Recent developments in the drug treatment of Alzheimer's disease

Abstract

Alzheimer's disease (AD) is a chronic neurodegenerative disorder with an impact on public health which continues to increase with the increasing longevity of the population. The disease is characterised clinically by a progressive loss of cognitive and behavioural function. These deficits are thought to result from decreased cholinergic transmission; therefore, restoring cholinergic function has been the main focus in the development of drugs for AD. Several pharmacological approaches to enhancing cholinergic function have been developed for symptomatic or palliative therapy of AD. Although these strategies have resulted in modest cognitive and behavioural improvements in patients with AD, they do not address the underlying progression of the disease. New strategies will be required to slow, stop or reverse the effects of neurodegeneration in AD. A number of potential therapies are currently under investigation, including estrogen replacement, anti-inflammatory agents, free radical scavengers and antioxidants, and monoamine oxidase-B (MAO-B) inhibitors. The evidence for a protective effect of estrogens or nonsteroidal anti-inflammatory drugs (NSAIDs) is controversial, and largely based on retrospective studies. More controlled prospective studies are needed to definitively demonstrate the benefits of long term estrogen or NSAID use in the prevention of AD. Free radical scavengers/antioxidants such as idebenone, and selective prevention MAO-B inhibitors such as lazabemide are well tolerated, but require additional studies in order to demonstrate preventative effects. In addition, other approaches, such as anti-amyloid treatments that affect beta-amylase secretion, aggregation and toxicity, appear promising; treatments that hinder neurofibrillary tangle construction and nerve growth factor (NGF) induction are in the very early stages of development.