Favorable long-term cognitive outcomes following recurrent ARIA linked to amyloid-lowering therapies: two cases

INTRODUCTION: The large-scale approval of anti-amyloid monoclonal antibodies for treating Alzheimer's disease (AD) has raised concerns about their safety due to treatment-emergent amyloid-related imaging abnormalities (ARIA). METHODS: We present two cases of patients diagnosed with mild cognitive impairment due to AD who were enrolled in the GRADUATE I clinical trial. They received subcutaneous gantenerumab every two weeks during the study period. RESULTS: Both patients experienced recurrent ARIA-Effusion/Edema type (ARIA-E). One developed symptomatic and severe ARIA, leading to hospitalization and study withdrawal. We report a long follow-up post-randomization (65 and 54 months), during which the adverse events did not appear to have a negative impact on disease progression. Additionally, one patient had a negative amyloid-PET over a year after treatment cessation. DISCUSSION: These cases suggest that recurrent ARIA-E do not inevitably lead to accelerated progression, instead, may relate to possible long-term benefits. The mechanisms underlying these findings warrant further real-life evidence.