Temporal Evolution of ARIA After Lecanemab Interruption: A Longitudinal Volumetric MRI Study

The temporal evolution of amyloid-related imaging abnormalities (ARIA) after lecanemab interruption is incompletely characterized. We quantified longitudinal ARIA-E (vasogenic edema and/or sulcal effusion) volumetric change and associated ARIA-H (cerebral microhemorrhages and/or superficial siderosis) on follow-up MRI, including assessment across APOE genotype groups.

In this retrospective study at a tertiary academic center, we identified patients who developed ARIA-E during lecanemab therapy and had longitudinal brain MRI exams for analysis. ARIA-E lesions were segmented on 3D FLAIR to obtain volumetric measurements at the first ARIA-E positive scan and at two follow-up MRIs after treatment interruption. ARIA-H (new cerebral microhemorrhages and superficial siderosis) was assessed on susceptibility-weighted/gradient-echo sequences at each time point. Patients were stratified by APOE genotype (ε4 non-carriers, ε3/ε4 heterozygotes, ε4/ε4 homozygotes).

The cohort included 24 patients (8 ε4 non-carriers, 9 ε3/ε4 heterozygotes, 7 ε4/ε4 homozygotes). The mean interval time from ARIA-E detection to the first follow-up MRI was 31.6 ± 2.4 days (95% CI, 29.6-32.6), and from the first to the second follow-up MRI was 42.9 ± 27.4 days (95% CI, 31.6-47.1). ARIA-E volume decreased by a mean of 47.5% (from 6.3 cm³ to 3.3 cm³) at the first follow-up and demonstrated an overall mean reduction of 92% (from 6.3 cm³ to 0.5 cm³) by the second follow-up over a period of 74.5 ± 27.7 days. Complete radiographic resolution of ARIA-E occurred in 18/24 (75%) patients by the second follow-up (6/8 non-carriers, 7/9 heterozygotes, 4/7 homozygotes). ARIA-H developed in 20/24 (83.3%) patients, including microhemorrhages in 17/24 and superficial siderosis in 7/24.

After lecanemab interruption, ARIA-E shows marked early reversibility, with complete radiographic resolution in the majority of cases within 2-3 months. The high frequency of ARIA-H supports continued MRI surveillance after ARIA-E detection to confirm resolution and identify hemorrhagic manifestations relevant to management.