Contributor: Aaron Lessen, MD Educational Pearls:

The cause of Alzheimer's disease is multifactorial, but the most widely suspected mechanism is the amyloid cascade hypothesis:

• Beta-amyloid proteins accumulate in the central nervous system, forming plaques that impair neuronal function.

In recent years, advances have led to the development of targeted therapies with monoclonal antibodies. These drugs:

• Work by degrading amyloid plaques
• Slow the rate of cognitive decline and disease progression
• Have major side effects, most notably the development of amyloid-related imaging abnormalities (ARIA)
  • ARIA may present as edema, effusion, or microhemorrhages, which are only detectable on MRI
  • Symptoms can include headache, vertigo, or focal neurologic deficits that mimic stroke

For patients presenting to the emergency department with stroke-like symptoms, it is important to consider whether they have a history of Alzheimer's disease and whether they are taking these medications.

• This guides decisions about imaging and treatment:
  • The work-up may require MRI, which can delay thrombolytic or endovascular therapy in patients with true strokeConversely, treating a patient with ARIA using thrombolytics increases the risk of bleeding and other complications

References

1. Ebell MH, Barry HC, Baduni K, Grasso G. Clinically Important Benefits and Harms of Monoclonal Antibodies Targeting Amyloid for the Treatment of Alzheimer Disease: A Systematic Review and Meta-Analysis. Ann Fam Med. 2024 Jan-Feb;22(1):50-62. doi: 10.1370/afm.3050. PMID: 38253509; PMCID: PMC11233076.
2. Ma C, Hong F, Yang S. Amyloidosis in Alzheimer's Disease: Pathogeny, Etiology, and Related Therapeutic Directions. Molecules. 2022 Feb 11;27(4):1210. doi: 10.3390/molecules27041210. PMID: 35209007; PMCID: PMC8876037.
3. Perneczky R, Dom G, Chan A, Falkai P, Bassetti C. Anti-amyloid antibody treatments for Alzheimer's disease. Eur J Neurol. 2024 Feb;31(2):e16049. doi: 10.1111/ene.16049. Epub 2023 Sep 11. PMID: 37697714; PMCID: PMC11235913.

Summarized by Ashley Lyons, OMS3 | Edited by Ashley Lyons and Jorge Chalit, OMS4

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