The Lancet Student

Trial and Error: Will a new trial of memantine help to improve symptoms of Alzheimer’s disease in Down’s syndrome? by Thomas Fletcher

This blog was submitted by Tom on 12th January 2012.
Tagged with Alzheimer's disease, Down's syndrome, critical appraisal

Our guest blogger, Thomas Fletcher of 'Why Science isn't Boring', looks at a recent Lancet paper - Memantine for dementia in adults older than 40 years with Down's syndrome (MEADOWS): a randomised, double-blind, placebo-controlled trial.

In our ageing world, neurodegenerative diseases are increasingly an issue. This is particularly a problem for people with Down’s syndrome, where the incidence of Alzheimer’s is very high (nearly 50% in over 60s) and the burden of care is even higher.

An article published in The Lancet has sought to address this issue by trialling the effectiveness of the NMDA-receptor antagonist memantine. Logically, it seems a good choice as an anti- Alzheimer’s drug since high Glutamate concentrations are linked to Alzheimer’s via the cholinergic cell death they are thought to cause. Previous studies have also shown mementine to be effective amongst the general population and in mouse models at improving learning and memory, and the hope was that a successful trial would help to do the same in people with Down’s syndrome.

In order to establish memantine’s effectiveness, the trial looked at its efficacy and safety, asking whether it significantly improved cognitive function compared to a placebo and whether it caused significantly more adverse medical effects compared to a placebo over the course of the 52 week trial.

This trial is a nice one to analyse as it is a classic example of a randomised, double- blind clinical trial. Sorting the participants was done by a computer that placed them in groups either receiving the drug or the placebo. It also helped to eliminate bias by tailoring the categories, ensuring that both had a roughly equal number of each sex, age, and cases of dementia. This was also done behind the researcher’s backs, as was the allocation and distribution of the drug, to keep the trial double-blind and prevent the patients being influenced by the researchers.

The participants were tested for cognitive function and adaptive behaviour after 12 weeks, 26 weeks and 52 weeks into the trial, using executive function scales (DAMES) and adaptive behaviour scales (ABS) to score their ability. These helped to provide numerical data that could be used to compare the two groups easily, and also subject them to statistical analysis.

A quick look at any of the tables and figures in the paper suggests no difference between either of the groups, and the statistical analysis backs this up, with no significant differences between the two at any point during the study. The paper also failed to find any safety concerns. So while memantine seems safe, it has no effect on individuals with Down’s syndrome suffering from Alzheimer’s. But can useful conclusions still be drawn from this paper?

Obviously memantine can be eliminated as a suitable treatment. It also raises questions about how effective our current animal models are if they predict the possibility of a successful treatment that later proves to be ineffective. The trial also suggests caution with using other pharmacological treatments on individuals with complex disorders. So while the trial hasn’t uncovered a new treatment, it has eliminated an ineffective one and shown the way for future research to be directed.

Despite the lack of a breakthrough, we can find grounds for optimism with this study. It shows that clinical trials are possible and can work well with this population, and shows the way forward for future research in the area. Even a trial with a negative result keeps the scientific wheels turning.

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Thomas Fletcher was born in London. He graduated from UCL with a BSc in Biomedical Sciences having specialised in Psychopharmacology  and Neuroscience . He writes the blog ‘Why Science isn’t Boring’ which simplifys new research for non-scientists.