Investigating Multimodal Diagnostic Eye Biomarkers of Cognitive Impairment by Measuring Vascular and Neurogenic Changes in the Retina
Investigating Multimodal Diagnostic Eye Biomarkers of Cognitive Impairment by Measuring Vascular and Neurogenic Changes in the Retina
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DOI：
10.3389/fphys.2018.01721
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发表时间：
2018-12-06
影响因子：
4
通讯作者：
Santiesteban, Carlos Mendoza
中科院分区：
文献类型：
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作者：
DeBuc, Delia Cabrera;Somfai, Gabor Mark;Santiesteban, Carlos Mendoza
以往的研究表明，认知障碍(CI)不仅限于大脑，还会影响视网膜。在这项先导性研究中，我们使用一种低成本的多模式方法研究了视网膜血管复杂性与CL患者神经退行性改变之间的相关性。使用先进的视网膜成像、全场视网膜电信号(ERG)和视觉功能检查对每个受试者(n=69)的视网膜结构和功能进行了量化。用新加坡研究所血管评估软件计算视网膜血管参数。使用蒙特利尔认知评估来测量CI。变量间进行皮尔逊乘积矩相关分析。在69名参与者中，32人患有CI(46%)。我们发现与对照组(0.6+/-0.2)相比，脑梗死组(较大的静脉不对称系数：0.7+/-0.2)的微血管网络发生了显著改变。CI(容量、信息和关联维度：D-0、D-1和D-2(平均值+/-SD)：1.57+/-0.06；1.56+/-0.06；1.55+/-0.06；年龄81+/-6岁)低于对照组(1.61+/-0.03；1.59+/-0.03；1.58+/-0.03；年龄：80+/-7岁)。此外，在轻度CI患者中，周边视网膜中的葡萄膜样区以及色素弥散也被注意到。脑梗死组患者的色觉功能受损，ERG波幅较小，峰值时间较长。皮尔逊积矩相关分析显示血管参数(动静脉比、总长径比、D-0、D-1、D-2)与闪光反应的隐含时间(IT)显著相关，但这些相关性在偏相关中不显著。这项研究表明，存在可能对CI下降敏感的多模式视网膜标志物，并进一步证明了视网膜神经元功能障碍与微血管变化之间的相关性的统计趋势，表明视网膜几何血管和功能参数可能与CI引起的视网膜生理变化有关。我们怀疑，我们对结构-功能联合参数的分析，而不是单个生物标志物的分析，可能会提供一个有用的CI临床标志物，也可以为CI的鉴别诊断提供更高的敏感性和特异性。然而，由于我们的研究样本很小，我们的方法的临床适用性的全面程度是具有挑衅性的，仍然有待确定。
Previous studies have demonstrated that cognitive impairment (CI) is not limited to the brain but also affects the retina. In this pilot study, we investigated the correlation between the retinal vascular complexity and neurodegenerative changes in patients with Cl using a low-cost multimodal approach. Quantification of the retinal structure and function were conducted for every subject (n = 69) using advanced retinal imaging, full-field electroretinogram (ERG) and visual performance exams. The retinal vascular parameters were calculated using the Singapore Institute Vessel Assessment software. The Montreal Cognitive Assessment was used to measure CI. Pearson product moment correlation was performed between variables. Of the 69 participants, 32 had CI (46%). We found significantly altered microvascular network in individuals with CI (larger venular-asymmetry factor: 0.7 +/- 0.2) compared with controls (0.6 +/- 0.2). The vascular fractal dimension was lower in individuals with CI (capacity, information and correlation dimensions: D-0, D-1, and D-2 (mean +/- SD): 1.57 +/- 0.06; 1.56 +/- 0.06; 1.55 +/- 0.06; age 81 +/- 6years) vs. controls (1.61 +/- 0.03; 1.59 +/- 0.03; 1.58 +/- 0.03; age: 80 +/- 7 years). Also, drusen-like regions in the peripheral retina along with pigment dispersion were noted in subjects with mild CI. Functional loss in color vision as well as smaller ERG amplitudes and larger peak times were observed in the subjects with CI. Pearson product moment correlation showed significant associations between the vascular parameters (artery-vein ratio, total length-diameter ratio, D-0, D-1, D-2 and the implicit time (IT) of the flicker response but these associations were not significant in the partial correlations. This study illustrates that there are multimodal retinal markers that may be sensitive to CI decline, and adds to the evidence that there is a statistical trend pointing to the correlation between retinal neuronal dysfunction and microvasculature changes suggesting that retinal geometric vascular and functional parameters might be associated with physiological changes in the retina due to CI. We suspect our analysis of combined structural-functional parameters, instead of individual biomarkers, may provide a useful clinical marker of CI that could also provide increased sensitivity and specificity for the differential diagnosis of CI. However, because of our study sample was small, the full extent of clinical applicability of our approach is provocative and still to be determined.