Longitudinal multimodal MRI analysis of lecanemab treatment in mild cognitive impairment: a pilot study of
Toshiya Takahashi1, Dinh Ha Duy Thuy2, Shingo Takenaka3
1Department of Neurology, Graduate School of Medicine, Kyoto University, Kyoto, Japan.
Background:
Lecanemab, a monoclonal antibody targeting soluble amyloid-β protofibrils, has demonstrated efficacy in reducing amyloid burden in patients with mild cognitive impairment (MCI). However, its effects on brain structure, cerebral perfusion, gray matter microstructure and white matter microstructure remain unclear.
Methods:
This exploratory longitudinal study aimed to evaluate changes in brain volume, cerebral blood flow (CBF), and diffusion tensor imaging (DTI) measures over a 12-month treatment period in 8 patients with MCI receiving biweekly lecanemab infusions. MRI scans were acquired at baseline and at 6, 9, and 12 months using three-dimensional T1-weighted, pseudo-continuous arterial spin labeling (pCASL), and DTI sequences. Changes in whole-brain and regional indices were assessed using the Wilcoxon signed-rank test.
Results:
Compared to baseline, brain volume showed significant reductions at all follow-up points across all examined regions, including the whole brain, hippocampus, posterior cingulate cortex, and precuneus. CBF remained stable throughout the observation period in both global and regional analyses. Both fractional anisotropy (FA) and mean diffusivity (MD) showed significant deterioration at the whole-brain level. However, in the hippocampus, left precuneus and cingulum (cingulate gyrus), MD increased significantly at several timepoints, whereas FA remained relatively preserved, suggesting localized preservation of microstructural integrity. Neuropsychological test scores remained stable over time, with no significant deterioration observed across MMSE-J, MoCA-J, CDR-SB, or ADAS-J Cog scores. In parallel, cerebrospinal fluid biomarkers showed significant improvements in Aβ42, Aβ42/40 ratio, and p-tau181 at 6 and 12 months.
Conclusion:
These findings suggest that lecanemab may help maintain cerebral perfusion and partially preserve gray matter microstructure and white matter integrity during the early course of treatment in patients with MCI, despite concurrent volumetric and microstructural changes. Multimodal MRI may contribute to monitoring treatment response in patients with MCI receiving lecanemab.
Insights
Lecanemab treatment in mild cognitive impairment (MCI) patients showed stable cerebral blood flow and some preservation of brain microstructure, despite overall brain volume reduction. This suggests lecanemab may offer benefits in early treatment stages.
Area of Science:
- Neuroscience
- Radiology
- Pharmacology
Background:
- Lecanemab, an amyloid-beta targeting monoclonal antibody, shows promise in reducing amyloid burden in mild cognitive impairment (MCI).
- However, its impact on brain structure, cerebral perfusion, and microstructural integrity in MCI patients requires further investigation.
Purpose of the Study:
- To longitudinally evaluate the effects of lecanemab on brain volume, cerebral blood flow (CBF), and diffusion tensor imaging (DTI) measures over 12 months in MCI patients.
- To assess changes in gray matter and white matter microstructure during lecanemab treatment.
Main Methods:
- An exploratory longitudinal study involving 8 MCI patients receiving biweekly lecanemab infusions.
- Multimodal MRI (3D T1-weighted, pseudo-continuous arterial spin labeling, DTI) was performed at baseline and 6, 9, and 12 months.
- Statistical analysis used the Wilcoxon signed-rank test to assess changes in whole-brain and regional indices.
Main Results:
- Significant whole-brain volume reduction was observed, but cerebral blood flow remained stable.
- Whole-brain white matter integrity showed deterioration (increased MD, decreased FA), yet localized regions (hippocampus, precuneus, cingulum) exhibited preserved microstructural integrity.
- Neuropsychological scores and key cerebrospinal fluid biomarkers (Aβ42, Aβ42/40, p-tau181) showed stability or improvement.
Conclusions:
- Lecanemab may help maintain cerebral perfusion and partially preserve gray and white matter microstructure in early MCI treatment, despite volumetric changes.
- Multimodal MRI is a valuable tool for monitoring lecanemab treatment response in MCI patients.
