Effects of Lecanemab on Cerebral Blood Flow and Brain Microstructure in MCI Patients
Poster No:
167
Submission Type:
Abstract Submission
Authors:
Toshiya Takahashi1, Thuy Dinh2, Kan Niimi3, Kaku Kimura3, Hidenao Fukuyama2
Institutions:
1Kyoto University Graduate School of Medicine Department of Neurology, Kyoto, Kyoto, 2Kyoto University Graduate School of Medicine Human Brain Research Center, Kyoto, Kyoto, 3Yasu City Hospital Kyoto University Graduate School of Medicine Department of Neurology, Yasu, Shiga
First Author:
Co-Author(s):
Kan Niimi
Yasu City Hospital Kyoto University Graduate School of Medicine Department of Neurology
Yasu, Shiga
Yasu City Hospital Kyoto University Graduate School of Medicine Department of Neurology
Yasu, Shiga
Kaku Kimura
Yasu City Hospital Kyoto University Graduate School of Medicine Department of Neurology
Yasu, Shiga
Yasu City Hospital Kyoto University Graduate School of Medicine Department of Neurology
Yasu, Shiga
Hidenao Fukuyama
Kyoto University Graduate School of Medicine Human Brain Research Center
Kyoto, Kyoto
Kyoto University Graduate School of Medicine Human Brain Research Center
Kyoto, Kyoto
Introduction:
Mild cognitive impairment (MCI) is a prodromal stage of Alzheimer's disease (AD), where timely intervention can delay dementia onset. Lecanemab, an anti-amyloid beta monoclonal antibody, may reduce amyloid accumulation and slow cognitive decline. This study evaluates lecanemab's effects in MCI by integrating arterial spin labeling (ASL), diffusion tensor imaging (DTI), neuropsychological assessments, and cerebrospinal fluid (CSF) biomarkers. Using advanced tract analysis (XTRACT), we combine structural, functional, and molecular measures to clarify lecanemab's mechanisms and support personalized therapeutic strategies for MCI.
Methods:
Eight MCI patients (2 males, 6 females; age 60–79) were enrolled at Yasu City Hospital. Inclusion criteria: MMSE-J 22–28, MoCA-J 18–25, CDR 0.5–1, GDS ≤8. Amyloid positivity was confirmed by CSF biomarkers (Aβ42/40 ≤0.67, p-tau181 ≥59.0 pg/mL). ADAS-J Cog was administered.
All participants received lecanemab and were evaluated after 6 months. MRI included pseudo-continuous arterial spin labeling (pcASL) for CBF and diffusion tensor imaging (DTI) for white matter integrity. Imaging analysis was performed with the FMRIB Software Library (FSL), employing BASIL for ASL and XTRACT for DTI. Threshold-Free Cluster Enhancement (TFCE) identified significant CBF changes, with family-wise error (FWE) correction applied for multiple comparisons.
All participants received lecanemab and were evaluated after 6 months. MRI included pseudo-continuous arterial spin labeling (pcASL) for CBF and diffusion tensor imaging (DTI) for white matter integrity. Imaging analysis was performed with the FMRIB Software Library (FSL), employing BASIL for ASL and XTRACT for DTI. Threshold-Free Cluster Enhancement (TFCE) identified significant CBF changes, with family-wise error (FWE) correction applied for multiple comparisons.
Results:
At 6 months, three measures showed significant changes compared to baseline: CDR-SB worsened (2.69 to 3.12; p=0.0412), while Aβ42/40 ratio (0.04 to 0.06; p=0.0163) and p-tau181 (91.64 to 83.49; p=0.0364) improved. Although changes in MMSE, MoCA, CDR-GS, ADAS-J, and Aβ42 were not significant, their small directional shifts suggest that, no pronounced deterioration occurred in MCI patients over 6 months.
Arterial spin labeling (ASL) showed significant increased CBF in the left Cingulate Gyrus anterior division, left Inferior Frontal Gyrus pars opercularis, left Insular Cortex, left Caudate, left Accumbens, left Temporal Fusiform Cortex posterior division, and bilateral Temporal Pole.
XTRACT analysis demonstrated mean improvements in FA and MD across several tracts, including the peri-genual cingulum (cbp_r), temporal cingulum (cbt_l), inferior fronto-occipital fasciculus (ifo_r), and vertical occipital fasciculus (vof_l).
No cases of amyloid-related imaging abnormalities (ARIA) were observed in the study cohort, consistent with previous findings from clinical trials of lecanemab.
Arterial spin labeling (ASL) showed significant increased CBF in the left Cingulate Gyrus anterior division, left Inferior Frontal Gyrus pars opercularis, left Insular Cortex, left Caudate, left Accumbens, left Temporal Fusiform Cortex posterior division, and bilateral Temporal Pole.
XTRACT analysis demonstrated mean improvements in FA and MD across several tracts, including the peri-genual cingulum (cbp_r), temporal cingulum (cbt_l), inferior fronto-occipital fasciculus (ifo_r), and vertical occipital fasciculus (vof_l).
No cases of amyloid-related imaging abnormalities (ARIA) were observed in the study cohort, consistent with previous findings from clinical trials of lecanemab.
·ASL-based CBF changes before and after 6 months of lecanemab treatment in MCI patients.
Conclusions:
At 6 months, lecanemab treatment in MCI patients was associated with modest but statistically significant improvements in key CSF biomarkers (Aβ42/40 ratio and p-tau181) and region-specific increases in CBF. Despite CDR-SB showed significant worsening, no clear overall cognitive decline was observed. Notably, CBF, which generally tends to decrease over time, showed increases in certain brain regions. Furthermore, although not statistically significant, there were trends toward improvement in white matter integrity (FA, MD) in some tracts. These preliminary findings are based on a small sample size, highlighting the need for further investigation with larger cohorts to confirm and extend our understanding of lecanemab's potential benefits in MCI.
Disorders of the Nervous System:
Neurodegenerative/ Late Life (eg. Parkinson’s, Alzheimer’s) 1
Modeling and Analysis Methods:
Diffusion MRI Modeling and Analysis
Task-Independent and Resting-State Analysis 2
Keywords:
Aging
Cerebral Blood Flow
Cerebro Spinal Fluid (CSF)
Cognition
Degenerative Disease
Memory
Tractography
Treatment
WHITE MATTER IMAGING - DTI, HARDI, DSI, ETC
1|2Indicates the priority used for review
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Nir, T. M., Jahanshad, N., Villalon-Reina, J. E., Toga, A. W., Jack, C. R., Weiner, M. W., Thompson, P. M., & The Alzheimer’s Disease Neuroimaging Initiative (ADNI). (2013). Effectiveness of regional DTI measures in distinguishing Alzheimer’s disease, MCI, and normal aging. NeuroImage: Clinical, 3, 180–195. https://doi.org/10.1016/j.nicl.2013.07.006