Even though memantine is licensed to treat patients with moderate-to-severe Alzheimer’s disease (AD), a study published Online First in The Lancet reports that the drug is not effective for AD patients with Down’s syndrome who are aged 40 years and older.

All individuals with Down’s syndromes develop clinical important AD-like pathological features by the time they are 40 years old, with almost 40% being diagnosed with dementia by the age of 60 years or more. The diagnosis is somewhat complicated as there are no validated diagnostic approaches for those suffering from intellectual disabilities.

Down’s syndrome individuals with dementia represent a major clinical challenge given that the life expectancy of Down’s syndrome patients has increased from what it used to be, with a large proportion living to 60 years and older. Even though in the UK antenatal screening was introduced in 1990, by 2008 the prevalence of Down’s syndrome has still only decreased by 1%.

Two studies of memantine have demonstrated promising results in a Down’s syndrome model in mice, with both studies revealing improvements in cognitive function and AD neuropathology. In the new study, the researchers recruited Down’s syndrome adults aged 40 years or over with or without AD, at four learning disability centers in the UK and Norway.

For the duration of 12 months the researchers administered 88 patients with memantine or 85 patients with placebo. The randomized study was adjusted for variables, such as dementia, sex, age group, total Down’s syndrome attention, memory, the patients’ executive function scales [DAMES] score, and by learning disability center. The researchers measured the primary outcome defined as change in cognition and function with DAMES scores and a standard assessment tool known as the adaptive behavior scale (ABS).

The findings revealed that cognition and function in both groups declined, yet rates for any outcomes were no different between groups. The researchers reported serious adverse events in 10 out of 88 participants or 11% in the memantine group, and in 6 from 85 or 7% of patients in the control group with 5 deaths in the memantine group and 4 deaths in the control group.

According to Prof. Ballard:

“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 supports Prof Ballards view, saying:

“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 at the Unit of Mental Health Sciences at University College London, UK, state in an associated comment that due to Down’s syndrome complex genetics:

“..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. 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.”

The study was led by Professor Clive Ballard at the Wolfson Centre for Age-Related Diseases at King’s College London in the UK and his team.

Written by Petra Rattue