Abstract
INTRODUCTION: With the approval of lecanemab for treating Alzheimer's disease (AD), there is an urgent need to evaluate its safety and treatment effects on biomarkers in real-world practice. METHODS: Patients receiving lecanemab (n = 72) underwent routine 3T and 7T magnetic resonance imaging (MRI) for amyloid-related imaging abnormality (ARIA) monitoring. Longitudinal changes of iron deposition assessed by quantitative susceptibility mapping (QSM) and its association with plasma biomarkers were further evaluated. RESULTS: With use of 7T MRI, we identified characteristic perivascular features and detected ARIA with hemorrhages/hemosiderin deposition (ARIA-H) ≈4 months earlier than with 3T. QSM detected post-treatment regional susceptibility reductions. Decreased susceptibility in the temporal, frontal lobes, and the thalamus was associated with plasma amyloid beta 42 (Aβ42) and tau phosphorylated at threonine 217 (p-tau217) changes. DISCUSSION: 7T MRI provides superior ARIA-H detection and iron dynamics monitoring, supporting its role in risk stratification and therapy assessment for lecanemab-treated patients. Iron deposition measured by QSM may serve as a promising neuroimaging marker for amyloid-targeting treatments. HIGHLIGHTS: Using 7T magnetic resonance imaging (MRI), this study for the first time visualized amyloid-related imaging abnormality with hemorrhages/hemosiderin deposition (ARIA-H) at a submillimeter resolution, characterized by aggregated, clustered cerebral microbleeds in a perivascular distribution, suggesting overlapping pathology with cerebral amyloid angiopathy. The susceptibility-weighted imaging sequence on 7T MRI enabled detection of ARIA-H up to 4 months earlier. Plasma amyloid beta 42 (Aβ42) and tau phosphorylated at threonine 217 (p-tau 217) levels are sensitive biomarkers for amyloid targeted therapy. Quantitative susceptibility mapping (QSM) analysis demonstrated reduced cortical iron burden post-treatment, which has significant associations with plasma Aβ42 and p-tau 217 levels, highlighting QSM-derived iron quantification as a promising neuroimaging indicator for amyloid-targeted therapeutics.