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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.
  • Limited data are available on continued dosing following radiographic findings of ARIA; Treatment should be continued with caution and regular monitoring.
    • Management approaches such as temporary suspension of treatment until symptoms or radiographic signs of ARIA have resolved or permanent discontinuation of treatment are discussed.
    • ARIA largely resolves without concomitant treatment, and there are no systematic data on potential treatments for ARIA.
    • The simple magnetic resonance imaging sequences used in clinical trials are likely sufficient for effective detection of cases.
PIPN-3086​
Barakos J. et al. J Prev Alzheimers Dis. 2022;9(2):211-220.

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
PIPN-3086​
Cogswell PM, et al. AJNR Am J Neuroradiol. 2022;43(9):E19-E35.

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.
PIPN-3086
Sperling RA, et al. Alzheimers Dement. 2011;7(4):367-385.

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

  • Available evidence on ARIAs from RCTs testing anti-β-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.
PIPN-3086​
Filippi M et al. JAMA Neurol. 2022;79(3):291.

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.
PIPN-3086
Greenberg SM et al. Nat Rev Neurol. 2020 Jan;16(1):30-42.

Continuing Medical Education

Alzheimer’s Association (ALZ.org)

An Introduction to Amyloid-Related Imaging Abnormalities (ARIA) and Its Management (75-minute continuous webinar)

Link

American Society for Neuroradiology (ASNR)

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

Link

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