhD, is a biostatistician. AH, MD, MA, PhD, FRCPsych, is a professor in learning disabilities. AJ, BSc, MPhil (Clin Psychol), PhD, is a professor of learning disabilities. AM, BSc, MSc, PhD, is the Assistant Director of Biostatistics at the Robertson Centre for Biostatistics, University of Glasgow. JM, MBChB, MSc, PhD, FRCGP, is a professor of general practice. HR, BSc, MBBS, FRCPsych, MD, is a reader in neuropsychiatry. JS, MBBS, MA, FRCPEd, FRSPH, is a consultant in general and geriatric medicine and honorary professor of health and ageing. CSi, MBChB, MRCPsych, is an associate specialist in learning disabilities psychiatry. CSt, BSc, MSc, is a research assistant. FS, FRSE, FRCGP, FRCP, is a professor of research and Director of the University of Toronto Practice-Based Research Network (UTOPIAN).
Abstract
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.