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 2,762 associated with AD. Additional cohorts should be evaluated to 
support these findings.