The effect of cholinesterase inhibitors on neurodegeneration in individuals with amnestic mild cognitive impairment
Gihwan Byeon 1, Min Soo Byun 2, 3, Dahyun Yi 4, Hyejin Ahn 4, 5, Gijung Jung 4, Bo Kyung Sohn 6, Joon Hyung Jung 7, Yoon Young Chang 6, Kyungtae Kim 2, Hyeji Choi 2, Yoon Hee Kim 2, Yu Kyeong Kim 8, Koung Mi Kang 9, Chul-Ho Sohn 9, Dong Young Lee 2, 3, 4*
1Department of Psychiatry, Seoul St.Mary’s Hospital, 2Department of Neuropsychiatry, Seoul National University Hospital, 3Department of Psychiatry, Seoul National University College of Medicine, 4Institute of Human Behavioral Medicine, Medical Research Center Seoul National University, 5Interdisciplinary program of cognitive science, Seoul National University College of Humanities, 6Department of Psychiatry, Sanggye Paik Hospital, College of Medicine, Inje University, 7Department of Neuropsychiatry, Chungbuk National University Hospital, 8Department of Nuclear Medicine, SMG‑SNU Boramae Medical Center, 9Department of Radiology, Seoul National University Hospital
Received: August 21, 2024; Revised: December 31, 2024; Accepted: December 31, 2024; Published online: December 31, 2024.
© The Korean College of Neuropsychopharmacology. All rights reserved.

Abstract
Objective: Cholinesterase inhibitors (ChEIs) are effective in treating mild to moderate Alzheimer’s disease (AD) dementia by compensating for acetylcholine deficiency. While their use in mild cognitive impairment (MCI) lacks strong trial support, some studies suggest they may delay neurodegeneration. This study aims to investigate ChEIs' neuroprotective effects in individuals with amnestic MCI (aMCI) using multi-modal neuroimaging, and to determine if amyloid-beta (Aβ) deposition influences these effects.
Methods: Longitudinal data from a cohort study were retrospectively analyzed. A total of 118 aMCI patients (ages 55-90), who underwent baseline evaluations encompassing the assessment of ChEI use and [11C] Pittsburgh compound B-positron emission tomography (PET), were included in the analyses. All participants also received baseline and 2-year follow-up magnetic resonance imaging (MRI) and [18F] fluorodeoxyglucose-PET imaging .
Results: The ChEI use group exhibited a significantly lesser decline in AD-signature region cerebral
metabolism (AD-CM) over a 2-year period than the ChEI non-use group (B = 0.089, 95% CI: 0.030―0.149). However, there was no significant difference in the 2-year change of AD-signature region cortical thickness (AD-CT) (B = 0.032, 95% CI: -0.075―0.138) and hippocampal volume (B = -88.013, 95% CI: -323.900―147.874) between the ChEI use and non-use groups. The presence of Aβ
pathology did not moderate the effect of ChEI use on AD-CM, AD-CT, or hippocampal volume.
Conclusions: The findings suggest that ChEIs may delay functional neurodegeneration in aMCI individuals, irrespective of the presence of amyloid pathology
Keywords: Alzheimer, Biomarkers, Cholinesterase inhibitors, Neuroimaging

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