Until recently, available pharmacologic treatment options for Alzheimer’s disease included acetylcholinesterase inhibitors (e.g., donepezil, rivastigmine, galantamine) and the N-methyl-D-aspartate (NMDA) receptor agonist, memantine. However, since 2023, two amyloid-β monoclonal antibody targeting medications, lecanemab-irmb (brand name Leqembi) and donanemab-azbt (brand name Kisunla), have been approved by the US Food and Drug Administration (FDA) and are available for clinical use. These medications act by binding and removing a key component thought to be a major factor in the development of Alzheimer’s disease: amyloid-β plaques found in brain tissue.  In clinical trials, both medications showed a significant reduction in brain amyloid-β plaque content following treatment, as well as a mild slowing of cognitive decline as evidenced by slower decline from baseline on the Clinical Dementia Rating scale Sum of Boxes (CDR-SB) scores. This resulted in a slowing of functional decline at 18 months as compared to placebo.

These medications are intended for patients with mild cognitive impairment or mild dementia due to Alzheimer’s disease. Early stage is defined as Mini-Mental State Exam (MMSE) scores between 20-28/30 for donanemab, 22-30/30 for lecanemab as well as impairment in episodic memory. Additionally, evidence of amyloid on positron-emission tomography (PET) or by cerebrospinal fluid testing must be demonstrated prior to use. There are no published trials yet regarding the impact of these medications in middle to late-stage Alzheimer’s disease, and these medications do not have indications or approval for use in other types of dementia.

While lecanemab and donanemab are approved for patients with mild cognitive impairment or mild dementia due to Alzheimer’s disease, access to these medications can be challenging due to factors including: 1) drug prescribing safety requirements including neuroradiology expertise for baseline and ongoing MRI monitoring, 2) access to positron emission tomography (PET) imaging and/or cerebrospinal fluid studies to confirm amyloid beta presence, and/or genetic testing, as well as 3) access to infusion centers to administer the medication on a routine basis, and 4) cost of imaging and medication ($26,000 annual price for the drug, up to $82,000 total per patient after required imaging).

Adverse effects of both medications include reactions known as Amyloid-Related Imaging Abnormalities (ARIA), which are further divided into edema (ARIA-E) and microhemorrhage (ARIA-H) subtypes. The edema-events are more common than the microhemorrhage-events, with patients remaining frequently asymptomatic.  ARIA events are more common in patients who are genetically found to have an apolipoprotein E ϵ4 allele, especially those who are homozygous, a known risk factor for development of Alzheimer’s disease.

Research is ongoing to provide more information about these disease modifying treatments for mild cognitive impairment or mild dementia due to Alzheimer’s disease, including benefit, risks, monitoring protocols and overall efficacy.  Understanding the basics of the medications will allow for thorough informed decision-making between medical providers and patients as well as their families.