Zhao Aonan, Fang Fang, Li Binyin, Chen Yan, Qiu Yinghui, Wu Yanli, Xu Wei, Deng Yulei
Department of Neurology, Institute of Neurology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Department of Geriatrics, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Front Aging Neurosci. 2021 Jan 22;12:597491. doi: 10.3389/fnagi.2020.597491. eCollection 2020.
Alzheimer's disease (AD) has been shown to affect vision in human patients and animal models. This study was conducted to explore ocular abnormalities in the primary visual pathway and their relationship with hippocampal atrophy in patients with AD and mild cognitive impairment (MCI). The aim of this study was to investigate the potential value of ocular examinations as a biomarker during the AD progression. Patients with MCI ( = 23) or AD ( = 17) and age-matched cognitively normal controls (NC; = 19) were enrolled. Pattern visual-evoked potentials (PVEP), flash electroretinogram (FERG) recordings and optical coherence tomography (OCT) were performed for all participants. Hippocampal volumes were measured by 3T magnetic resonance imaging. Cognitive function was assessed by Mini Mental State Examination (MMSE), Montreal Cognitive Assessment (MoCA) and Alzheimer's Disease Assessment Scale-cognitive subscale (ADAS-cog). Pearson correlation was employed to analyze the potential associations between ocular abnormalities and hippocampal volumes. Hierarchical regression models were conducted to determine associations between cognitive performances and ocular abnormalities as well as hippocampal volumes after adjusting for confounding factors including age, sex, cognitive reserve, and APOE4 status. PVEP amplitude of P100 waveform was significantly decreased in AD patients compared to MCI and normal individuals. In FERG test, delayed latencies of rod response, rod cone response and 3.0 flicker time were found in cognitively impaired groups, indicating dysfunctions of both the rod and cone systems in the disease progression. OCT test revealed reduced macular retinal nerve fiber layer (m-RNFL) thickness in MCI and AD patients, which significantly correlated with brain structure of hippocampus particularly vulnerable during the progression of AD. Interestingly, P100 amplitude showed a significant association with hippocampal volumes even after adjusting confounding factors including age, sex, and cognitive reserve. Hierarchical regression analysis further demonstrated that m-RNFL thickness, as well as hippocampal volumes, significantly associated with ADAS-cog scores. P100 amplitude and m-RNFL thickness showed significant correlations with brain structure involved in AD-related neurodegeneration, and therefore proved to be potential indicators of brain imaging pathologies.
阿尔茨海默病（AD）已被证明会影响人类患者和动物模型的视力。本研究旨在探讨AD和轻度认知障碍（MCI）患者初级视觉通路中的眼部异常及其与海马萎缩的关系。本研究的目的是调查眼部检查作为AD进展过程中生物标志物的潜在价值。纳入了MCI患者（n = 23）或AD患者（n = 17）以及年龄匹配的认知正常对照（NC；n = 19）。对所有参与者进行了图形视觉诱发电位（PVEP）、闪光视网膜电图（FERG）记录和光学相干断层扫描（OCT）。通过3T磁共振成像测量海马体积。通过简易精神状态检查（MMSE）、蒙特利尔认知评估（MoCA）和阿尔茨海默病评估量表 - 认知分量表（ADAS - cog）评估认知功能。采用Pearson相关性分析眼部异常与海马体积之间的潜在关联。进行分层回归模型以确定在调整包括年龄、性别、认知储备和APOE4状态等混杂因素后，认知表现与眼部异常以及海马体积之间的关联。与MCI患者和正常个体相比，AD患者P100波形 的PVEP振幅显著降低。在FERG测试中，在认知受损组中发现视杆细胞反应、视杆 - 视锥细胞反应和3.0闪烁时间的潜伏期延迟，表明在疾病进展过程中视杆和视锥系统均存在功能障碍。OCT测试显示MCI和AD患者的黄斑视网膜神经纤维层（m - RNFL）厚度降低，这与AD进展过程中特别易损的海马脑结构显著相关。有趣的是，即使在调整了包括年龄、性别和认知储备等混杂因素后，P100振幅仍与海马体积显示出显著关联。分层回归分析进一步表明，m - RNFL厚度以及海马体积与ADAS - cog评分显著相关。P100振幅和m - RNFL厚度与AD相关神经退行性变所涉及的脑结构显示出显著相关性，因此被证明是脑成像病理学的潜在指标。
