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S5‐01‐04: Imaging Outcomes for Clinical Trials in Different Stages of Alzheimer's Disease
Author(s) -
Vernooij Meike
Publication year - 2011
Publication title -
alzheimer's and dementia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.713
H-Index - 118
eISSN - 1552-5279
pISSN - 1552-5260
DOI - 10.1016/j.jalz.2011.05.2425
Subject(s) - disease , medicine , clinical trial , neuroscience , psychology
not available. S5-01-05 VASOGENIC EDEMA IN IMMUNOTHERAPY: SIGN OF EFFICACY OR DANGER Stephen Salloway, Brown University, Providence, R.I., United States. Background: Immunotherapy trials in AD patients aimed at Ab lowering have been associated with a spectrum of reversible neuroimaging abnormalities referred to as vasogenic edema (VE). The MRI features include hyperintensities in grey and white matter and leptomeninges and sulcal effacement on FLAIR sequences, and siderosis, and cerebral microbleeds (CMBs) on gradient echo sequences. We wanted to report the imaging characteristics, risk factors, clinical course, and possible pathophysiology of the VE syndrome associated with amyloid-based treatments, and discuss the degree to which VE represents a sign of target engagement, toxicity, or both. Methods: This analysis is based on the results of two 18 month, phase 2, multiple ascending dose trials of bapineuzumab for mild-moderate AD with additional information from other reports of VE associated with amyloid-based trials. Results: VE was seen in 14 cases in the initial bapineuzumab studies. Three cases of VE have been reported in a 6 month trial of a BMS-708163gamma secretase inhibitor for mild-moderate AD (ICAD 2011) and VE was seen before treatment in 2 AD patients treated with semagacestat and solanezumab. In the bapineuzumab trials, VE ranged from subtle changes to extensive, multi-focal lesions. Most cases of VE occurred after one of the first 3 doses. Eight of 14 cases were asymptomatic and most were detected on routine studyMRI scans. Bapineuzumabwas held after detection of VE and most cases resolved on follow-up imaging. In 6 patients re-treated with bapineuzumab, VE did not recur. With bapineuzumab, VE was related to higher dose, apolipoprotein eE 4 carrier status, and the number of CMBs. All 3 subjects in the BMS-708163 gamma secretase trial were ApoE4 carriers and two were homozygous. These 3 subjects had 3, 6, and 118 baseline CMBs suggesting underlying amyloid angiopathy. The imaging findings resemble those seen in amyloid angiopathy. Early on, antiamyloid immunotherapy may induce a transfer of soluble amyloid from SYMPOSIA S5-01: Imaging Outcomes for Clinical Trials in Different Stages of Alzheimer’s Disease S806