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ASSOCIATIONS

Alzheimer’s Association (ALZ.org)

Browse Professional Information, tools, and resources for those working in the field of Alzheimer’s disease and dementia care.

ALZ.org

PUBLISHED ARTICLES

Detection and Management of Amyloid-Related Imaging Abnormalities in Patients with Alzheimer’s Disease Treated with Anti-Amyloid Beta Therapy.

  • Literature on ARIA from anti-amyloid β therapy studies about potential risk factors, detection, and management is summarized
  • ARIA may be related to binding of antibodies to accumulated Aβ in both the cerebral parenchyma and vasculature, resulting in loss of vessel wall integrity and increased leakage into surrounding tissues
  • ARIA-E is identified as vasogenic edema in the brain parenchyma or sulcal effusions in the leptomeninges/sulci
  • ARIA tends to be transient and asymptomatic, typically occurring early during treatment, with the risk decreasing later in treatment
  • Management approaches following ARIA are discussed

Barakos J. et al. J Prev Alzheimers Dis. 2022;9(2):211–220.

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Amyloid-Related Imaging Abnormalities with Emerging Alzheimer Disease Therapeutics: Detection and Reporting Recommendations for Clinical Practice.

  • Monoclonal antibodies are emerging disease-modifying therapies for Alzheimer disease that require brain MR imaging for eligibility assessment as well as for monitoring for ARIA
  • ARIA with edema or effusion are transient, treatment-induced edema or sulcal effusion, identified on T2-FLAIR
  • ARIA with hemorrhage are treatment-induced microhemorrhages or superficial siderosis identified on T2* gradient recalled-echo
  • As monoclonal antibodies become more widely available, treatment screening and monitoring brain MR imaging examinations may increase neuroradiology practice volumes
  • Radiologists must become familiar with the imaging appearance of ARIA, how to select an appropriate imaging protocol, and report findings in clinical practice
  • Based on clinical trial literature and expert experience from clinical trial imaging:
    • Imaging findings of amyloid-related imaging abnormalities are summarized
    • Potential interpretation pitfalls are described
    • Recommendations for a standardized imaging protocol and an amyloid-related imaging abnormalities reporting template are provided

Cogswell PM, et al. AJNR Am J Neuroradiol. 2022;43(9):E19–E35.

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Altered Clearance and Amyloid-Related Imaging Abnormalities.

  • The goal of this article is to provide updated practical considerations for radiologists, including implementation of MR imaging protocols, workflows, and reporting and communication practices relevant to anti-amyloid immunotherapy and monitoring for ARIA
  • On the basis of consensus discussion within an expanded American Society of Neuroradiology (ASNR) Alzheimer, ARIA, and Dementia Study Group, our purpose is the following:
    • Summarize the FDA guidelines for the evaluation of radiographic ARIA
    • Review the 3 key MRI sequences for ARIA monitoring and standardized imaging protocols on the basis of ASNR-industry collaborations
    • Provide imaging recommendations for 3 key patient scenarios
    • Highlight the role of the radiologist in the care team for this population
    • Discuss implementation of MRI protocols to detect ARIA in diverse practice settings
    • Present the results of the 2023 ASNR international neuroradiologist practice survey on dementia and ARIA imaging

Cogswell PM, et al. Neuroimaging Clin N Am. 2025;35(2):267–275.

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Alzheimer Disease Anti-Amyloid Immunotherapies: Imaging Recommendations and Practice Considerations for Monitoring of Amyloid-Related Imaging Abnormalities.

  • ARIA are parenchymal edema/effusion and hemorrhage that occur as side effects of immunotherapies targeting beta-amyloid for patients with AD
  • The mechanism of ARIA remains unclear but is thought to be due to:
    • Loss of vascular integrity secondary to overwhelming perivascular clearance pathways
    • Worsening of CAA
    • Removal of amyloid from the vessel wall
    • Initiation of a local immune response
  • Further imaging and neuropathological studies may help further inform the mechanism of ARIA and its relationship to underlying AD and CAA pathology

Cogswell PM, et al. AJNR Am J Neuroradiol. 2025;46(1):24–32.

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Amyloid-Related Imaging Abnormalities and Aβ-Amyloid-Targeting Antibodies: A Systematic Review.

  • Available evidence on ARIAs from RCTs testing anti-Aβ-amyloid mAbs in patients with AD was summarized to provide a comprehensive update about risk factors, clinical correlates, and implications for withholding and reinitiating treatment
  • Signal alterations that included parenchymal edema and sulcal effusion leading to transient hyperintensities on fluid-attenuated inversion recovery and T2-weighted sequences were termed ARIA-E, whereas those consisting of hemosiderin deposits, including parenchymal microhemorrhages and leptomeningeal superficial siderosis, were termed ARIA-H
  • ApoE ε4 genotype was the main risk factor for both ARIA types
  • ARIA-E incidence was further associated with treatment dose
  • Both ARIA types manifested early during study course
  • Symptomatic cases accounted for the 6.1% to 39.3% of ARIA-E cases at higher treatment doses across RCTs, whereas ARIA-H cases were generally asymptomatic
  • Most ARIA-E cases resolved with treatment withholding, although corticosteroid administration was required anecdotally
  • ARIA-E recurrence after dose reinitiation or adjustment varied from 13.8% to 25.6% across RCTs
  • Evidence suggests that ARIAs are frequent, mostly asymptomatic collateral events of amyloid-modifying therapies, highlighting the need for standardized clinical and neuroradiological management protocols in real-world clinical settings

Filippi M et al. JAMA Neurol. 2022;79(3):291.

