Imaging of Amyloid-Related Imaging Abnormalities (ARIA)

Abstract

Patients with Alzheimer’s disease (AD) can now be treated with monoclonal antibodies aiming at clearing amyloid plaques from the brain parenchyma. Weeks after initiation of this drug therapy, patients may develop so-called amyloid-related imaging abnormalities (ARIA) on MRI. ARIA comprise vasogenic edema and leptomeningeal effusions (ARIA-E) as well as microbleeds and superficial hemosiderosis (ARIA-H). The prevalence is drug- and dose-dependent (up to 40 % of patients), the apolipoprotein E4 variant and concomitant cerebral amyloid angiopathy (CAA) increase the risk. With regard to MRI characteristics, ARIA strongly resembles the so-called inflammatory subtype of CAA (CAA-ri). While patients with CAA-ri are typically detected due to symptoms such as headaches, lethargy, confusion, and rarely epileptic seizures, around 20 % of ARIA patients show symptoms. Management of ARIA is not yet clearly established. In asymptomatic patients, discontinuation of the drug might be sufficient.

Key points 

• Amyloid-related imaging abnormalities (ARIA) occur in around 20 % of patients who are treated with monoclonal antibodies against amyloid β.

• There are 2 types: ARIA-E (edema effusion) und ARIA-H (hemorrhage).

• Depending on the severity, therapy with monoclonal antibodies is either interrupted or finished.

Citation Format

• Urbach H, Linn J, Hattingen E et al. Imaging of Amyloid-Related Imaging Abnormalities (ARIA). Fortschr Röntgenstr 2024; 196: 363 – 369

