Monday, July 23, 2012

Memantine Is Ineffective At Treating Alzheimer's Disease In Patients With Down's Syndrome

Though commonly used to treat patients with moderate-to-severe Alzheimer's disease (AD), the anti-dementia drug Memantine - trade name Namenda - has been labeled as ineffective for treating AD patients with Down's Syndrome over the age of 40. The finding comes from a publication by The Lancet written by Professor Clive Ballard, Wolfson Centre for Age-Related Diseases at King's College London, UK, and colleagues.

Pathological features similar to those found among Alzheimer's disease patients are evident in all Down's syndrome patients above the age of 40. As a key clinical challenge, dementia has become increasingly common in Down's patients - as they are living longer than before - with dementia being diagnosed in over 40% of such patients over 60.

Two previous studies of memantine in a Down's syndrome model in mice showed encouraging results. They both found that the medication enhanced neuropathology and cognitive function. To further our understanding on the effect the drug has on human's with Down's, a new study enrolled Down's syndrome patients over the age of 40, some with and some without AD, across four learning disability centers in the UK and Norway.

The 52 week-long study involved two groups of patients, a group of 88 taking memantine and another group of 85 taking the placebo. Selection of the participants across the two groups was balanced in accordance to memory, sex, age group, executive function scales [DAMES] score, dementia and Down's syndrome attention. Assessment was based on evaluating the change in cognition and function. They did so by measuring DAMES scores and using a standard assessment tool called the adaptive behaviour scale (ABS).

Cognition and function dropped for both groups with little disparity between the two rates. Serious adverse events were recorded in 11% of the patients - 10 out of 88 - on memantine and 7% of the controls - 6 out of 85. Of these events, five people died in the memantine group and four from the control group.

Prof Ballard noted that the "robust" finding has serious implications for research strategy and clinical practice in the future, he adds:

"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."


Co-author and Research Manager at Alzheimer's Society (UK), Dr Anne Corbett, 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."


Professor Gill Livingston and Dr Andre Strydom, Unit of Mental Health Sciences, University College London, UK say that the..:

"..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 conclude

"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."

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