"Combination Therapy" for Alzheimer's Disease

Contributed by: Michael Rafii, M.D., Ph.D - Director of the Memory Disorders Clinic at the University of California, San Diego.

As readers of this blog will recall, two types of medications have received FDA approval for Alzheimer’s treatment. Cholinesterase inhibitors have been available since the mid-1990s and act by inhibiting the breakdown of the neurotransmitter acetylcholine. The drug memantine, which received FDA approval in 2003, is the first of a second class of agents that modulate the actions of the amino acid glutamate and is often used in combination with cholinesterase inhibitors (CIs) in later stages.

Researchers were recently able to conduct a study by analyzing data on patients treated at the MGH Memory Disorders Unit since 1990, including 144 who did not receive any pharmaceutical treatment, 122 treated with a CI alone and 116 who received both a CI and memantine from the outset. As part of their regular treatment, every six months patients received standardized assessments of both cognitive abilities and how well they carried out daily activities.

The results showed significant differences in the rate of symptom progression among all three groups – with the smallest level of decline in those receiving combination therapy. While there was an average of two and a half years’ worth of data on the study participants, the researchers analyzed the information with a statistical model that predicted probable outcomes for up to four years. Although the model’s projection of future benefits is conservative, it predicted that the longer patients kept receiving combination therapy, the smaller their rate of decline would become, suggesting that treatment might even protect brain cells from further damage, a possibility needing further investigation.

Some physicians have started prescribing patients CIs and Namenda combination therapy at the start of therapy to see if these results in fact hold-up.

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