Tokushige Shin-Ichi, Matsumoto Hideyuki, Matsuda Shun-Ichi, Inomata-Terada Satomi, Kotsuki Naoki, Hamada Masashi, Tsuji Shoji, Ugawa Yoshikazu, Terao Yasuo
Department of Neurology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.
Department of Neurology, Kyorin University, Tokyo, Japan.
Front Aging Neurosci. 2023 Mar 21;15:1123456. doi: 10.3389/fnagi.2023.1123456. eCollection 2023.
Patients with Alzheimer's disease (AD) are known to exhibit visuospatial processing impairment, as reflected in eye movements from the early stages of the disease. We investigated whether the pattern of gaze exploration during visual tasks could be useful for detecting cognitive decline at the earliest stage.
Sixteen AD patients (age: 79.1 ± 7.9 years, Mini Mental State Examination [MMSE] score: 17.7 ± 5.3, mean ± standard deviation) and 16 control subjects (age: 79.4 ± 4.6, MMSE score: 26.9 ± 2.4) participated. In the visual memory task, subjects memorized presented line drawings for later recall. In the visual search tasks, they searched for a target Landolt ring of specific orientation (serial search task) or color (pop-out task) embedded among arrays of distractors. Using video-oculography, saccade parameters, patterns of gaze exploration, and pupil size change during task performance were recorded and compared between AD and control subjects.
In the visual memory task, the number of informative regions of interest (ROIs) fixated was significantly reduced in AD patients compared to control subjects. In the visual search task, AD patients took a significantly longer time and more saccades to detect the target in the serial but not in pop-out search. In both tasks, there was no significant difference in the saccade frequency and amplitude between groups. On-task pupil modulation during the serial search task was decreased in AD. The number of ROIs fixated in the visual memory task and search time and saccade numbers in the serial search task differentiated both groups of subjects with high sensitivity, whereas saccade parameters of pupil size modulation were effective in confirming normal cognition from cognitive decline with high specificity.
Reduced fixation on informative ROIs reflected impaired attentional allocation. Increased search time and saccade numbers in the visual search task indicated inefficient visual processing. Decreased on-task pupil size during visual search suggested decreased pupil modulation with cognitive load in AD patients, reflecting impaired function of the locus coeruleus. When patients perform the combination of these tasks to visualize multiple aspects of visuospatial processing, cognitive decline can be detected at an early stage with high sensitivity and specificity and its progression be evaluated.
众所周知，阿尔茨海默病（AD）患者存在视觉空间处理障碍，从疾病早期阶段的眼球运动中即可体现出来。我们研究了视觉任务期间的注视探索模式是否有助于在最早阶段检测认知衰退。
16名AD患者（年龄：79.1±7.9岁，简易精神状态检查表[MMSE]评分：17.7±5.3，均值±标准差）和16名对照受试者（年龄：79.4±4.6，MMSE评分：26.9±2.4）参与研究。在视觉记忆任务中，受试者记住呈现的线条图以便后续回忆。在视觉搜索任务中，他们在干扰物阵列中搜索特定方向（序列搜索任务）或颜色（突现任务）的目标兰多尔特环。使用视频眼动描记法，记录AD患者和对照受试者在任务执行期间的扫视参数、注视探索模式和瞳孔大小变化，并进行比较。
在视觉记忆任务中，与对照受试者相比，AD患者注视的信息性感兴趣区域（ROI）数量显著减少。在视觉搜索任务中，AD患者在序列搜索而非突现搜索中检测目标花费的时间显著更长，扫视次数更多。在两项任务中，两组之间的扫视频率和幅度均无显著差异。AD患者在序列搜索任务期间的任务中瞳孔调节减少。视觉记忆任务中注视的ROI数量以及序列搜索任务中的搜索时间和扫视次数以高灵敏度区分了两组受试者，而扫视参数和瞳孔大小调节在以高特异性从认知衰退中确认正常认知方面有效。
对信息性ROI的注视减少反映了注意力分配受损。视觉搜索任务中搜索时间和扫视次数增加表明视觉处理效率低下。视觉搜索期间任务中瞳孔大小减小表明AD患者认知负荷下瞳孔调节减少，反映了蓝斑功能受损。当患者执行这些任务的组合以可视化视觉空间处理的多个方面时，可以以高灵敏度和特异性在早期阶段检测到认知衰退并评估其进展。
