Abnormal eye movements: relationship with clinical symptoms and predictive value for Alzheimer's disease

Jing Qi; Tenghong Lian; Peng Guo; Mingyue He; Jinghui Li; Jing Li; Dongmei Luo; Yanan Zhang; Yue Huang; Gaifen Liu; Zijing Zheng; Huiying Guan; Weijia Zhang; Hao Yue; Zhan Liu; Fan Zhang; Yao Meng; Ruidan Wang; Wenjing Zhang; Wei Zhang

doi:10.3389/fnagi.2024.1471698

Abnormal eye movements: relationship with clinical symptoms and predictive value for Alzheimer's disease

Front Aging Neurosci. 2024 Nov 21:16:1471698. doi: 10.3389/fnagi.2024.1471698. eCollection 2024.

Authors

Jing Qi¹, Tenghong Lian², Peng Guo², Mingyue He¹, Jinghui Li¹, Jing Li¹, Dongmei Luo¹, Yanan Zhang³, Yue Huang^{1

4}, Gaifen Liu^{1

4}, Zijing Zheng¹, Huiying Guan¹, Weijia Zhang¹, Hao Yue¹, Zhan Liu¹, Fan Zhang¹, Yao Meng¹, Ruidan Wang¹, Wenjing Zhang¹, Wei Zhang^{1

2

4}

Affiliations

¹ Department of Neurology, Beijing Tiantan Hospital, Capital Medical University, Beijing, China.
² Center for Cognitive Neurology, Department of Neurology, Beijing Tiantan Hospital, Capital Medical University, Beijing, China.
³ Department of Blood Transfusion, Beijing Tiantan Hospital, Capital Medical University, Beijing, China.
⁴ China National Clinical Research Center for Neurological Diseases, Beijing Tiantan Hospital, Capital Medical University, Beijing, China.

Abstract

Background: Abnormal eye movements occur at the early stages of Alzheimer's disease (AD). However, the characteristics of abnormal eye movements of patients with AD and their relationship with clinical symptoms remain inconsistent, and their predictive value for diagnosing and monitoring the progression of AD remains unclear.

Methods: A total of 42 normal controls, 63 patients with mild cognitive impairment due to AD (AD-MCI), and 49 patients with dementia due to AD (AD-D) were recruited. Eye movements were assessed using the EyeKnow eye-tracking and analysis system. Cognitive function, neuropsychiatric symptoms, and activities of daily living were evaluated using various rating scales, and correlation analyses and receiver operating characteristic curves were performed.

Results: Patients with AD exhibited increased number of offsets and offset degrees, prolonged offset duration, and decreased accuracy in lateral fixation; reduced accuracy, prolonged saccadic duration, and decreased velocity in prosaccade; decreased accuracy and corrected rate, prolonged corrected antisaccadic duration, and reduced velocity in antisaccade; and reduced accuracy and increased inhibition failures in memory saccade. Eye movement parameters were correlated with global cognition and the cognitive domains of memory, language, attention, visuospatial ability, execution function, and activities of daily living. Subgroup analysis indicated that the associations between eye movements and clinical symptoms in patients with AD were influenced by disease severity and history of diabetes. In the AD-D and AD with diabetes groups, these associations diminished. Nevertheless, the associations persisted in the AD-MCI and AD without diabetes groups. The areas under the curves for predicting AD, AD-MCI, and AD-D were 0.835, 0.737, and 0.899, respectively (all p < 0.05).

Conclusion: Patients with AD exhibit distinct patterns of abnormal eye movements. Abnormal eye movements are significantly correlated with global cognition, multiple cognitive domains, and activities of daily living. Abnormal eye movements have a considerable predictive value for the diagnosis and progression of AD.

Keywords: Alzheimer’s disease; clinical symptoms; eye movements; lateral fixation; predictive value; saccade.

Grants and funding

The author(s) declare that financial support was received for the research, authorship, and/or publication of this article. This study was supported by the Capital’s Funds for Health Improvement and Research (CFH) (2022-2-2048), the Collaborative Research Project of Traditional Chinese and Western Medicine of the Major Difficult Disease-Alzheimer’s Disease of Beijing (2023BJSZDYNJBXTGG-018), the National Key Research and Development Program of China (2016YFC1306300, 2016YFC1306000), the Key Technology R&D Program of Beijing Municipal Education Commission (kz201610025030), the Natural Science Foundation of Beijing, China (7082032), the Project of Scientific and Technological Development of Traditional Chinese Medicine in Beijing (JJ2018-48), the Capital Clinical Characteristic Application Research (Z121107001012161), the High Level Technical Personnel Training Project of Beijing Health System, China (2009-3-26), the Project of Beijing Institute for Brain Disorders (BIBD-PXM2013_014226_07_000084).