Department of Neuropsychiatry, Kangwon National University Hospital, Chuncheon, Korea.
Department of Neuropsychiatry, Seoul National University Hospital, Seoul, Korea.
J Alzheimers Dis. 2024;101(1):91-97. doi: 10.3233/JAD-240380.
Clinical trial findings on cholinesterase inhibitors (ChEIs) for mild cognitive impairment (MCI) are inconclusive, offering limited support for their MCI treatment. Given that nearly half of amnestic MCI cases lack cerebral amyloid-β (Aβ) deposition, a hallmark of Alzheimer's disease; this Aβ heterogeneity may explain inconsistent results.
This study aimed to assess whether Aβ deposition moderates ChEI effects on amnestic MCI cognition.
We examined 118 individuals with amnestic MCI (ages 55-90) in a longitudinal cohort study. Baseline and 2-year follow-up assessments included clinical evaluations, neuropsychological testing, and multimodal neuroimaging. Generalized linear models were primarily analyzed to test amyloid positivity's moderation of ChEI effects on cognitive change over 2 years. Cognitive outcomes included Mini-Mental Status Examination score, the total score of the Consortium to Establish a Registry for Alzheimer's Disease neuropsychological battery, and Clinical Dementia Rating-sum of boxes.
The analysis found no significant ChEI use x amyloid positivity interaction for all cognitive outcomes. ChEI use, irrespective of Aβ status, was associated with more cognitive decline over the 2-year period.
Aβ pathology does not appear to moderate ChEI effects on cognitive decline in MCI.
胆碱酯酶抑制剂（ChEIs）治疗轻度认知障碍（MCI）的临床试验结果尚无定论，对其治疗 MCI 的作用提供的支持十分有限。鉴于近一半遗忘型 MCI 病例缺乏阿尔茨海默病的标志性标志物——脑淀粉样蛋白-β（Aβ）沉积，这种 Aβ 的异质性可能解释了不一致的结果。
本研究旨在评估 Aβ 沉积是否调节 ChEI 对遗忘型 MCI 认知的影响。
我们在一项纵向队列研究中检查了 118 名遗忘型 MCI 患者（年龄 55-90 岁）。基线和 2 年随访评估包括临床评估、神经心理学测试和多模态神经影像学。主要采用广义线性模型来检验 Aβ 阳性对 ChEI 治疗 2 年后认知变化的调节作用。认知结局包括简易精神状态检查评分、阿尔茨海默病神经心理评估联盟成套测验的总分和临床痴呆评定量表-框总数。
分析发现，对于所有认知结局，ChEI 使用与 Aβ 阳性之间均无显著的交互作用。无论 Aβ 状态如何，ChEI 使用与 2 年内认知衰退的增加有关。
Aβ 病理似乎不能调节 ChEI 对 MCI 认知衰退的作用。
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