The TOP-COG study

• Research type

  Research Study

• Full title

  Towards Onset Prevention of COGnitive decline in adults with Down syndrome (the TOP-COG study)

• IRAS ID

  77898

• Eudract number

  2011-001564-21

• Research summary

  This is a feasibility/pilot study to design a full-scale multi-centre randomised placebo controlled trial (RCT) of daily simvastatin 40mg for the primary prevention of dementia in Alzheimer disease (AD) in adults with Down syndrome. Adults with Down syndrome are at high risk for dementia in AD (40% prevalence =50 years). Trisomy 21 causes Down syndrome; the amyloid precursor protein gene is coded on chromosome 21, so increasing amyloid Ç? (AÇ?) in Down syndrome, which is implicated in AD. Simvastatin slows brain AÇ? deposition, and may delay AD onset, but there has only been one cohort study with Down syndrome adults, and no trials. General population studies are probably not generalisable to Down syndrome, due to genetic physiological differences. Vascular dementias and stroke are rare in Down syndrome adults, who acquire a ??pure? AD. There have been few medication RCTs with intellectual disabled adults, so little available information on likely recruitment rates, and some evidence suggesting differences from general population RCTs. Also, whilst several studies report changes in proxy-reported adaptive functioning over time with Down syndrome adults, little has been reported on the early changes in cognitive decline, or the best instruments to detect decline. Sixty Down syndrome adults aged =50 will be recruited from Greater Glasgow and Clyde, Lothian, and Tayside to this pilot double-blind RCT. They will be randomised to daily simvastatin 40mg or placebo, for 12 months. The study will assess recruitment and retention feasibility and sources, and factors affecting recruitment. It will determine the most sensitive tools to detect early cognitive decline. Between-group differences in cognitive decline will be measured and its variation, to gauge the number who should be recruited in the full-scale RCT. A sub-study will seek views regarding trial participation and randomization. Consent will be taken to store samples for future use and record-linkage.

• REC name

  Scotland A REC

• REC reference

  11/AL/0200

• Date of REC Opinion

  5 Jul 2011

• REC opinion

  Further Information Favourable Opinion