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

Abstract

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.

FDG PET (and MRI) for Monitoring Immunotherapy in Alzheimer Disease

“…What was observed was a deterioration 2.5% less in treated patients on the Clinical Dementia Rating-Sum of Boxes Scale (range, 0–18, with higher scores indicating greater impairment) compared with placebo patients, 9 or approximately 30% of what is considered clinically meaningful on this scale in patients with various stages of AD 22 . None of the minor deteriorations with donanemab and lecanemab exceeded those known from conventional AD therapy with anticholinergic/memantine medication 23,24 …”

“…22 None of the minor deteriorations with donanemab and lecanemab exceeded those known from conventional AD therapy with anticholinergic/memantine medication. 23,24 In contrast to the minimal clinical changes, several trials reported large dose-dependent decreases in cerebral amyloid burden according to amyloid PET, of 27%, 85%, and 55% with aducanumab, 8 donanemab, 16 and lecanemab, 9 respectively. This raises doubts not only about the validity of the amyloid hypothesis but also about the validity of the measurement methods used.…”

“… 22 None of the minor deteriorations with donanemab and lecanemab exceeded those known from conventional AD therapy with anticholinergic/memantine medication. 23 , 24 …”

Photobiomodulation in Alzheimer’s Disease—A Complementary Method to State-of-the-Art Pharmaceutical Formulations and Nanomedicine?

“…Adverse effects during aducanumab administration are numerous and could be suggested by MRI images that can objectify the presence of amyloid-related imaging abnormalities of effusion (ARIA-E) and amyloid-related imaging abnormalities of hemorrhagic events (ARIA-H) expressed clinically by the state of mental alteration, confusion, delirium, disorientation, dizziness, headache, nausea, convulsions, vertigo, visual disturbances, with more frequent symptoms in apolipoprotein E4 carriers, advanced age, people with previous microhemorrhages, cardiovascular risk factors, etc. [ 127 , 157 , 158 ].…”

Editorial: Therapeutic neuromodulation for aging-related disorders associated with the autonomic nervous system

“…Currently there are limited FDA approved pharmacological treatment to slow the progression of this impairment. The off-label medicines acetylcholinesterase inhibitors and N-methyl-D-aspartate receptor antagonists unfortunately induce side effects like gastrointestinal symptoms, confusion, dizziness, and headaches in these patients (Chin et al, 2022 ). Newly approved treatment, Leqembi can cause headaches, confusion, dizziness, and intracranial hemorrhage and edema.…”