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

被引：12

作者：

Cooper, Sally-Ann ^{[1
]}

Ademola, Temitope ^{[2
]}

Caslake, Muriel ^{[3
]}

Douglas, Elizabeth ^{[4
]}

Evans, Jonathan ^{[1
]}

Greenlaw, Nicola ^{[5
]}

Haig, Caroline ^{[5
]}

Hassiotis, Angela ^{[6
]}

Jahoda, Andrew ^{[1
]}

McConnachie, Alex ^{[5
]}

Morrison, Jill ^{[7
]}

Ring, Howard ^{[8
]}

Starr, John ^{[9
]}

Stiles, Ciara ^{[1
]}

Sirisena, Chammy ^{[10
]}

Sullivan, Frank ^{[11
,12
]}

机构：

[1] Univ Glasgow, Gartnavel Royal Hosp, Mental Hlth & Wellbeing Grp, Inst Hlth & Wellbeing, Adm Bldg 1055,Great Western Rd, Glasgow G12 0XH, Lanark, Scotland

[2] Inverurie Hosp, Community Learning Disabil Psychiat, Gatehouse, Inverurie AB51 3UL, Scotland

[3] Univ Glasgow, Western Infirm, Inst Cardiovasc & Med Sci, McGregor Bldg,2nd Floor, Glasgow G11 6NT, Lanark, Scotland

[4] Res & Dev NHS Greater Glasgow & Clyde, 1st Floor Tennent Inst,Western Infirm Church St, Glasgow G11 6NT, Lanark, Scotland

[5] Univ Glasgow, Robertson Ctr Biostat, Boyd Orr Bldg, Glasgow G12 8QQ, Lanark, Scotland

[6] UCL, Bloomsbury Campus,Charles Bell House, London W1W 7EY, England

[7] Univ Glasgow, Gen Practice & Primary Care, Inst Hlth & Wellbeing, 1 Horselethill Rd, Glasgow G12 9LX, Lanark, Scotland

[8] Univ Cambridge, Dept Psychiat, Douglas House,18b Trumpington Rd, Cambridge CB2 2AH, England

[9] Alzheimer Scotland Dementia Res Ctr, 7 George Sq, Edinburgh EH8 9JZ, Midlothian, Scotland

[10] Scottish Borders Learning Disabil Serv, Church St, Earlson TD4 6HR, England

[11] Univ Toronto, North York Gen Hosp, Gordon F Cheesbrough Res Chair, 4001 Leslie St, Toronto, ON M2K 1E1, Canada

[12] Univ Toronto, North York Gen Hosp, UTOPIAN, 4001 Leslie St, Toronto, ON M2K 1E1, Canada

来源：

TRIALS | 2016年 / 17卷

关键词：

Alzheimer disease; Dementia; Down syndrome; Neuropsychology; Primary prevention; Simvastatin; Statin; MODERATE ALZHEIMER-DISEASE; INCIDENT DEMENTIA; STATIN USE; INTELLECTUAL DISABILITY; CHOLESTEROL LEVEL; RISK; PEOPLE; ASSOCIATION; POPULATION; IMPAIRMENT;

D O I：

10.1186/s13063-016-1370-9

中图分类号：

R-3 [医学研究方法]; R3 [基础医学];

学科分类号：

1001 ;

摘要：

Background: Dementia is very common in Down syndrome (trisomy 21) adults. Statins may slow brain amyloid beta (A beta, 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) epsilon 4 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 A beta 40/A beta 42 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. A beta 40 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.

引用

页数：16