INTRODUCTION: This study examines whether cholinesterase inhibitors (ChEIs) influence the progression to Alzheimer's disease (AD) dementia and cognitive trajectories in amnestic mild cognitive impairment (MCI) patients, considering their amyloid beta (A beta) status. METHODS: Kaplan-Meier and time-varying Cox models evaluated ChEI use and different A beta status on MCI-to-AD progression. Linear mixed-effects models assessed cognitive trajectories. Locally estimated scatterplot smoothing regression analyzed cognitive changes before and after ChEI initiation. RESULTS: Among 558 amnestic MCI participants (168 ChEI users), ChEI users exhibited higher risk of progression to AD dementia (hazard ratio = 1.77, 95% confidence interval: 1.15 to 2.73, p = 0.001). Both ChEI use and A beta burden independently accelerated MCI progression and cognitive decline. Cognitive trajectories demonstrated decline before ChEI initiation and continued to decline after treatment began. DISCUSSION: The association between ChEI treatment and accelerated progression to AD dementia and cognitive decline, independent of A beta status, emphasized the need to reconsider optimal timing for ChEI initiation in MCI. Highlights center dot ChEI use in MCI was associated with increased risk of progression to AD dementia. center dot ChEI use in MCI was associated with accelerated longitudinal cognitive decline. center dot Cognitive decline persisted after ChEI initiation rather than reversing. center dot ChEI effects on MCI progression to AD dementia were independent of A beta status.
基金：
Key Project of the National Natural Science
Foundation of China, Grant/Award Number:
U20A20354; Chinese Institutes forMedical
Research, Grant/Award Number: CX23YZ15;
Key Project of the National Natural Science
Foundation of China, Grant/Award Number:81530036; BeijingMunicipal Natural Science
Foundation, Grant/Award Number: 7244355;
National Key Scientific Instrument and
Equipment Development Project,
Grant/Award Number: 31627803;
STI2030-Major Projects, Grant/Award
Number: No.2021ZD0201802; Beijing Brain
Initiative from BeijingMunicipal Science &
Technology Commission, Grant/Award
Numbers: Z201100005520016,
Z201100005520017; National Natural
Science Foundation of China, Grant/Award
Number: 82401404
第一作者机构：[1]Capital Med Univ, Xuanwu Hosp, Innovat Ctr Neurol Disorders, Beijing, Peoples R China[2]Capital Med Univ, Xuanwu Hosp, Natl Clin Res Ctr Geriatr Dis, Dept Neurol, Changchun St 45, Beijing 100053, Peoples R China
共同第一作者：
通讯作者：
通讯机构：[1]Capital Med Univ, Xuanwu Hosp, Innovat Ctr Neurol Disorders, Beijing, Peoples R China[2]Capital Med Univ, Xuanwu Hosp, Natl Clin Res Ctr Geriatr Dis, Dept Neurol, Changchun St 45, Beijing 100053, Peoples R China[3]Beijing Key Lab Geriatr Cognit Disorders, Beijing, Peoples R China[4]Capital Med Univ, Clin Ctr Neurodegenerat Dis & Memory Impairment, Beijing, Peoples R China[5]Capital Med Univ, Ctr Alzheimers Dis, Beijing Inst Brain Disorders, Collaborat Innovat Ctr Brain Disorders, Beijing, Peoples R China[6]Minist Educ, Key Lab Neurodegenerat Dis, Beijing, Peoples R China[*1]Capital Med Univ, Xuanwu Hosp, Innovat Ctr Neurol Disorders, Natl Clin Res Ctr Geriatr Dis,Neurol, Changchun St 45, Beijing 100053, Peoples R China
推荐引用方式(GB/T 7714)：
Liu Wenying,Li Yan,Qin Wei,et al.The impact of cholinesterase inhibitors on cognitive trajectories in mild cognitive impairment patients based on amyloid beta status[J].ALZHEIMERS & DEMENTIA.2025,21(5):doi:10.1002/alz.70193.
APA：
Liu, Wenying,Li, Yan,Qin, Wei,Wang, Xuechu,Li, Wenwen...&Jia, Jianping.(2025).The impact of cholinesterase inhibitors on cognitive trajectories in mild cognitive impairment patients based on amyloid beta status.ALZHEIMERS & DEMENTIA,21,(5)
MLA：
Liu, Wenying,et al."The impact of cholinesterase inhibitors on cognitive trajectories in mild cognitive impairment patients based on amyloid beta status".ALZHEIMERS & DEMENTIA 21..5(2025)
医学