Purpose To evaluate the potential of retinal optical coherence tomography (OCT) measurements and polygenic risk scores (PRS) to identify people at risk of cognitive impairment. Methods Using OCT images from 50 342 UK Biobank participants, we examined associations between retinal layer thickness and genetic risk for neurodegenerative disease and combined these metrics with PRS to predict baseline cognitive function and future cognitive deterioration. Multivariate Cox proportional hazard models were used to predict cognitive performance. P values for retinal thickness analyses are false-discovery-rate-adjusted. Results Higher Alzheimer’s disease PRS was associated with a thicker inner nuclear layer (INL), chorio-scleral interface (CSI) and inner plexiform layer (IPL) (all p<0.05). Higher Parkinson’s disease PRS was associated with thinner outer plexiform layer (p<0.001). Worse baseline cognitive performance was associated with thinner retinal nerve fibre layer (RNFL) (aOR=1.038, 95% CI (1.029 to 1.047), p<0.001) and photoreceptor (PR) segment (aOR=1.035, 95% CI (1.019 to 1.051), p<0.001), ganglion cell complex (aOR=1.007, 95% CI (1.002 to 1.013), p=0.004) and thicker ganglion cell layer (aOR=0.981, 95% CI (0.967 to 0.995), p=0.009), IPL (aOR=0.976, 95% CI (0.961 to 0.992), p=0.003), INL (aOR=0.923, 95% CI (0.905 to 0.941), p<0.001) and CSI (aOR=0.998, 95% CI (0.997 to 0.999), p<0.001). Worse future cognitive performance was associated with thicker IPL (aOR=0.945, 95% CI (0.915 to 0.999), p=0.045) and CSI (aOR=0.996, 95% CI (0.993 to 0.999) 95% CI, p=0.014). Prediction of cognitive decline was significantly improved with the addition of PRS and retinal measurements. Conclusions and relevance Retinal OCT measurements are significantly associated with genetic risk of neurodegenerative disease and may serve as biomarkers predictive of future cognitive impairment. Data are available upon reasonable request. Data is available from the UK Biobank.

中文翻译：

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视网膜光学相干断层扫描指标和多基因风险评分与认知功能和未来认知能力下降的关联

目的 评估视网膜光学相干断层扫描 (OCT) 测量和多基因风险评分 (PRS) 识别存在认知障碍风险的人群的潜力。方法 使用来自 50 342 名英国生物银行参与者的 OCT 图像，我们检查了视网膜层厚度与神经退行性疾病遗传风险之间的关联，并将这些指标与 PRS 相结合，以预测基线认知功能和未来认知恶化。多变量 Cox 比例风险模型用于预测认知表现。视网膜厚度分析的 P 值经过错误发现率调整。结果 较高的阿尔茨海默病 PRS 与较厚的内核层 (INL)、脉络膜-巩膜界面 (CSI) 和内丛状层 (IPL) 相关（所有 p<0.05）。较高的帕金森病 PRS 与较薄的外丛状层相关 (p<0.001)。较差的基线认知表现与较薄的视网膜神经纤维层 (RNFL)（aOR=1.038，95% CI（1.029 至 1.047），p<0.001）和感光器 (PR) 段（aOR=1.035，95% CI（1.019 至 1.047），p<0.001）相关。 1.051), p<0.001), 神经节细胞复合体 (aOR=1.007, 95% CI (1.002 - 1.013), p=0.004) 和较厚的神经节细胞层 (aOR=0.981, 95% CI (0.967 - 0.995), p= 0.009)、IPL (aOR=0.976, 95% CI (0.961 - 0.992), p=0.003)、INL (aOR=0.923, 95% CI (0.905 - 0.941), p<0.001) 和 CSI (aOR=0.998, 95) % CI（0.997 至 0.999），p<0.001）。更差的未来认知表现与较厚的 IPL（aOR=0.945，95% CI（0.915 至 0.999），p=0.045）和 CSI（aOR=0.996，95% CI（0.993 至 0.999）95% CI，p=0.014）相关。 。添加 PRS 和视网膜测量后，认知能力下降的预测得到显着改善。结论和相关性 视网膜 OCT 测量与神经退行性疾病的遗传风险显着相关，并且可以作为预测未来认知障碍的生物标志物。数据可根据合理要求提供。数据可从英国生物银行获得。