Conventional Versus New Treatment: Comparing the Effects of Acetylcholinesterase Inhibitors and N-Methyl-D-Aspartate Receptor Antagonist With Aducanumab

Alzheimer’s dementia (AD) is the most common major neurocognitive impairment and the fifth leading cause of death in older adults in the United States. The diagnosis is clinical; however, laboratory tests and imaging frequently rule out secondary causes of dementia. Unfortunately, the treatment available for AD does not reverse dementia, but it may help improve the symptoms and slow the progression of the disease. The conventional treatment - acetylcholinesterase inhibitor (AChEI) therapy and N-methyl-D-aspartate (NMDA) receptor antagonist - is considered to enhance executive function, overall cognition, and activities of daily living. AChEIs such as donepezil, rivastigmine, and galantamine are approved for mild-to-moderate dementia. Furthermore, memantine, an NMDA receptor antagonist, is authorized for moderate-to-severe dementia. Aducanumab, the newest drug available, is an amyloid-beta (Aβ) monoclonal antibody approved only for mild AD. Treatment with either AChEIs or memantine is more cost-effective than aducanumab and the best supportive care. Aducanumab has particular recommendations with strict monitoring and several adverse effects, including amyloid-related imaging abnormalities. The most common adverse effects of AChEIs and memantine include gastrointestinal symptoms, dizziness, confusion, and headaches. Therefore, monitoring should be performed periodically at the clinician’s discretion for clinical response and tolerability of medication. Conventional therapies are only for symptom management but are still beneficial to patients and caregivers. Unfortunately, at this time, aducanumab’s risks outweigh the benefits with a questionable approval process by the Food and Drug Administration (FDA). However, given the potential disease-modifying capabilities of aducanumab, other disease-modifying options may become available by possibly reducing inflammation, preventing Aβ plaques from clumping, or keeping tau proteins from tangling.