Abstract Details

Aducanumab was approved for the treatment of mild cognitive impairment due to Alzheimer’s disease or mild dementia due to Alzheimer’s disease by the US Food and Drug Administration under the accelerated approval pathway. ICARE AD-US is a prospective, single-arm, multicenter, real-world observational study to evaluate the safety and efficacy of aducanumab across ~200 centers in the US. 

ARIA are a spectrum of imaging findings detected on brain MRI and associated with the use of amyloid beta–targeting monoclonal antibodies, including aducanumab, in patients with AD. Consistency in MRI acquisition is important for accurate assessments, efficient treatment, and reduction of variability in real-world evidence.

We describe a core standardized magnetic resonance imaging (MRI) protocol to be implemented in the International Collaboration for Real-World Evidence in Alzheimer’s Disease (ICARE AD)-US study sites for monitoring amyloid-related imaging abnormalities (ARIA) and evaluating disease progression. 

MRI will be performed per standard of care and in compliance with the US prescribing information at baseline, prior to 7th and 12th infusions, and every 6 to 12 months thereafter for up to 5 years. The protocol includes 4 sequences: 3-dimensional (3-D) T2-weighted fluid-attenuated inversion recovery (FLAIR), 2-dimensional (2-D) T2*-weighted gradient-recalled echo (GRE), diffusion-weighted imaging (DWI), and 3-D T1-weighted anatomic imaging (optional). The 3-D FLAIR and 2-D T2* GRE sequences assess and monitor brain edema or sulcal effusion (ARIA-E) and hemosiderin deposits resulting from hemorrhage in the brain parenchyma or on the pial surface (ARIA-H), respectively. DWI is recommended for differential diagnosis, and 3-D T1-weighted imaging is recommended to facilitate post processing and assessment of disease progression. 

The standardized brain MRI protocol will be described.

This protocol represents a clinically feasible approach to standardizing the ongoing assessment of ARIA and AD-related changes in patients treated with aducanumab in the real world.