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

Aim: Statins (3‐hydroxy‐3‐methylglutaryl coenzyme A reductase inhibitors) may slow brain amyloid ß deposition and therefore delay Alzheimer disease onset in adults with Down syndrome (DS). We piloted a trial of simvastatin (a statin). Method: Feasibility/pilot double‐blind randomised controlled trial (RCT) of 12 months simvastatin 40mg versus placebo for primary prevention of dementia in adults with DS 50 years and older. Group allocation was stratified by age, apolipoprotein E epsilon4, and cholesterol level. 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 (QoL). Assessments were prerandomisation and at 12 months. Analysis was on an intention‐to‐treat basis. Results: 181 (78%) of the likely eligible population were identified and 21 recruited (11.6%), from a 3,135,974 base population. Recruitment was highly labour intensive. 62% completed the full year. Regarding cognitive decline, results favoured the simvastatin group. Cognitive testing was more sensitive than proxy‐rated adaptive behaviour, QoL, or general health scores. Conclusion: A full‐scale RCT is feasible. It will need 37% UK population coverage to recruit the required 160 participants.