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Introduction <p>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).</p> Methods <p>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.</p> Results <p>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&#xa0;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.</p> Discussion <p>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.</p>

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

  • 期刊论文

  • 发表日期：

    2025年1月24日

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  • Matteo Zavarella,
  • Giordano Cecchetti,
  • Giulia Rugarli,
  • Alma Ghirelli,
  • Ilaria Bottale,
  • Francesca Orlandi,
  • Edoardo G. Spinelli,
  • Roberto Santangelo,
  • Francesca Caso,
  • Sonia Francesca Calloni,
  • Paolo Quintiliano Vezzulli,
  • Andrea Falini,
  • Giuseppe Magnani,
  • Federica Agosta,
  • Massimo Filippi

摘要

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.