Lecanemab Works in Real-World Memory Clinics With Manageable Safety Profile

Alzheimer's disease remains one of the leading causes of death and disability worldwide, and lecanemab—the first disease-modifying treatment to receive traditional FDA approval in July 2023—represents a paradigm shift in care. However, moving from tightly controlled clinical trials to real-world practice raises critical questions about feasibility, safety, and appropriate patient selection. This retrospective study from Washington University's Memory Diagnostic Center (MDC) offers the most detailed real-world dataset yet on lecanemab use in clinical practice.

The study enrolled 234 consecutive patients with early symptomatic Alzheimer's disease (encompassing MCI, very mild dementia, and mild dementia) who began lecanemab treatment between August 2023 and October 2024. Patients received lecanemab at 10 mg/kg intravenously every two weeks, following FDA label guidance and appropriate-use recommendations with occasional exceptions. A dedicated multidisciplinary infrastructure—including biomarker testing, PET or CSF amyloid confirmation, regular MRI monitoring, and infusion coordination—was established before treatment began. The study assessed infusion-related reactions, ARIA (both edema/effusion [ARIA-E] and hemorrhage/hemosiderin deposition [ARIA-H]), and treatment withdrawal.

Infusion-related reactions occurred in 87 patients (37%), consistent with or slightly higher than clinical trial rates, but were predominantly mild and manageable. Of the 194 patients who received at least 4 infusions and had monitoring MRIs, 42 (22%) developed ARIA during an average follow-up of 6.5 months. ARIA-E with or without ARIA-H occurred in 29 patients (15%), while isolated ARIA-H appeared in 13 patients (6.7%). Symptomatic ARIA developed in 11 patients (5.7%), with 2 patients (1.0%) experiencing clinically severe symptoms. Critically, no patients died or developed macrohemorrhages. Overall, 23 of 234 patients (9.8%) withdrew from treatment; only 10 (4.3%) withdrew specifically due to ARIA.

One of the most clinically significant findings was the striking difference in symptomatic ARIA rates by disease stage. Patients with mild dementia experienced a 27% rate of symptomatic ARIA, compared to just 1.8% among those with MCI or very mild dementia. This differential strongly supports the recommendation to prioritize treatment in earlier disease stages, where both the benefit-risk ratio appears more favorable and the cognitive reserves may offer some buffer against ARIA-related symptoms. Patients with pre-existing microhemorrhages or superficial siderosis (23% of the at-risk group) also warrant heightened vigilance.

The study demonstrates that a well-resourced academic specialty memory clinic can successfully implement lecanemab therapy at scale, treating 234 patients in just 14 months. The infrastructure investments—including dedicated nursing staff, MRI monitoring protocols, biomarker-confirmed eligibility, and close clinical follow-up—appear essential to managing adverse events safely. While these results are encouraging, they reflect a single academic center with considerable expertise, and the safety profile may differ in community settings with less specialized infrastructure.