Memantine in Moderate-to-severe Alzheimer's Disease
Memantine in Moderate-to-severe Alzheimer's Disease
Alzheimer's disease (AD) is the most common cause of dementia. It is a progressive neurodegenerative disorder resulting in cognitive and behavioural impairment of sufficient severity to markedly interfere with social and occupational functioning. The prevalence of AD increases steadily after the age of 65, with an estimated prevalence of approximately 50% in patients aged 85 or older.1-2 Moreover, as the population ages, the proportion of the population affected by AD is predicted to increase dramatically.3 AD is not only a heavy burden for the patient but is also responsible for making the patient dependent on his family or the community.
Current pharmacotherapy is focused on delaying the symptomatic progression of AD. Although the cause of the disease remains unknown, acetylcholine deficiency, within a complex milieu of neurotransmitter changes in the brain, has been shown to play a role in AD.4-5 By inhibiting the degradation of acetylcholine released by presynaptic cholinergic neurons, cholinesterase inhibitors increase the amount of acetylcholine available for neurotransmission. Accordingly, cholinesterase inhibitors (ChEIs) have emerged as the treatment of choice for mild-to-moderate AD.
Donepezil, rivastigmine and galantamine represent the main category of ChEIs shown to be effective with an acceptable tolerability profile. Rivastigmine, donepezil and galantamine have demonstrated improvements in cognition, general clinical impression, activities of daily living (ADL) and behavioural symptoms.6 ChEIs share common cholinergic-mediated side effects. The most common cholinergic side effects include nausea, vomiting and diarrhoea; this is more common with initiation and dose titration and may lead to drug withdrawal in some cases.
However, slow titration of ChEIs to therapeutic doses may alleviate many of these symptoms since patients tend to develop tolerance to these gastrointestinal symptoms.7 Currently, there is little evidence to recommend one ChEI over another. In the mild-to-moderate AD population, ChEI therapy should be started early and there are emerging data that efficacy extends to the late stages of the disease.
Moderate-to-severe Alzheimer’s Disease
As AD progresses to the moderate-to-severe stages of the illness, patients becoming increasingly dependent on care from members of their family or care workers.
While emerging data suggest that the efficacy of the ChEIs extends to the late stages of AD, only one drug has been licensed for the treatment of moderate-to-severe AD. Memantine was recently licensed in a number of European countries for use in the moderate-to-severe AD population. It is a non-competitive antagonist at N-methyl-Daspartate (NMDA) receptors.
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