Fast Five Quiz: Alzheimer's Disease Management

Jasvinder P. Chawla, MD, MBA; Shaheen E. Lakhan, MD, PhD, MS, MEd


August 22, 2023

The currently approved pharmacologic treatments for Alzheimer's disease are cholinesterase inhibitors (ChEIs), partial N-methyl-D-aspartate (NMDA) receptor antagonists, and anti-amyloids.

Past research demonstrated a lack of acetylcholine (Ach) in the hippocampus and neocortex in patients diagnosed with Alzheimer's disease. ChEIs prevent the breakdown of ACh, which may slow cognitive and functional decline. ChEIs also alleviate the noncognitive symptoms of Alzheimer's disease, including agitation, wandering, and socially inappropriate behavior. The ChEIs include donepezil, galantamine, and rivastigmine.

Adverse effects associated with ChEIs include nausea, vomiting, diarrhea, and dizziness; these agents can also cause symptomatic bradycardia, leading to syncope and fall-related injuries. However, many of these adverse effects can be mitigated through slow up-titration to the desired maintenance dose, or by using the transdermal route.

The partial NMDA receptor antagonist memantine is indicated for treating patients with moderate to severe Alzheimer's disease. Memantine is believed to prevent further nerve damage by inhibiting intracellular calcium accumulation. Common side effects of memantine include dizziness, headache, and confusion.

Lecanemab, a humanized immunoglobulin G1 monoclonal antibody, was approved by the US Food and Drug Administration in July 2023 for individuals with early Alzheimer's disease. This approval was based on the results of the phase 3 Clarity AD study, in which lecanemab reduced markers of amyloid and resulted in moderately less decline in measures of cognition and function than placebo at 18 months.

In addition, aducanumab, another monoclonal antibody that targets amyloid beta, is approved for treatment of early Alzheimer's disease. Patients receiving aducanumab had significant dose- and time-dependent reductions of amyloid beta plaques. Continued use and full approval will require verification of its clinical benefits in postapproval studies.

Another monoclonal antibody has recently completed phase 3 clinical trials in individuals with early symptomatic Alzheimer's disease and amyloid and tau pathology. Studies show that donanemab significantly slows clinical progression after 1.5 years among trial participants.

Carbidopa/levodopa/entacapone is used to treat Parkinson's disease; beta blockers and 5-HT1 receptor agonists are used to treat migraine headache; and calcium channel blockers (CCBs) and angiotensin II receptor blockers are used to treat hypertension. None of these drugs is useful for treating Alzheimer's disease.

Learn more about pharmacologic treatment for Alzheimer's disease.


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