Recent randomized clinical trials have focused on three agents aimed at treating early Alzheimer’s disease (AD), particularly with donanemab, aducanumab, and lecanemab. These trials were primarily centered around their ability to reduce amyloid deposition as indicated by positron emission tomography (PET) imaging. Donanemab’s trial, TRAILBLAZER-ALZ, demonstrated a notable reduction in amyloid levels and a marginal improvement in the Integrated Alzheimer’s Disease Rating Scale, though this did not significantly impact most secondary cognitive measures.

Aducanumab, assessed in the EMERGE and ENGAGE trials, showed varying results possibly due to mid-study protocol amendments and early termination of the trials. Lecanemab, evaluated in the CLARITY-AD trial, showed both a significant reduction in amyloid on PET scans and improvements in cognitive assessments, though it was associated with serious cardiovascular adverse events. Each of these agents demonstrated the potential for amyloid clearance and some degree of cognitive benefit, but concerns remain about their clinical significance, safety profiles, and long-term benefits, with ongoing extended studies hoping to provide further insights.

Reference: Edwards M, Corkill R. Disease-modifying treatments in Alzheimer’s disease. J Neurol. 2023;270(4):2342-2344. doi:10.1007/s00415-023-11602-8