Review Question - QID 106979

This patient's clinical presentation is consistent with Alzheimer's disease (AD) in its earlier stages, which may be improved with an acetylcholinesterase antagonist.

AD is associated with decreased acetylcholine production in the brain, particularly in the nucleus basalis of Meynert. It is a clinical diagnosis that may be confirmed posthumously by the presence of intracellular tangles and extracellular plaque on biopsy. Both acetylcholinesterase (AChE) inhibitors and NMDA receptor antagonists have been used to slow progression of AD, although neither is particularly effective. AChE inhibitors, such as donepezil, galantamine, and rivastigmine should be use in patients with early AD. In contrast, the NMDA receptor antagonist memantine may be more appropriate in patients with late AD.

Winslow et al. discuss the treatment of AD. They note that most clinical trials have found little change in effectiveness between different available AChE inhibitors. In addition, although a Cochrane review found a large improvement in treatment with an AChE inhibitor, compared to placebo, another major systematic review found a much smaller effect size.

Salloway et al. performed 2 double-blind, randomized, controlled trials to evaluate the use of bapineuzumab for treatment of mild to moderate AD. Bapineuzumab is a monoclonal antibody for amyloid beta, the protein found in AD plaques. The authors find no significant difference in clinical outcome with bapineuzumab treatment, compared to placebo.

Illustration A shows typical characteristics of early, middle, and late AD. Illustration B shows a coronal brain section with the nucleus basalis of Meynert indicated with the arrow. Illustration C is a chart detailing common brain locations of several neurotransmitters.

Incorrect Answers:
Answer 1: NMDA receptor antagonists, not agonists are used for treatment of AD.
Answer 2: NMDA receptor antagonists, such as memantine, are used for moderate to severe AD. This patient's main symptom is frequent short-term memory loss, which is characteristic of early AD. Moderate AD typically involves a pervasive memory loss, including forgetting personal information and names of family members.
Answer 4: Dopamine analogs are used to treat Parkinson's disease. Although patients with Parkinson's disease may ultimately experience dementia, motor symptoms typically appear earlier than cognitive symptoms.
Answer 5: Although dopamine antagonists have shown mild benefit in AD, they are contraindicated in elderly people because of increased risk of death.