Department of Neurology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
Neuroscience Center, Samsung Medical Center, Seoul, Korea.
Eur J Neurol. 2022 Apr;29(4):980-989. doi: 10.1111/ene.15241. Epub 2022 Jan 26.
Previous studies have developed several cognitive composites in preclinical Alzheimer disease (AD). However, more sensitive measures to track cognitive changes and therapeutic efficacy in preclinical AD are needed considering the diverse sociocultural and linguistic backgrounds. This study developed a composite score that can sensitively detect the amyloid-β (Aβ)-related cognitive trajectory of preclinical AD using Korean data.
A total of 196 cognitively normal participants who underwent amyloid positron emission tomography were followed-up with neuropsychological assessments. We developed the Longitudinal Amyloid Cognitive Composite in Preclinical AD (LACPA) using the linear mixed-effects model (LMM) and z scores. The LMM was also used to investigate the longitudinal sensitivity of the LACPA and the association between time-varying brain atrophy and the LACPA.
Considering the group-time interaction effects of each subtest, the Seoul Verbal Learning Test-Elderly version immediate recall/delayed recall/recognition, the Korean Trail Making Test B Time, and the Korean Mini-Mental State Examination were selected as components of the LACPA. The LACPA exhibited a significant group-time interaction effect between the Aβ+ and Aβ- groups (t = -3.288, p = 0.001). Associations between time-varying LACPA and brain atrophy were found in the bilateral medial temporal, right lateral parietal, and right lateral frontal regions, and hippocampal volume.
The LACPA may contribute to reduction in time and financial burden when monitoring Aβ-related cognitive decline and therapeutic efficacy of the disease-modifying agents specifically targeting Aβ in secondary prevention trials.
既往研究已在临床前阿尔茨海默病（AD）中开发了几种认知综合指标。然而，鉴于不同的社会文化和语言背景，需要更敏感的指标来跟踪临床前 AD 的认知变化和治疗效果。本研究使用韩国数据开发了一种综合评分，可灵敏地检测临床前 AD 的淀粉样蛋白-β（Aβ）相关认知轨迹。
共纳入 196 名认知正常、接受过正电子发射断层扫描（PET）的参与者，对其进行了神经心理学评估。我们使用线性混合效应模型（LMM）和 z 分数开发了临床前 AD 中纵向淀粉样蛋白认知综合指标（LACPA）。LMM 还用于研究 LACPA 的纵向敏感性，以及时变脑萎缩与 LACPA 的关系。
考虑到每个子测试的组-时间交互效应，选择了首尔词语学习测试-老年版即刻回忆/延迟回忆/再认、韩国连线测试 B 时间和韩国简易精神状态检查作为 LACPA 的组成部分。LACPA 在 Aβ+和 Aβ-组之间表现出显著的组-时间交互效应（t=-3.288，p=0.001）。LACPA 与脑萎缩的时变之间存在相关性，表现在双侧内侧颞叶、右侧外侧顶叶和右侧外侧额叶以及海马体积。
LACPA 可能有助于减少监测 Aβ相关认知下降和针对 Aβ 的疾病修饰药物在二级预防试验中的治疗效果的时间和经济负担。
