| Neuroimaging  

Alzheimer’s Disease and Amyloid-related imaging abnormalities

This Neurology Update is focused on Amyloid-Related Imaging Abnormalities (ARIA). ARIA refers to a group of brain imaging abnormalities that may be observed in Alzheimer's Disease subjects treated with anti-amyloid treatment. Neurology and neuroradiology practitioners should be aware of this emerging clinical entity and the recommendations for its management.

Amyloid-related imaging abnormalities (ARIA) are MRI abnormalities that may be identified in Alzheimer's Disease (AD) subjects treated with monoclonal antibodies targeting amyloid plaques. With the Food and Drugs Administration (FDA) approval of lecanemab and donanemab, the United States are the first country to allow the clinical use of anti-amyloid treatments to subjects with AD.
Clinical trials of these drugs showed that brain MRI abnormalities may be observed in subjects treated with these antibodies. Such abnormalities may remain clinically silent or manifest as neurological symptoms.1
The two most common type of brain MRI abnormalities are ARIA-E (edema, effusion, exudate) and ARIA-H (haemorrhage, including microhaemorrhages, and superficial siderosis). These manifestations are usually asymptomatic, as shown in clinical trials surveillance. When symptomatic, ARIA-E symptoms are usually nonlocalising (e.g. headache or confusion) but can manifest as visual disturbances, visuospatial impairment, or dys/apraxia, given the predilection for posterior brain involvement. ARIA-H is more often asymptomatic. Therefore, brain MRI surveillance is warranted in subjects on anti-amyloid treatment. Interruption or discontinuation of the drug, as well the use of steroid or antihypertensive treatments, is a clinical decision based on extension of the lesion and associated neurological manifestations. Participants enrolled on anti-amyloid clinical trials usually received scans every three months.2
The American Society of Neuroradiology recommended a minimal scanning protocol for ARIA, including T2-FLAIR, T2* GRE, and DWI sequences.2 It also recommended the use of standardized and quantitative reporting as indicated in their reporting template available in the references.3,4

Key Points:  

  1. Monoclonal antibodies targeting brain amyloid have been approved in the United States for the treatment of Alzheimer’s Disease
  2. Treatment with anti-amyloid antibodies requires brain MRI surveillance for the possible manifestation of edema (ARIA-E) and microhaemorrhages (ARIA-H)
  3. Recommendations for scanning and reporting of brain imaging abnormalities associated with anti-amyloid treatments (ARIA) were formulated.

References:

  1. Cogswell PM, Barakos JA, Barkhof F, Benzinger TS, Jack CR Jr, Poussaint TY, Raji CA, Ramanan VK, Whitlow CT. Amyloid-Related Imaging Abnormalities with Emerging Alzheimer Disease Therapeutics: Detection and Reporting Recommendations for Clinical Practice. AJNR Am J Neuroradiol. 2022 Sep;43(9):E19-E35. doi: 10.3174/ajnr.A7586. Epub 2022 Aug 11. PMID: 35953274; PMCID: PMC9451628.
  2. Cogswell PM, Andrews TJ, Barakos JA, Barkhof F, Bash S, Benayoun MD, Chiang GC, Franceschi AM, Jack CR Jr, Pillai JJ, Poussaint TY, Raji CA, Ramanan VK, Tanabe J, Tanenbaum L, Whitlow CT, Yu FF, Zaharchuk G, Zeinah M, Benzinger TS; ASNR Alzheimer’s, ARIA, and Dementia Study Group. Alzheimer's Disease Anti-Amyloid Immunotherapies: Imaging Recommendations and Practice Considerations for ARIA Monitoring. AJNR Am J Neuroradiol. 2024 Aug 23:ajnr.A8469. doi: 10.3174/ajnr.A8469. Epub ahead of print. PMID: 39179297.
  3. https://www.asnr.org/education-resources/alzheimers-webinar-series/
  4. https://www.asnr.org/wp-content/uploads/2023/07/AJNR_ARIA_white_paper_templates_20230713.pdf

Co-authors:

- Prof. Rolad Wiest, University of Bern
- Prof. Maria A. Rocca, UniSR Università Vita-Salute San Raffaele
- Prof. Meike Vernooij, Erasmus MC University Medical Center, Rotterdam

Publish on behalf of the Scientific Panel on Neuroimaging

Back