【Abstract】
Background and Objective: 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.
Methods: Patients with MCI (n=23) or AD (n=17) and age-matched cognitively normal controls (NC; n=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.
Results: 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. Hierarchicalregression analysis further demonstrated thatm-RNFL thickness, as well as hippocampal volumes, significantly associated with ADAS-cog scores.
Conclusion: 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.
【中文摘要】
背景與目的：有證據說明阿爾茨海默病（AD）會影響患者和相關動物模型的視覺。我們這項研究的目的是調查AD和輕度認知障礙（MCI）的患者，其主要視覺通路中的視覺異常及其與海馬萎縮的關係。這項研究的目的是探索在AD進展過程中眼科檢查作為生物標誌物的潛在價值。
方法：本研究納入MCI（n=23）或AD（n=17），及年齡匹配的認知正常對照（NC; n=19）。對所有參與者進行了圖案視覺誘發電位（PVEP），閃光視網膜電圖（FERG）記錄，光學相干斷層掃描（OCT）等眼科檢查，通過3T磁共振成像測定海馬體積，通過認知功能通過迷你精神狀態檢查（MMSE），蒙特婁認知評估（MoCA）和阿爾茨海默氏病評估量表-認知子量表（ADAS-cog）進行認知評估，利用皮爾遜相關性分析眼部異常與海馬體積之間的潛在關係。在調整了年齡，性別，教育和APOE4狀態等混雜因素後，進行了分層回歸模型，以確定認知表現與視覺異常以及海馬體積之間的關係。
結果：AD患者與MCI和正常人相比，PVEP中的P100波形振幅顯著降低。在FERG測試中，MCI組的視杆系統反應，杆錐系統反應和3.0Hz閃爍時間的潛伏期有所延遲，表明視杆和視錐系統在AD進展中出現異常。OCT測試顯示，MCI和AD患者的黃斑部視網膜神經纖維層（m-RNFL）厚度減少。在調整了年齡，性別和教育等混雜因素後，P100振幅仍與海馬體積顯著相關。分層回歸分析進一步表明，m-RNFL厚度以及海馬體積與ADAS-cog評分顯著相關。
結論：P100振幅和m-RNFL厚度與海馬體積呈顯著相關性，因此有可能是探究AD病理的潛在生物標記物。