Memantine is licensed for treating patients with moderate-to-severe Alzheimer's disease (AD). However, a study published Online First by The Lancet shows that the drug is ineffective for AD patients with Down's Syndrome aged 40 years and over. The study is written by Professor Clive Ballard, Wolfson Centre for Age-Related Diseases at King's College London, UK, and colleagues.
Clinically significant AD-like pathological features develop in all people with Down's syndrome by 40 years of age. Almost 40% of people with Down's syndrome who are 60 years or older have a diagnosis of dementia, although diagnosis is not straightforward because of an absence of validated approaches for people with intellectual disabilities. Dementia in Down's syndrome is a key clinical challenge, especially as people with Down's syndrome live longer than they used to, with a high proportion of individuals living to 60 years or beyond. Despite the introduction of antenatal screening in the UK in 1990, the incidence of Down's syndrome had decreased by only 1% by 2008.
Promising findings were reported in two studies of memantine in a Down's syndrome model in mice. Both studies showed improvements in cognitive function and AD neuropathology. This new study enrolled adults (>40 years) with Down's syndrome, and with or without AD, at four learning disability centres in the UK and Norway.
Participants received memantine (88 patients) or placebo (85) for 52 weeks, with the randomisation balanced according to sex, dementia, age group, total Down's syndrome attention, memory, and executive function scales [DAMES] score, and centre. The primary outcome was change in cognition and function, measured with DAMES scores and a standard assessment tool called the adaptive behaviour scale (ABS).
Both groups declined in cognition and function but rates did not differ between groups for any outcomes. 10 (11%) of 88 participants in the memantine group and six (7%) of 85 controls had serious adverse events. Five participants in the memantine group and four controls died from serious adverse events.
Prof Ballard says: "Memantine is not an effective treatment in this group of patients. We believe that this robust finding will have implications for clinical practice and research strategy in the future. Specifically, therapies that are beneficial for people with Alzheimer's disease are not necessarily effective for the treatment of cognitive impairment or dementia in the context of Down's syndrome."
Dr Anne Corbett, Research Manager at Alzheimer's Society (UK), and co-author adds*: "So little is known about the best way to treat dementia in people with Down's Syndrome. Further investment is urgently needed to develop treatments that are effective in this important group of people."
In a linked Comment, Professor Gill Livingston and Dr Andre Strydom, Unit of Mental Health Sciences, University College London, UK, say that due to the complex genetics behind Down's Syndrome, "amelioration of associated pathology [of Alzheimer's Disease in Down Syndrome] will probably not result from one drug, but will need a complex combination of treatments. Researchers need a far greater understanding of the neurobiology of Down's syndrome to design such treatments."
They add: "Despite these issues, there is optimism that the cognitive problems and neurodegeneration of Down's syndrome, which were previously regarded as intractable, can be improved with pharmacological treatments."
Professor Clive Ballard, Wolfson Centre for Age-Related Diseases at King's College London, UK. T) 44-20-7848-6568 E) clive.ballard@kcl.ac.uk
For Dr Anne Corbett, Research Manager at Alzheimer's Society (UK)please contact Lynsey Roberts, Press Office. T) 44-207-423-3606 E) lynsey.roberts@alzheimers.org.uk
Professor Gill Livingston, Unit of Mental Health Sciences, University College London, UK T) 44-7717156977 E) G.Livingston@ucl.ac.uk
*note to editors: quote direct from Dr Corbett, not found in text of Article
Journal
The Lancet