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

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• 作者：Reisa A. Sperling^a ; ^b ; ^{reisa@rics.bwh.harvard.edu"" rel=""nofollow} ; Clifford R. Jack Jr.^c ; Sandra E. Black^d ; Matthew P. Frosch^e ; Steven M. Greenberg^f ; Bradley T. Hyman^g ; Philip Scheltens^h ; Maria C. Carrilloⁱ ; William Thiesⁱ ; Martin M. Bednar^j ; Ronald S. Black^k ; H. Robert Brashear^l ; Michael Grundman^m ; Eric R. Siemersⁿ ; Howard H. Feldman^o ; ^p ; Rachel J. Schindler^q
• 关键词：MRI ; Amyloid ; Therapeutic trials ; Vasogenic edema ; Microhemorrhage
• 刊名：Alzheimer's Dementia
• 出版年：2011
• 出版时间：July 2011
• 年：2011
• 卷：7
• 期：4
• 页码：367-385
• 全文大小：1309 K

文摘

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.