Emory Univeristy, 1841 Clifton Road NE, Atlanta, GA, 30329, United States.
J Neuroinflammation. 2018 Jan 16;15(1):17. doi: 10.1186/s12974-017-1026-z.
Redox signaling, which can be assessed by circulating aminothiols, reflects oxidative stress (OS) status and has been linked to clinical cardiovascular disease and its risk factors. These, in turn, are related to executive function decline. OS may precede the pro-inflammatory state seen in vascular disease. The objective of this study is to investigate the association between aminothiol markers of OS and inflammation in cognitive decline, especially in the executive cognitive domain which is highly susceptible to cardiovascular risk factors and is an important predictor of cognitive disability.
The study design is that of a longitudinal cohort study within the setting of a large academic institution with participants being university employees (n = 511), mean age 49 years, 68% women, and 23% African-American. These participants were followed for four consecutive years with a yearly cognitive assessment conducted using computerized versions of 15 cognitive tests. Peripheral cystine, glutathione, their disulfide derivatives, and C-reactive protein (CRP) were measured.
Lower levels of glutathione at baseline was associated with a decline in the executive domain over 4 years (covariate-adjusted relative risk (RR) for glutathione = 1.70 (95% CI = 1.02-2.85), p = 0.04). Furthermore, a longitudinal decline in glutathione level was associated with a faster decline in the executive domain (p = 0.03). None of the other OS markers or CRP were linked to cognitive decline over 4 years.
Increased OS reflected by decreased glutathione was associated with a decline in executive function in a healthy population. In contrast, inflammation was not linked to cognitive decline. OS may be an earlier biomarker that precedes the inflammatory phase of executive decline with aging.
氧化还原信号（可通过循环氨基硫醇评估）反映氧化应激（OS）状态，并与临床心血管疾病及其危险因素相关。这些因素又与执行功能下降有关。OS 可能先于血管疾病中出现的促炎状态。本研究旨在探讨 OS 的氨基硫醇标志物与认知能力下降之间的关联，特别是在执行认知领域，该领域易受心血管危险因素影响，是认知障碍的重要预测指标。
本研究设计为在大型学术机构环境中进行的纵向队列研究，参与者为大学员工（n=511），平均年龄 49 岁，68%为女性，23%为非裔美国人。这些参与者被随访 4 年，每年进行一次计算机化的 15 项认知测试评估。测量外周胱氨酸、谷胱甘肽、其二硫化物衍生物和 C 反应蛋白（CRP）。
基线时谷胱甘肽水平较低与 4 年内执行域下降相关（谷胱甘肽的校正后相对风险（RR）=1.70（95%CI=1.02-2.85），p=0.04）。此外，谷胱甘肽水平的纵向下降与执行域下降速度加快相关（p=0.03）。其他 OS 标志物或 CRP 均与 4 年内认知能力下降无关。
氧化还原状态增加（表现为谷胱甘肽减少）与健康人群执行功能下降相关。相反，炎症与认知能力下降无关。OS 可能是一种早期生物标志物，先于衰老时执行能力下降的炎症阶段。
