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

IF 4.6 2区医学 Q1 CLINICAL NEUROLOGY Journal of Neurology Pub Date : 2025-01-24 DOI:10.1007/s00415-025-12910-x

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

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Abstract

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.

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与降低淀粉样蛋白治疗相关的复发性ARIA后良好的长期认知预后：2例。

导论：抗淀粉样蛋白单克隆抗体大规模批准用于治疗阿尔茨海默病（AD），由于治疗中出现的淀粉样蛋白相关成像异常（ARIA），引起了对其安全性的担忧。方法：我们报告了两例被诊断为AD引起的轻度认知障碍的患者，他们参加了GRADUATE I临床试验。在研究期间，他们每两周接受一次皮下注射。结果：两例患者均出现复发性aria -积液/水肿型（ARIA-E）。1例出现症状性严重ARIA，导致住院和退出研究。我们报告了随机化后的长期随访（65和54个月），在此期间，不良事件似乎没有对疾病进展产生负面影响。此外，一名患者在停止治疗一年后淀粉样蛋白pet呈阴性。讨论：这些病例表明，复发性ARIA-E并不必然导致加速进展，相反，可能与可能的长期益处有关。这些发现背后的机制需要进一步的现实证据。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Journal of Neurology 医学-临床神经学

CiteScore

10.00

自引率

5.00%

发文量

558

审稿时长

1 months

期刊介绍： The Journal of Neurology is an international peer-reviewed journal which provides a source for publishing original communications and reviews on clinical neurology covering the whole field. In addition, Letters to the Editors serve as a forum for clinical cases and the exchange of ideas which highlight important new findings. A section on Neurological progress serves to summarise the major findings in certain fields of neurology. Commentaries on new developments in clinical neuroscience, which may be commissioned or submitted, are published as editorials. Every neurologist interested in the current diagnosis and treatment of neurological disorders needs access to the information contained in this valuable journal.