Do cholinesterase inhibitors slow progression of Alzheimer's disease?
In the absence of a cure for Alzheimer's disease (AD), treatment has focused on therapy to provide symptomatic benefits and to slow progression of the disease, so that patients can maintain their independence for as long as possible. New research suggests that rivastigmine, a potent, pseudo-irreversible inhibitor of both acetylcholinesterase (AChE) and butyrylcholinesterase that shows preferential selectivity for the G1 form of AChE, may provide symptomatic and disease progression slowing effects. The drug's pharmacological properties may help to slow the conversion of diffuse, benign amyloid plaques to neuritic plaques associated with clinical dementia. In 'delayed-start' paradigms--open-label extensions of placebo-controlled studies involving mild to moderate AD patients--the treatment effects of rivastigmine on cognitive and non-cognitive outcomes at 52 weeks were even greater than those observed at 26 weeks, and patients who received rivastigmine for the entire 52 weeks had better outcomes than those who received rivastigmine only for the latter 26 weeks (having received placebo for the first 26 weeks during the placebo-controlled phase). These treatment effects were even more robust in patients with moderately severe disease, indicating that the sustained long-term benefits of rivastigmine apply across the continuum of disease severity. The results seen in those patients with mild and moderately severe AD suggest that the progression of AD was being slowed in treated patients and that a disease-modifying effect may have been taking place. The effects of rivastigmine on cognition remain clinically relevant for at least 2 years, with benefits over projected placebo increasing over time. The long-term benefits of rivastigmine have also been reported in behavioural domains of patients with mild to moderate AD for 104 weeks and in patients with the Lewy body variant of AD for 96 weeks. Rivastigmine may slow AD progression, allowing patients to maintain autonomy for longer.
Indiana University School of Medicine, Indianapolis, USA.
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Farlow
D000544:Alzheimer Disease / Q000188:drug therapy*; D002219:Carbamates / Q000627:therapeutic use; D002800:Cholinesterase Inhibitors / Q000627:therapeutic use*; D018450:Disease Progression; D006801:Humans; D018697:Nootropic Agents / Q000627:therapeutic use*; D048448:Phenylcarbamates; D000068836:Rivastigmine
D002219:Carbamates; D002800:Cholinesterase Inhibitors; D018697:Nootropic Agents; D048448:Phenylcarbamates; D000068836:Rivastigmine