Aier Academy of Ophthalmology, Central South University, No. 188 South Furong Road, Tianxin District, Changsha 410015, Hunan, P.R. China.
Department of Glaucoma, Changsha Aier Eye Hospital, No. 188 South Furong Road, Tianxin District, Changsha 410015, Hunan, P.R. China.
Cereb Cortex. 2024 Sep 3;34(9). doi: 10.1093/cercor/bhae385.
Glaucoma and Alzheimer's disease are critical degenerative neuropathies with global impact. Previous studies have indicated that glaucomatous damage could extend beyond ocular structures, leading to brain alterations potentially associated with Alzheimer's disease risk. This study aimed to explore the causal associations among glaucoma, brain alterations, and Alzheimer's disease. We conducted a comprehensive investigation into the genetic correlation and causality between glaucoma, glaucoma endophenotypes, cerebral cortical surficial area and thickness, and Alzheimer's disease (including late-onset Alzheimer's disease, cognitive performance, and reaction time) using linkage disequilibrium score regression and Mendelian randomization. This study showed suggestive genetic correlations between glaucoma, cortical structures, and Alzheimer's disease. The genetically predicted all-caused glaucoma was nominally associated with a decreased risk of Alzheimer's disease (OR = 0.96, 95% CI: 0.93-0.99, P = 0.013). We found evidence for suggestive causality between glaucoma (endophenotypes) and 20 cortical regions and between 29 cortical regions and Alzheimer's disease (endophenotypes). Four cortical regions were causally associated with cognitive performance or reaction time at a significant threshold (P < 6.2E-04). Thirteen shared cortical regions between glaucoma (endophenotypes) and Alzheimer's disease (endophenotypes) were identified. Our findings complex causal relationships among glaucoma, cerebral cortical structures, and Alzheimer's disease. More studies are required to clarify the mediation effect of cortical alterations in the relationship between glaucoma and Alzheimer's disease.
青光眼和阿尔茨海默病是具有全球影响的两种关键退行性神经病变。先前的研究表明，青光眼损害可能超出眼组织结构，导致与阿尔茨海默病风险相关的潜在脑改变。本研究旨在探讨青光眼、脑改变和阿尔茨海默病之间的因果关系。我们使用连锁不平衡评分回归和孟德尔随机化，对青光眼、青光眼表型、大脑皮质表面积和厚度以及阿尔茨海默病（包括晚发性阿尔茨海默病、认知表现和反应时间）之间的遗传相关性和因果关系进行了全面研究。本研究表明青光眼、皮质结构和阿尔茨海默病之间存在提示性的遗传相关性。全因青光眼的遗传预测与阿尔茨海默病风险降低有关（OR=0.96，95%CI：0.93-0.99，P=0.013）。我们发现青光眼（表型）与 20 个皮质区域之间以及 29 个皮质区域与阿尔茨海默病（表型）之间存在提示性因果关系。四个皮质区域与认知表现或反应时间之间存在因果关系，达到了显著阈值（P<6.2E-04）。青光眼（表型）和阿尔茨海默病（表型）之间有 13 个共享皮质区域。我们的研究结果揭示了青光眼、大脑皮质结构和阿尔茨海默病之间复杂的因果关系。需要进一步的研究来阐明皮质改变在青光眼和阿尔茨海默病之间关系中的中介作用。
