Key Points Question What are the characteristics of amyloid-related imaging abnormalities (ARIA) during aducanumab treatment in individuals with early Alzheimer disease? Findings In an integrated safety data set of 2 phase 3 clinical trials (EMERGE and ENGAGE) including 3285 participants, 425 patients (41.3%) in the combined 10 mg/kg aducanumab group (n = 1029) experienced ARIA; ARIA-edema occurred in 362 patients (35.2%), and 94 of these patients (26.0%) experienced associated symptoms (eg, headache, confusion, dizziness, and nausea). ARIA-microhemorrhage and ARIA–superficial siderosis occurred in 197 patients (19.1%) and 151 patients (14.7%), respectively. Meaning Amyloid-related imaging abnormalities occurred in approximately 40% of participants in the phase 3 studies of aducanumab, and approximately one-quarter of these patients experienced symptoms.

Routine measurement of the cochlear height and bony island of the lateral semicircular canal, in conjunction with visual inspection of CT images, will increase recognition of common inner ear malformations.

Amyloid positron emission tomography (PET) imaging is being investigated as a screening tool to identify amyloid-positive patients as an enrichment strategy for Alzheimer disease (AD) clinical trial enrollment. In a multicenter, phase 1b trial, patients meeting clinical criteria for prodromal or mild AD underwent florbetapir PET scanning at screening. PET, magnetic resonance imaging, and coregistered PET/magnetic resonance imaging scans were reviewed by 2 independent readers and binary visual readings tabulated. Semiquantitative values of cortical to whole cerebellar standard uptake value ratios were computed (threshold 1.10). Of 278 patients with an evaluable PET scan, 170 (61%) and 185 (67%) were amyloid-positive by visual reading and quantitative analysis, respectively; 39% were excluded from the study due to an amyloid-negative scan based on visual readings. More ApoE ε4 carriers than noncarriers were amyloid-positive (80% vs. 43%). Comparison of visual readings with quantitative results identified 21 discordant cases (92% agreement). Interreader and intrareader agreements from visual readings were 98% and 100%, respectively. Amyloid PET imaging is an effective and feasible screening tool for enrollment of amyloid-positive patients with early stages of AD into clinical trials.