Amyloid-related imaging abnormalities in amyloid-modifying therapeutic trials: Recommendations from the Alzheimer's Association Research Roundtable Workgroup

Reisa A. Sperling, Clifford R. Jack, Sandra E. Black, Matthew P. Frosch, Steven M. Greenberg, Bradley T. Hyman, Philip Scheltens, Maria C. Carrillo, William Thies, Martin M. Bednar, Ronald S. Black, H. Robert Brashear, Michael Grundman, Eric R. Siemers, Howard H. Feldman, Rachel J. Schindler

Research output: Contribution to journalArticle

286 Scopus citations

Abstract

Amyloid imaging related abnormalities (ARIA) have now been reported in clinical trials with multiple therapeutic avenues to lower amyloid-β burden in Alzheimer's disease (AD). In response to concerns raised by the Food and Drug Administration, the Alzheimer's Association Research Roundtable convened a working group to review the publicly available trial data, attempts at developing animal models, and the literature on the natural history and pathology of related conditions. The spectrum of ARIA includes signal hyperintensities on fluid attenuation inversion recoverysequences thought to represent "vasogenic edema" and/or sulcal effusion (ARIA-E), as well as signal hypointensities on GRE/T2 thought to represent hemosiderin deposits (ARIA-H), including microhemorrhage and superficial siderosis. 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.

Original languageEnglish (US)
Pages (from-to)367-385
Number of pages19
JournalAlzheimer's and Dementia
Volume7
Issue number4
DOIs
StatePublished - Jul 2011

Keywords

  • Amyloid
  • MRI
  • Microhemorrhage
  • Therapeutic trials
  • Vasogenic edema

ASJC Scopus subject areas

  • Epidemiology
  • Health Policy
  • Developmental Neuroscience
  • Clinical Neurology
  • Geriatrics and Gerontology
  • Psychiatry and Mental health
  • Cellular and Molecular Neuroscience

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    Sperling, R. A., Jack, C. R., Black, S. E., Frosch, M. P., Greenberg, S. M., Hyman, B. T., Scheltens, P., Carrillo, M. C., Thies, W., Bednar, M. M., Black, R. S., Brashear, H. R., Grundman, M., Siemers, E. R., Feldman, H. H., & Schindler, R. J. (2011). Amyloid-related imaging abnormalities in amyloid-modifying therapeutic trials: Recommendations from the Alzheimer's Association Research Roundtable Workgroup. Alzheimer's and Dementia, 7(4), 367-385. https://doi.org/10.1016/j.jalz.2011.05.2351