Keywords

MR-imaging - Alzheimer disease - dementia

Publikationsverlauf

Eingereicht: 29. Mai 2023

Angenommen: 02. September 2023

Artikel online veröffentlicht:
23. November 2023

• References

• 1 S3-Leitlinie „Demenzen“. https://www.awmf.org/uploads/tx_szleitlinien/038-013l_S3-Demenzen-2016-07.pdf
• 2 Hejl A, Høgh P, Waldemar G. Potentially reversible conditions in 1000 consecutive memory clinic patients. J Neurol Neurosurg Psychiatry 2002; 73: 390-394
• 3 Klöppel S, Yang S, Kellner E. et al. Voxel-wise deviations from healthy aging for the detection of region-specific atrophy. Neuroimage Clin 2018; 20: 851-860
• 4 Urbach H, Egger K. MRT bei neurodegenerativen Erkrankungen. Fortschritte der Neurologie Psychiatrie 2020; 88: 266-284
• 5 Nedergaard M. Garbage Truck of the Brain. Science 2013; 340: 1529-1530
• 6 van Dyck CH, Swanson CJ, Aisen P. et al. Lecanemab in Early Alzheimer’s Disease. NEJM 2022;
• 7 https://investor.lilly.com/news-releases/news-release-details/lillys-donanemab-significantly-slowed-cognitive-and-functional Pressemitteilung 3.5.23
• 8 Jansen WJ, Ossenkoppele R, Knol DL. et al. Prevalence of cerebral amyloid pathology in persons without dementia: a meta-analysis. JAMA 2015; 313: 1924-1938
• 9 Sakai K, Ueda M, Fukushima W. et al. Nationwide survey of cerebral amyloid angiopathy in Japan. Eur J Neurol 2019; 26: 1487-1493
• 10 https://www.nice.org.uk/guidance/conditions-and-diseases/mental-health-and-behavioural-conditions/dementia
• 11 Attems J, Lauda F, Jellinger KA. Unexpectedly low prevalence of intracerebral hemorrhages in sporadic cerebral amyloid angiopathy. An autopsy study. Journal of Neurology 2008; 255: 70-76
• 12 Attems J, Jellinger KA, Thal DR. et al. Review: Sporadic cerebral amyloid angiopathy. Neuropathology and Applied Neurobiology 2011; 37: 75-93
• 13 van Veluw SJ, Scherlek AA, Freeze WM. et al. Different microvascular alterations underlie microbleeds and microinfarcts. Ann Neurol 2019; 86: 279-292
• 14 Greenberg SM, Charidimou A. Diagnosis of Cerebral Amyloid Angiopathy: Evolution of the Boston Criteria. Stroke 2018; 49: 491-497
• 15 Charidimou A, Shakeshaft C, Werring DJ. Cerebral microbleeds on magnetic resonance imaging and anticoagulant-associated intracerebral hemorrhage risk. Front Neurol 2012; 3: 133
• 16 Jakel L, De Kort AM, Klijn CJM. et al. Prevalence of cerebral amyloid angiopathy: A systematic review and meta-analysis. Alzheimers Dement 2022; 18: 10-28
• 17 Linn J, Halpin A, Demaerel P. et al. Prevalence of superficial siderosis in patients with cerebral amyloid angiopathy. Neurology 2010; 74: 1346-1350
• 18 Charidimou A, Boulouis G, Frosch MP. et al. The Boston criteria version 2.0 for cerebral amyloid angiopathy: a multicentre, retrospective, MRI-neuropathology diagnostic accuracy study. Lancet Neurol 2022; 21: 714-725
• 19 Auriel E, Charidimou A, Gurol ME. et al. Validation of Clinicoradiological Criteria for the Diagnosis of Cerebral Amyloid Angiopathy-Related Inflammation. JAMA Neurol 2016; 73: 197-202
• 20 Schaumberg J, Trauscheid M, Eckert B. et al. [Cerebral amyloid angiopathy associated with inflammation]. Nervenarzt 2018; 89: 682-691
• 21 Scolding NJ, Joseph F, Kirby PA. et al. Aβ-related angiitis: primary angiitis of the central nervous system associated with cerebral amyloid angiopathy. Brain 2005; 128: 500-515
• 22 Greenberg SM, Bacskai BJ, Hernandez-Guillamon M. et al. Cerebral amyloid angiopathy and Alzheimer disease – one peptide, two pathways. Nat Rev Neurol 2020; 16: 30-42
• 23 Kinnecom C, Lev MH, Wendell L. et al. Course of cerebral amyloid angiopathy-related inflammation. Neurology 2007; 68: 1411-1416
• 24 Reinhard M, Lorenz L, Sommerlade L. et al. Impaired dynamic cerebral autoregulation in patients with cerebral amyloid angiopathy. Brain Res 2019; 1717: 60-65
• 25 Sevigny J, Chiao P, Bussière T. et al. The antibody aducanumab reduces Aβ plaques in Alzheimer’s disease. Nature 2016; 537: 50-56
• 26 Sevigny J, Chiao P, Bussière T. et al. Addendum: The antibody aducanumab reduces Aβ plaques in Alzheimer’s disease. Nature 2017; 546: 564
• 27 Aisen PS, Cummings J, Doody R. et al. The future of Anti-Amyloid trials. J Prev Alzheimers Dis 2020; 7: 146-151
• 28 Cummings J, Lee G, Ritter A. et al. Alzheimer’s disease drug development pipeline: 2020. Alzheimers Dement (NY) 2020; 6: e12050
• 29 Cummings J. Anti-Amyloid Monoclonal Antibodies are Transformative Treatments that Redefine Alzheimer’s Disease Therapeutics. Drugs 2023;
• 30 Roytman M, Mashriqi F, Al-Tawil K. et al. Amyloid-Related Imaging Abnormalities: An Update. Am J Roentgenol 2023; 220: 562-574
• 31 Sperling RA, Jack Jr CR, Black SE. et al. Amyloid-related imaging abnormalities in amyloid-modifying therapeutic trials: recommendations from the Alzheimer’s Association Research Roundtable Workgroup. Alzheimer Dement 2011; 7: 367-385
• 32 Barakos J, Sperling R, Salloway S. et al. MR Imaging Features of Amyloid-Related Imaging Abnormalities. AJNR Am J Neuroradiol 2013; 34: 1958-1965
• 33 Barkhof F, Daams M, Scheltens P. et al. An MRI rating scale for amyloid-related imaging abnormalities with edema or effusion. AJNR Am J Neuroradiol 2013; 34: 1550-1555
• 34 Klein G, Scelsi MA, Barakos J. et al. Comparing ARIA-E severity scales and effects of treatment management thresholds. Alzheimers Dement (Amst) 2022; 14 (01) e12376
• 35 Salloway S, Chalkias S, Barkhof F. et al. Amyloid-Related Imaging Abnormalities in 2 Phase 3 Studies Evaluating Aducanumab in Patients With Early Alzheimer Disease. JAMA Neurol 2022; 79: 13-21
• 36 Filippi M, Cecchetti G, Spinelli EG. et al. Amyloid-Related Imaging Abnormalities and β-Amyloid-Targeting Antibodies: A Systematic Review. JAMA Neurol 2022; 79: 291-304
• 37 VandeVrede L, Gibbs DM, Koestler M. et al. Symptomatic amyloid-related imaging abnormalities in an APOE ε4/ε4 patient treated with aducanumab. Alzheimer’s Dement 2020; 12: e12101
• 38 Reish NJ, Jamshidi P, Stamm B. et al. Multiple Cerebral Hemorrhages in a Patient Receiving Lecanemab and Treated with t-PA for Stroke. N Engl J Med 2002; 388: 478-479