MR imaging features of amyloid-related imaging abnormalities

AJNR Am J Neuroradiol. 2013 Oct;34(10):1958-65. doi: 10.3174/ajnr.A3500. Epub 2013 Apr 11.

Abstract

Background and purpose: AD is one of the few leading causes of death without a disease-modifying drug; however, hopeful agents are in various phases of development. MR imaging abnormalities, collectively referred to as amyloid-related imaging abnormalities, have been reported for several agents that target cerebral Aβ burden. ARIA includes ARIA-E, parenchymal or sulcal hyperintensities on FLAIR indicative of parenchymal edema or sulcal effusions, and ARIA-H, hypointense regions on gradient recalled-echo/T2* indicative of hemosiderin deposition. This report describes imaging characteristics of ARIA-E and ARIA-H identified during studies of bapineuzumab, a humanized monoclonal antibody against Aβ.

Materials and methods: Two neuroradiologists with knowledge of imaging changes reflective of ARIA reviewed MR imaging scans from 210 bapineuzumab-treated patients derived from 3 phase 2 studies. Each central reader interpreted the studies independently, and discrepancies were resolved by consensus. The inter-reader κ was 0.76, with 94% agreement between neuroradiologists regarding the presence or absence of ARIA-E in individual patients.

Results: Thirty-six patients were identified with incident ARIA-E (17.1%, 36/210) and 26 with incident ARIA-H (12.4%, 26/210); of those with incident ARIA-H, 24 had incident microhemorrhages and 2 had incident large superficial hemosiderin deposits.

Conclusions: In 49% of cases of ARIA-E, there was the associated appearance of ARIA-H. In treated patients without ARIA-E, the risk for incident blood products was 4%. This association between ARIA-E and ARIA-H may suggest a common pathophysiologic mechanism. Familiarity with ARIA should permit radiologists and clinicians to recognize and communicate ARIA findings more reliably for optimal patient management.

Publication types

  • Meta-Analysis
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alzheimer Disease / drug therapy*
  • Alzheimer Disease / epidemiology
  • Alzheimer Disease / pathology*
  • Amyloid beta-Peptides / metabolism
  • Amyloidosis / chemically induced*
  • Amyloidosis / epidemiology
  • Amyloidosis / pathology*
  • Antibodies, Monoclonal, Humanized / administration & dosage
  • Antibodies, Monoclonal, Humanized / adverse effects*
  • Brain / metabolism
  • Brain / pathology
  • Brain Edema / epidemiology
  • Brain Edema / pathology
  • Cerebral Hemorrhage / epidemiology
  • Cerebral Hemorrhage / pathology
  • Clinical Trials, Phase II as Topic
  • Gadolinium
  • Hemosiderin / metabolism
  • Humans
  • Incidence
  • Magnetic Resonance Imaging*
  • Randomized Controlled Trials as Topic
  • Risk Factors
  • Severity of Illness Index

Substances

  • Amyloid beta-Peptides
  • Antibodies, Monoclonal, Humanized
  • Hemosiderin
  • Gadolinium
  • bapineuzumab