Antiamyloid treatment for dementia: concerns outweigh hopes

Area of Science:

• Neurology
• Neuroscience
• Immunology

Background:

• Alzheimer's disease (AD) is a leading cause of dementia.
• The role of amyloid pathology in dementia is complex and multifactorial.
• Emerging treatments involve monoclonal antibodies (mAbs) targeting amyloid.

Purpose of the Study:

• To review the association between Alzheimer pathology and dementia.
• To evaluate the efficacy and safety of amyloid-targeting mAbs in treating dementia and mild cognitive impairment (MCI).

Main Methods:

• Literature review of studies on Alzheimer pathology, dementia, and mAb treatments.
• Analysis of clinical trial data for mAbs like Aducanumab, Lecanemab, and Donanemab.
• Assessment of benefits, risks (e.g., ARIA), and cost-effectiveness.

Main Results:

• Alzheimer pathology accounts for less than 40% of dementia risk when other pathologies (vascular, Lewy Body, TDP-43) are considered.
• Amyloid-targeting mAbs demonstrated modest benefits, potentially influenced by bias.
• Amyloid-related imaging abnormalities (ARIA) are a common and serious side effect.
• Treatment and assessment costs are substantial relative to observed benefits.

Conclusions:

• The role of mAbs in Alzheimer's dementia treatment remains uncertain.
• Further research is necessary to determine the long-term benefits and risks of these therapies.