Real-world lecanemab data show ARIA risks and limited cognitive evidence

A systematic review and meta-analysis of 37 real-world studies involving people with Alzheimer’s disease found that lecanemab was associated with amyloid-related imaging abnormalities (ARIA) in 15.1% of cases, while the available evidence was insufficient to confirm cognitive benefit. The synthesis, reported in the Journal of Neurology, examined treatment outside controlled trial settings and pooled outcomes including ARIA, discontinuations, infusion-related reactions, serious adverse events, cognitive tests and amyloid PET.

Researchers searched PubMed, Embase and Web of Science through October 1, 2026, for real-world studies of lecanemab in Alzheimer’s disease. The investigators used random-effects models with restricted maximum likelihood and Hartung–Knapp adjustment, and conducted subgroup analyses based on region, APOE ε4 genotype, baseline Clinical Dementia Rating score, microhemorrhage and deep white matter hyperintensity burden. Sensitivity analyses included leave-one-out analyses, Egger’s test and scenario-based analyses for overlapping cohorts. For each outcome, the largest dataset was retained when cohorts overlapped, with peer-reviewed reports prioritized.

Pooled incidence was 6.5% for ARIA-E and 11.5% for ARIA-H, while symptomatic ARIA occurred in 1.3% of participants. Rates differed between US and Asian studies: any ARIA was reported in 19.5% versus 9.7%, ARIA-E in 10.6% versus 2.5%, ARIA-H in 15.2% versus 7.0%, and symptomatic ARIA in 3.3% versus 0.1%. These are comparisons between study populations, not evidence that ARIA risk changed over time or that geography itself caused the differences. People with two copies of the APOE ε4 allele had the highest pooled rates of any ARIA, ARIA-E and ARIA-H, at 34.1%, 10.3% and 18.9%, respectively. The corresponding rates were 14.5%, 4.7% and 12.0% among heterozygotes and 11.0%, 2.9% and 6.7% among non-carriers. Baseline microhemorrhage was associated with any ARIA at 23.4% versus 11.5% among those without microhemorrhage and with ARIA-H at 19.3% versus 4.2%; the rates of ARIA-E were 5.4% and 5.7%, respectively. ARIA incidence did not differ significantly by baseline CDR severity or deep white matter hyperintensity burden.

Safety outcomes also included treatment discontinuations and other adverse events. In total, 12.2% of participants discontinued treatment for any reason, 6.2% because of adverse events and 3.5% because of ARIA. Infusion-related reactions occurred in 18.5% and serious adverse events in 2.8%. The analysis found statistically significant cognitive changes only for MoCA at three months or less, based on two studies, with a mean difference of 0.515 (95% confidence interval, 0.451–0.578). No statistically significant changes were observed in the other available cognitive outcomes. Because much of the real-world evidence lacked concurrent control groups, the absence of a significant change cannot establish that lecanemab has no effect, and the review did not provide controlled evidence sufficient to confirm efficacy.

Amyloid PET measurements showed reductions in the studies reporting them. At six months, the estimated mean difference on the Centiloid scale was −28.453 (95% confidence interval, −37.708 to −19.198), and at 12 months the mean difference in standardized uptake value ratio was −0.171 (95% confidence interval, −0.291 to −0.052). These biomarker changes do not by themselves demonstrate improved clinical outcomes. The authors described the work as the first large-scale systematic review and meta-analysis focused on real-world safety and clinical utility of lecanemab, and said that sensitivity analyses supported the robustness of the pooled results. They concluded that ARIA safety outcomes may be influenced by APOE ε4 genotype and baseline microbleeds, and that longer-term controlled studies across regions are needed to clarify comparative safety and whether biomarker changes translate into meaningful clinical benefits.

Subject of Research: Real-world safety and clinical evidence for lecanemab in Alzheimer’s disease

Article Title: Real-world safety and efficacy of lecanemab in the treatment of Alzheimer’s disease: a systematic review and meta-analysis

Article References: Wu, Y., Zhu, L., Chen, J., Liu, J., Yin, K., & Yang, X. (2026). Real-world safety and efficacy of lecanemab in the treatment of Alzheimer’s disease: a systematic review and meta-analysis. Journal of Neurology, 273(11), Article 675. https://doi.org/10.1007/s00415-026-14224-y

Image Credits: AI Generated

DOI: 10.1007/s00415-026-14224-y

Keywords: lecanemab, Alzheimer’s disease, ARIA, amyloid PET, APOE ε4, microhemorrhage, real-world evidence, meta-analysis, treatment safety, cognitive outcomes, Real-world, safety