Evaluation of the effects of lecanemab treatment on brain atrophy using voxel-based specific regional analysis system for Alzheimer's disease

Abstract

Background

Lecanemab, a monoclonal antibody targeting amyloid-β (Aβ), has been shown to reduce Aβ plaques and slow cognitive decline in patients with Alzheimer's disease (AD). However, its effect on brain structure in real-world clinical settings remains unclear. The voxel-based specific regional analysis system for Alzheimer's disease (VSRAD) enables quantitative assessment of brain atrophy, particularly in the medial temporal lobe, using MRI.

Objective

To evaluate the effects of lecanemab on brain structure by analyzing changes in Z-scores derived from VSRAD in AD patients treated with lecanemab in actual clinical practice.

Methods

This retrospective study included 16 patients with AD who received four biweekly administrations of lecanemab (10 mg/kg) between February 2023 and August 2024. Amyloid pathology was confirmed via ¹⁸F-flutemetamol PET and cerebrospinal fluid Aβ_42/40 ratio. VSRAD analysis was performed using three-dimensional sagittal T1-weighted MRI scans obtained before the first and after the fourth lecanemab administration. Changes in the Z-score of medial temporal lobe (MTL) and MTL/whole brain ratios were assessed.

Results

After four doses of lecanemab, the Z-score of MTL in AD patients significantly decreased from 1.61 ± 0.76 to 1.38 ± 0.67 (p < 0.01), and the MTL/whole brain ratio significantly decreased from 6.47 ± 6.48 to 4.59 ± 4.80 (p < 0.02).

Conclusions

Lecanemab treatment was associated with a significant reduction in the Z-score of MTL, indicating a decrease in brain volume. The clinical significance of this brain volumetric change remains uncertain, and hence longitudinal studies linking brain volume reduction with clinical outcomes, including cognition, are warranted.