title: Amyloid-related imaging abnormalities in amyloid-modifying therapeutic trials: recommendations from the Alzheimer's Association Research Roundtable Workgroup.
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.
authors.affiliation: Center for Alzheimer Research and Treatment, Department of Neurology, Brigham and Women's Hospital, Boston, MA, USA. reisa@rics.bwh.harvard.edu
authors.forename: Reisa A
authors.initials: RA
authors.lastname: Sperling
authors.forename: Clifford R
authors.initials: CR
authors.lastname: Jack
authors.forename: Sandra E
authors.initials: SE
authors.lastname: Black
authors.forename: Matthew P
authors.initials: MP
authors.lastname: Frosch
authors.forename: Steven M
authors.initials: SM
authors.lastname: Greenberg
authors.forename: Bradley T
authors.initials: BT
authors.lastname: Hyman
authors.forename: Philip
authors.initials: P
authors.lastname: Scheltens
authors.forename: Maria C
authors.initials: MC
authors.lastname: Carrillo
authors.forename: William
authors.initials: W
authors.lastname: Thies
authors.forename: Martin M
authors.initials: MM
authors.lastname: Bednar
authors.forename: Ronald S
authors.initials: RS
authors.lastname: Black
authors.forename: H Robert
authors.initials: HR
authors.lastname: Brashear
authors.forename: Michael
authors.initials: M
authors.lastname: Grundman
authors.forename: Eric R
authors.initials: ER
authors.lastname: Siemers
authors.forename: Howard H
authors.initials: HH
authors.lastname: Feldman
authors.forename: Rachel J
authors.initials: RJ
authors.lastname: Schindler
mesh_terms: D000544:Alzheimer Disease / Q000150:complications / Q000473:pathology / Q000628:therapy; D000682:Amyloid / Q000276:immunology / Q000378:metabolism*; D000818:Animals; D001929:Brain Edema / Q000209:etiology / Q000378:metabolism / Q000473:pathology; D002543:Cerebral Hemorrhage / Q000209:etiology / Q000378:metabolism / Q000473:pathology; D002986:Clinical Trials as Topic / Q000379:methods* / Q000592:standards; D004195:Disease Models, Animal; D006801:Humans; D008279:Magnetic Resonance Imaging; D012955:Societies, Medical / Q000458:organization & administration*
chemical_list: D000682:Amyloid