Magnetic resonance imaging measures of brain volumes across the EXPEDITION trials in mild and moderate Alzheimer's disease dementia

• Published in: Alzheimer's & dementia : translational research & clinical interventions Vol. 8; no. 1; pp. e12313 - n/a
• Main Authors: Svaldi, Diana Otero, Higgins, Ixavier A., Holdridge, Karen C., Yaari, Roy, Case, Michael, Bracoud, Luc, Scott, David, Shcherbinin, Sergey, Sims, John R.
• Format: Journal Article
• Language: English
• Published: United States John Wiley & Sons, Inc 2022; John Wiley and Sons Inc; Wiley
• Subjects: Alzheimer's disease; amyloid; Analysis of covariance; Apolipoproteins; Atrophy; Biomarkers; Cerebrospinal fluid; Dementia; Magnetic resonance imaging; Short Report; solanezumab; volumetric magnetic resonance imaging; atrophy; solanezumab; magnetic resonance imaging; amyloid; volumetric magnetic resonance imaging; Alzheimer's disease
• ISSN: 2352-8737; 2352-8737
• DOI: 10.1002/trc2.12313

Introduction Solanezumab is a monoclonal antibody that preferentially binds soluble amyloid beta and promotes its clearance from the brain. The aim of this post hoc analysis was to assess the effect of low‐dose solanezumab (400 mg) on global brain volume measures in patients with mild or moderate Alzheimer's disease (AD) dementia quantified using volumetric magnetic resonance imaging (vMRI) data from the EXPEDITION clinical trial program. Methods Patients with mild or moderate AD (EXPEDITION and EXPEDITION2) and mild AD (EXPEDITION3), were treated with either placebo or solanezumab (400 mg) every 4 weeks (Q4W) for 76 weeks. vMRI scans were acquired at baseline and at 80 weeks from 427 MRI facilities using a standardized imaging protocol. Whole brain volume (WBV) and ventricle volume (VV) changes were estimated at 80 weeks using either boundary shift integral (EXPEDITION and EXPEDITION2) or tensor‐based morphometry (EXPEDITION3). Results The pooled cohort used for this study consisted of participants with vMRI at baseline and week 80 across the three trials. Analyzed patient subgroups comprised full patient cohort (N = 2933), apolipoprotein E (APOE) ε4+ carriers (N = 1835), and patients with mild (N = 2497) or moderate AD dementia (N = 428). No significant effect (all P‐values ≥.05) of treatment was observed in the pooled sample, individual trials, or subgroups of patients with mild or moderate AD or APOE ε4 carriers, in either WBV or VV change. Discussion Analysis of patients with mild or moderate AD dementia from baseline to 80 weeks using vMRI measures of WBV and VV changes suggested that low‐dose solanezumab was not linked to changes in volumes at 80 weeks. Analysis of the pooled cohort did not demonstrate an effect on brain volumes with treatment. Evaluation of a higher dose of solanezumab in the preclinical stage of AD is currently being undertaken.