Review of Donanemab and Lecanemab in Mild Dementia Stage of Alzheimer's Disease: Progress and Challenges.

Abstract

Alzheimer's disease (AD) is a progressive neurodegenerative disorder marked by cognitive decline and functional impairment, primarily driven by the accumulation of amyloid-beta (Aβ) plaques and tau tangles. Historically, treatments have focused on symptomatic relief; however, recent therapeutic advances have focused on disease-modifying monoclonal antibodies (mAbs), notably lecanemab and donanemab, which target Aβ pathology in early-stage AD. This review explores the clinical efficacy, safety profile, and limitations of lecanemab and donanemab, emphasizing key findings from the CLARITY-AD and TRAILBLAZER-ALZ 2 trials. In these studies, lecanemab was shown to slow cognitive decline by 27% over 18 months, while donanemab achieved a 28.9% reduction over 76 weeks, with the greatest benefits observed in patients presenting with lower baseline tau pathology.Despite these promising outcomes, challenges remain, including possible reduced efficacy in women based on subgroup analyses of trial data, racial disparities in trial representation, adverse effects such as amyloid-related imaging abnormalities (ARIA), and substantial cost and accessibility barriers. This review underscores the need for more inclusive research, personalized treatment strategies, and continued exploration of AD's complex pathology beyond amyloid clearance.