Department of Neurology, Jeonbuk National University Medical School and Hospital, 20 Geonji-ro, Deokjin-gu, Jeonju, 54907, South Korea.
Research Institute of Clinical Medicine of Jeonbuk National University-Biomedical Research Institute of Jeonbuk National University Hospital, Jeonju, South Korea.
Trials. 2022 Sep 27;23(1):813. doi: 10.1186/s13063-022-06781-0.
Cholinesterase inhibitors (ChEIs) decrease long-term cognitive decline in patients with Alzheimer's disease (AD); however, there is little evidence that ChEIs affect cognitive test scores in patients with mild cognitive impairment (MCI). Conventional endpoints, such as cognitive tests or clinical rating scores, may lack the sensitivity to subtle treatment effects in participants with MCI. Therefore, there is an immediate need to refocus on direct physiological assessments to detect the effects of ChEIs in patients with MCI due to AD.
We propose a randomized controlled trial to evaluate the effect of donepezil, a ChEI, on patients with MCI due to AD. We plan to recruit 78 participants (39 in each arm) with MCI who had amyloid positron emission tomography (PET)-positive results for this open-label study. To evaluate subtle differences, we will measure eye-tracking metrics and digital pen data while participants perform the simplified Rey Complex Figure (RCFT) and clock drawing tests. The primary outcome is a change in the ratio of the number of fixations (working space/perceptual space) performed using the simplified RCFT, from baseline to 12 weeks, as assessed using eye-tracking metrics. The secondary outcomes are changes in general cognition, clinical severity, activities of daily living, and visuospatial function assessed using standard rating scores and digital pen data. The analyses of the primary and secondary outcomes will be based on the difference in changes during follow-up between the donepezil and control groups using the t-test or Mann-Whitney U test, as well as adjusting for baseline values.
This study is designed to determine whether eye-tracking metrics can detect the effect of donepezil on visuospatial dysfunction more sensitively in patients with MCI. It is expected that multimodal data, such as eye-tracking and digital pen data, may provide helpful biomarkers for identifying subtle changes that are difficult to measure using conventional methods.
Clinical Research Information Service, Republic of Korea (CRIS, cris.nih.go.kr) KCT0006236. Registered on June 10, 2021.
胆碱酯酶抑制剂（ChEIs）可减少阿尔茨海默病（AD）患者的长期认知下降；然而，几乎没有证据表明 ChEIs 会影响轻度认知障碍（MCI）患者的认知测试分数。传统的终点，如认知测试或临床评分，可能缺乏对 MCI 参与者细微治疗效果的敏感性。因此，现在迫切需要重新关注直接的生理评估，以检测 ChEIs 在 AD 引起的 MCI 患者中的作用。
我们提出了一项随机对照试验，以评估胆碱酯酶抑制剂多奈哌齐对 AD 引起的 MCI 患者的影响。我们计划招募 78 名 MCI 参与者（每组 39 名），这些参与者的淀粉样蛋白正电子发射断层扫描（PET）结果为阳性，这是一项开放标签研究。为了评估细微差异，我们将在参与者进行简化 Rey 复杂图形（RCFT）和时钟绘制测试时，测量眼动跟踪指标和数字笔数据。主要结局是使用眼动跟踪指标评估，从基线到 12 周，简化 RCFT 中注视次数（工作空间/感知空间）的比值的变化。次要结局是使用标准评分和数字笔数据评估一般认知、临床严重程度、日常生活活动和视空间功能的变化。主要和次要结局的分析将基于治疗组和对照组在随访期间的变化差异，使用 t 检验或曼-惠特尼 U 检验，并根据基线值进行调整。
这项研究旨在确定眼动跟踪指标是否可以更敏感地检测多奈哌齐对 MCI 患者视空间功能障碍的作用。预计多模态数据，如眼动跟踪和数字笔数据，可能为识别使用传统方法难以测量的细微变化提供有帮助的生物标志物。
韩国临床研究信息服务（CRIS，cris.nih.go.kr）KCT0006236。于 2021 年 6 月 10 日注册。
