Jing Qi ¹ Tenghong Lian ² Peng Guo ² Mingyue He ¹ Jinghui Li ¹ Jing Li ¹ Dongmei Luo ¹ Yanan Zhang ³ Yue Huang ^1,4 Gaifen Liu ^1,4 Zijing Zheng ¹ Huiying Guan ¹ Weijia Zhang ¹ Hao Yue ¹ Zhan Liu ¹ Fan Zhang ¹ Yao Meng ¹ Ruidan Wang ¹ Wenjing Zhang ¹ Wei Zhang ^1,2,4*

• ¹ Department of Neurology, Beijing Tiantan Hospital Capital Medical University, Beijing, China
• ² Center for Cognitive Neurology, Department of Neurology, Beijing Tiantan Hospital, 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

Background: Abnormal eye movements occur in 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 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).Patients with AD exhibit distinct patterns of abnormal eye movements. These 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.