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Prevalence of asymptomatic vasogenic edema in pretreatment Alzheimer's disease study cohorts from phase 3 trials of semagacestat and solanezumab.
MedLine Citation:
PMID:  21784350     Owner:  NLM     Status:  In-Data-Review    
Abstract/OtherAbstract:
BACKGROUND: Cerebral vasogenic edema (VE) has been reported to occur during antiamyloid immunotherapy. VE may be associated with central nervous system pathology with blood-brain barrier disruptions; however, less is known about the prevalence of naturally occurring VE in patients with Alzheimer's disease (AD).
METHODS: Fluid-attenuated inversion recovery imaging sequences were obtained from four ongoing multicenter, randomized, double-blind, placebo-controlled, phase 3 trials in patients with mild-to-moderate AD. The first set of baseline scans was from patients in volumetric magnetic resonance imaging addenda in the Interrupting Alzheimer's Dementia by EvaluatiNg Treatment of Amyloid PaThologY (IDENTITY) studies examining semagacestat, a γ-secretase inhibitor (cohort 1, n = 621). The second set of baseline scans was from the EXPanding alzhEimer's Disease InvestigaTIONs (EXPEDITION) studies examining solanezumab, an anti-Aβ monoclonal antibody (cohort 2, n = 2141). Readers were blinded to patient-identifying information and future treatment. A third set of baseline scans was from the first 700 patients who underwent protocol-specified magnetic resonance imaging before randomization in the EXPEDITION studies (cohort 3). The analysis used three neuroradiologists: two performed independent primary interpretations and the third was the adjudicator. Readers were blinded to patient information, treatment, protocol, and time point.
RESULTS: Four cases of asymptomatic VE were detected at baseline/screening. Two VE cases were due to underlying extra-axial mass lesions. The third VE case was associated with numerous microhemorrhages in keeping with cerebral amyloid angiopathy-related inflammation or Aβ-related angiitis. The final VE case demonstrated localized sulcal fluid-attenuated inversion recovery imaging hyperintensity. No VE was detected in cohort 3 by readers blinded to patient baseline status.
CONCLUSIONS: VE seems to be rare at baseline in patients with AD in clinical trials, 2 of 2762 associated with AD. Additional cohorts should be evaluated to support these findings.
Authors:
Christopher Carlson; Wahiba Estergard; Joonmi Oh; Joyce Suhy; Clifford R Jack; Eric Siemers; Jerome Barakos
Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  Alzheimer's & dementia : the journal of the Alzheimer's Association     Volume:  7     ISSN:  1552-5279     ISO Abbreviation:  Alzheimers Dement     Publication Date:  2011 Jul 
Date Detail:
Created Date:  2011-07-25     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  101231978     Medline TA:  Alzheimers Dement     Country:  United States    
Other Details:
Languages:  eng     Pagination:  396-401     Citation Subset:  IM    
Copyright Information:
Copyright © 2011 The Alzheimer's Association. Published by Elsevier Inc. All rights reserved.
Affiliation:
Eli Lilly and Company, Indianapolis, IN, USA.
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