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

Cooper, S.-A. et al. (2014) Toward onset prevention of cognitive decline in adults with Down syndrome (the TOP-COG study): study protocol for a randomized controlled trial. Trials, 15(202), (doi:10.1186/1745-6215-15-202) (PMID:24888381) (PMCID:PMC4061534)

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Abstract

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 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.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Morrison, Professor Jillian and Jahoda, Professor Andrew and Evans, Professor Jonathan and Stiles, Ms Ciara and Cooper, Professor Sally-Ann and McConnachie, Dr Alex and Caslake, Professor Muriel
Authors: Cooper, S.-A., Caslake, M., Evans, J., Hassiotis, A., Jahoda, A., McConnachie, A., Morrison, J., Ring, H., Starr, J., Stiles, C., and Sullivan, F.
College/School:College of Medical Veterinary and Life Sciences > Institute of Cardiovascular and Medical Sciences
College of Medical Veterinary and Life Sciences > Institute of Health and Wellbeing > General Practice and Primary Care
College of Medical Veterinary and Life Sciences > Institute of Health and Wellbeing > Mental Health and Wellbeing
College of Medical Veterinary and Life Sciences > Institute of Health and Wellbeing > Robertson Centre
Journal Name:Trials
Publisher:BioMed Central
ISSN:1745-6215
ISSN (Online):1745-6215
Published Online:03 June 2014
Copyright Holders:Copyright © 2014 Cooper et al.
First Published:First published in Trials 15:202
Publisher Policy:Reproduced under a Creative Commons licence

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Project CodeAward NoProject NamePrincipal InvestigatorFunder's NameFunder RefLead Dept
529271Towards onset prevention of cognitive decline in adults with Down syndromeSally-Ann CooperScottish Executive Health Department (SEHHD-CSO)CZH/4/626IHW - MENTAL HEALTH & WELLBEING