眼动评价系统在早期阿尔茨海默病中的应用基础研究

Alzheimer’s disease (AD) is a major public health problem in aging society. The present control strategy for this disease is “early diagnosis, early treatment initiation, and maintaining drug therapy”. However, currently available method for AD screening and follow-up evaluation is still cognition examination, which is less sensitive for patients with early AD, while alternative methods like biomarker measurements and special neuroimaging assessments are not widely accessible and relatively expensive. Hence it is important to establish a sensitive and easy tool for AD evaluation, so as to assist early AD diagnosis and clinical development of novel anti-AD drugs. Impaired eye movement has been demonstrated in early AD patients, but evidences about underlying connections between eye movement and the disease progression of AD are currently lacking. Thus the present project is intended to investigate the disease-specific eye-movement pattern of AD patients, as well as the correlation between changes of eye movement measures and AD progression or therapeutic effects of anti-AD drugs on AD patients. The purpose is to establish a sensitive eye-movement system for the evaluation of early AD patients. Our prior studies have built up a battery of easy-operating and robust eye movement tests and validated the sensitivity of these tests for age-related performance change and the effect of midazolam at clinical dose. We plan to optimize and extend the content of current eye movement battery and apply it in a 2-year follow-up study on early AD patients and normal controls. The assessments of this study will include eye movement tests, 18F-FDG-PET examination, measurements of biomarkers in the cerebro-spinal fluid, cognitive function, and genetic polymorphism that is associated with AD prognosis. This study is expected to provide the application basis for the use of eye movement tests in early AD evaluation through neuropsychological, neuroimaging, and pathophysiological dimensions.

阿尔茨海默病(AD)是老龄化社会的重大公共卫生问题，其控制策略是“早诊早治，坚持用药”。目前通过认知检查筛选和随访AD的方法对早期AD欠敏感，生物标志物检测和特殊影像学检查尚未普及且昂贵，因此亟需找到敏感且易操作的评估工具，辅助AD的早期发现和临床新药研发。眼动涉及广泛脑部活动，与认知密切相关。早期AD患者即存在眼动异常，但目前尚缺乏眼动与AD病程进展相关性的应用基础研究。本课题拟研究早期AD 患者的眼动特征、眼动与AD病程及疗效的关系，构建对早期AD敏感的眼动评价系统。前期试验建立了简单可靠的眼动检测，并验证了方法对年龄和咪达唑仑药效的敏感性。本课题将优化和扩展现有眼动检查，对早期AD患者和对照随访2年，评估眼动、FDG-PET、脑脊液生物标志物和认知功能，并检测与AD预后相关的敏感基因，从神经心理学、神经影像学和病理生理学角度研究眼动与AD的关系，确立眼动评估早期AD的应用基础。

阿尔茨海默病(AD)是老龄化社会的重大公共卫生问题，其控制策略是“早诊早治，坚持用药”，但目前通过认知检查筛选和随访AD的方法对早期AD欠敏感，生物标志物检测和特殊影像学检查尚未普及且昂贵，因此亟需找到敏感且易操作的评估工具，辅助AD的早期发现和临床新药研发。眼动涉及广泛脑部活动，与认知密切相关。早期AD患者即存在眼动异常，但目前尚缺乏眼动与AD病程进展相关性的应用基础研究。本课题构建了对早期AD敏感的简便易行的标准化眼动检查范式，并以眼动检查指标为基础，通过收集294名健康受试者、33名阿尔茨海默病（AD）患者、16名帕金森病（PD）患者、6名其他神经系统变性病患者的数据，建立了随年龄变化的眼动检查值数学模型，确定了AD患者的眼动变化特征及其诊断界值，并与PD及其他神经变性病患者进行鉴别。通过这个模型，可以识别出不同年龄段“脑老化”超出正常范围的个体，作为筛查早期AD的有利工具。该方法的敏感性高达93%，特异性为80%。同时，本课题组还发现，老年人的眼动变化与脑电图变化对应的脑区及频谱相关，进一步说明眼动变化存在神经解剖和神经生理学基础，为眼动评估用于早期AD患者的评估奠定了重要的应用基础。受COVID-19疫情影响，本课题原计划的长期随访研究推后完成，因此有关长期随访的研究结果尚需通过数据分析确定。