Longitudinal multimodal MRI analysis of lecanemab treatment in mild cognitive impairment: a pilot study of structural, perfusion, and microstructural changes

TOSHIYA TAKAHASHI¹Thuy Ha Duy Dinh²Shingo Takenaka³Sayaka Ono³Maya Fukui³Yasushi Okada⁴Ｔomohiko Asada⁵Kan Niimi⁶Kaku Kimura⁶Akio Ikeda⁷Ryosuke Takahashi¹Riki Matsumoto¹Hidenao Fukuyama^1*

• ¹Department of Neurology, Graduate School of Medicine, Kyoto University, Kyoto, Japan
• ²Human Brain Research Center, Kyoto University Graduate School of Medicine, Kyoto, Japan
• ³Department of Radiology, Yasu City Hospital, Shiga, Japan
• ⁴Department of Rehabilitation, Yasu City Hospital, Shiga, Japan
• ⁵Department of Neurology, Shiga Psychiatric Medical Center, Shiga, Japan
• ⁶Department of Neurology, Yasu City Hospital, Shiga, Japan
• ⁷Department of Epilepsy, Movement Disorders and Physiology, Kyoto University Graduate School of Medicine, Kyoto, Japan

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.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. 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.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.