Alzheimer's disease is the neurodegenerative disorder responsible for approximately 60% to 70% of all cases of dementia and is expected to affect 152 million by 2050. Recently, anti-amyloid therapies have been developed and approved by the Food and Drug Administration as disease-modifying treatments given as infusions every 2 to 5 weeks for Alzheimer's disease. Although this is an important milestone in mitigating Alzheimer's disease progression, it is critical for emergency medicine clinicians to understand what anti-amyloid therapies are and how they work to recognize, treat, and mitigate their adverse effects. Anti-amyloid therapies may be underrecognized contributors to emergency department visits because they carry the risk of adverse effects, namely amyloid-related imaging abnormalities. Amyloid-related imaging abnormalities are observed as abnormalities on magnetic resonance imaging as computed tomography is not sensitive enough to detect the microvasculature abnormalities causing vasogenic edema (amyloid-related imaging abnormalities-E) microhemorrhages and hemosiderin deposits (amyloid-related imaging abnormalities-H). Patients presenting with amyloid-related imaging abnormalities may have nonspecific neurologic symptoms, including headache, lethargy, confusion, and seizures. Anti-amyloid therapies may increase risk of hemorrhagic conversion of ischemic stroke patients receiving thrombolytics and complicate the initiation of anticoagulation. Given the novelty of anti-amyloid therapies and limited real-world data pertaining to amyloid-related imaging abnormalities, it is important for emergency medicine clinicians to be aware of these agents.
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http://dx.doi.org/10.1016/j.annemergmed.2024.12.002 | DOI Listing |
Transl Neurodegener
January 2025
Department of Biochemistry, College of Medicine, Konyang University, 158, Gwanjeodong-Ro Seo-Gu, Daejeon, 35365, Republic of Korea.
Alzheimer's disease (AD) is the most common type of dementia. Monoclonal antibodies (MABs) serve as a promising therapeutic approach for AD by selectively targeting key pathogenic factors, such as amyloid-β (Aβ) peptide, tau protein, and neuroinflammation. Specifically, based on their efficacy in removing Aβ plaques from the brains of patients with AD, the U.
View Article and Find Full Text PDFJ Neurol
January 2025
Neuroimaging Research Unit, Division of Neuroscience, IRCCS San Raffaele Scientific Institute, Milan, Italy.
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.
Diseases
January 2025
Departamento de Medicina, Facultad de Ciencias de la Salud, Universidad de Oviedo, ES-33006 Oviedo, Spain.
Background/objective: Neurotoxic soluble amyloid-β (Aβ) oligomers are key drivers of Alzheimer's pathology, with evidence suggesting that early targeting of these soluble forms may slow disease progression. Traditional intravenous (IV) monoclonal antibodies (mAbs) face challenges, including limited brain penetration and risks such as amyloid-related imaging abnormalities (ARIA). This hypothetical study aimed to model amyloid dynamics in early-to-moderate Alzheimer's disease (AD) and compare the efficacy of IV mAn with intrathecal pseudodelivery, a novel method that confines mAbs in a subcutaneous reservoir for selective amyloid clearance in cerebrospinal fluid (CSF) without systemic exposure.
View Article and Find Full Text PDFJAMA Netw Open
January 2025
Alzheimer Center Limburg, Department of Psychiatry and Neuropsychology, School for Mental Health and Neuroscience, Maastricht University, Maastricht, the Netherlands.
Importance: Baseline cerebral microbleeds (CMBs) and APOE ε4 allele copy number are important risk factors for amyloid-related imaging abnormalities in patients with Alzheimer disease (AD) receiving therapies to lower amyloid-β plaque levels.
Objective: To provide prevalence estimates of any, no more than 4, or fewer than 2 CMBs in association with amyloid status, APOE ε4 copy number, and age.
Design, Setting, And Participants: This cross-sectional study used data included in the Amyloid Biomarker Study data pooling initiative (January 1, 2012, to the present [data collection is ongoing]).
Neurology
January 2025
Neurology Unit, Department of Clinical and Experimental Sciences, University of Brescia, Italy.
Objectives: Cerebral amyloid angiopathy (CAA) is the main driver of amyloid-related imaging abnormalities (ARIAs) in Alzheimer disease (AD). We compared different versions of the Boston criteria for CAA diagnosis in AD.
Methods: This article presents a single-center analysis (outpatient neurodegenerative clinic) of patients with AD with mild cognitive impairment (MCI) or early dementia, meeting NIA-AA criteria and having biological amyloid confirmation (CSF or imaging).
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