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Cerebral Amyloid Angiopathy and Alzheimer Disease – One Peptide, Two Pathways.

  • The pathogenic pathways of CAA and AD intersect at the levels of Aβ generation, its circulation within the interstitial fluid and perivascular drainage pathways and its brain clearance but diverge in their mechanisms of brain injury and disease presentation
  • Evidence for and the pathogenic implications of interactions between CAA and AD is reviewed
  • Both pathologies seem to be driven by impaired Aβ clearance, creating conditions for a self-reinforcing cycle of increased vascular Aβ, reduced perivascular clearance and further CAA and AD progression
  • Despite the close relationship between vascular and plaque Aβ deposition, several factors favor one or the other, such as the carboxy-terminal site of the peptide and specific co-deposited proteins
  • Amyloid-related imaging abnormalities that have been seen in trials of anti-Aβ immunotherapy are another probable intersection between CAA and AD, representing overload of perivascular clearance pathways and the effects of removing Aβ from CAA-positive vessels

Greenberg SM, et al. Nat Rev Neurol. 2020 Jan;16(1):30–42.

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Amyloid-Related Imaging Abnormalities (ARIA): Radiological, Biological, and Clinical Characteristics.

  • This review provides a comprehensive state-of-the-art conceptual review of radiological features, clinical detection and classification challenges, pathophysiology, underlying biological mechanism(s) and risk factors/predictors associated with ARIA
  • The existing literature and current lines of evidence with ARIA-edema/effusion (ARIA-E) and ARIA-hemosiderosis/ microhemorrhages (ARIA-H) seen across anti-amyloid clinical trials and therapeutic development are summarized
  • ARIA shares many clinical, biological and pathophysiological features with AD and CAA. There is a great need to conceptually link the evident synergistic interplay associated with such underlying conditions to allow clinicians and researchers to further understand, deliberate and investigate on the combined effects of these multiple pathophysiological processes
  • Moreover, this review article aims to better assist clinicians in detection (either observed via symptoms or visually on MRI), management based on appropriate use recommendations, and general preparedness and awareness when ARIA are observed as well as researchers in the fundamental understanding of the various antibodies in development and their associated risks of ARIA
  • To facilitate ARIA detection in clinical trials and clinical practice, the implementation of standardized MRI protocols and rigorous reporting standards are recommended

Hampel H, et al. Brain. 2023;146(11):4414–4424.

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Amyloid-Beta Antibody Binding to Cerebral Amyloid Angiopathy Fibrils and Risk for Amyloid-Related Imaging Abnormalities.

  • Therapeutic antibodies have been developed to target amyloid-beta (Aβ), and some of these slow the progression of AD. However, they can also cause adverse events known as ARIA-E
  • This study investigates therapeutic Aβ antibody binding to CAA fibrils isolated from human leptomeningeal tissue to study whether this related to the ARIA-E frequencies previously reported by clinical trials
  • The binding of Aβ antibodies to CAA Aβ fibrils was evaluated in vitro using immunoprecipitation, surface plasmon resonance, and direct binding assay
  • Marked differences in Aβ antibody binding to CAA fibrils were observed
  • The findings of this study support the proposal that Aβ antibody-CAA interactions may relate to the ARIA-E frequency observed in patients treated with Aβ-based immunotherapies

Söderberg L, et al. Sci Rep. 2024;14(1):10868.

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Amyloid-Related Imaging Abnormalities in Amyloid-Modifying Therapeutic Trials: Recommendations from the Alzheimer’s Association Research Roundtable Workgroup.

  • In response to concerns raised by the Food and Drug Administration, the Alzheimer’s Association Research Roundtable convened a working group to review publicly available trial data
  • The etiology of ARIA remains unclear but the prevailing data support vascular amyloid as a common pathophysiological mechanism leading to increased vascular permeability
  • The workgroup proposes recommendations for the detection and monitoring of ARIA in ongoing AD clinical trials, as well as directions for future research

Sperling RA, et al. Alzheimers Dement. 2011;7(4):367–385.

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CONTINUING MEDICAL EDUCATION

Browse Professional Information, tools, and resources for those working in the field of Alzheimer’s disease and dementia care.

These links are provided for informational purposes and the presence of this content on UnderstandingARIA.com (“Website”) does not constitute the review, approval, or endorsement by these organizations of this website.

Alzheimer’s Association (ALZ.org)

An Introduction to Amyloid-Related Imaging Abnormalities (ARIA) and Its Management

ALZ.org

American Society for Neuroradiology (ASNR)

Alzheimer’s Webinar Series and link to directory of ARIA Educated Practitioners

ASNR.org