Graduate Institute of Biomedical Sciences, China Medical University, Taichung, Taiwan; Department of Psychiatry & Brain Disease Research Center, China Medical University Hospital, Taichung, Taiwan; Department of Psychology, College of Medical and Health Sciences, Asia University, Taichung, Taiwan.
National Center for Geriatrics and Welfare Research, National Health Research Institutes, Yunlin, Taiwan; College of Public Health, China Medical University, Taichung, Taiwan.
Psychiatry Res. 2023 Aug;326:115288. doi: 10.1016/j.psychres.2023.115288. Epub 2023 Jun 10.
NMDAR hypofunction and oxidative stress are implicated in the pathogenesis of Alzheimer's disease. D-amino acid oxidase (DAO) regulates NMDAR function. Glutathione, superoxide dismutase, and catalase are three first-line endogenous antioxidants. This study explored the associations of these potential biomarkers with mild cognitive impairment. Cognitive function and blood levels of DAO, glutathione, superoxide dismutase, and catalase were measured in 63 mild cognitive impairment patients and 24 healthy individuals every 6 months for 2 years. Among the patients, DAO and glutathione levels at baseline contributed to the cognitive decline 2 years later. Among the healthy individuals, only glutathione levels were associated with cognitive change. The four biomarkers differed in change directions (upward vs. downward) in the patients and in the healthy individuals. Among patients, glutathione levels were negatively correlated with superoxide dismutase and positively correlated with catalase, and DAO levels were negatively correlated with superoxide dismutase. To our knowledge, this is the first study to demonstrate the differential associations of NMDAR hypofunction and oxidative stress with cognitive change between the mild cognitive impairment patients and healthy people. Glutathione may be regarded as an aging marker for both mild cognitive impairment and normal aging; and DAO, a biomarker exclusively for mild cognitive impairment.
N-甲基-D-天冬氨酸受体（NMDAR）功能低下和氧化应激与阿尔茨海默病的发病机制有关。D-氨基酸氧化酶（DAO）调节 NMDAR 功能。谷胱甘肽、超氧化物歧化酶和过氧化氢酶是三种一线内源性抗氧化剂。本研究探讨了这些潜在生物标志物与轻度认知障碍的相关性。在 2 年内，每隔 6 个月对 63 名轻度认知障碍患者和 24 名健康个体进行认知功能和血液 DAO、谷胱甘肽、超氧化物歧化酶和过氧化氢酶水平的测量。在患者中，基线时的 DAO 和谷胱甘肽水平与 2 年后的认知下降有关。在健康个体中，只有谷胱甘肽水平与认知变化相关。这四个生物标志物在患者和健康个体中的变化方向（上升与下降）不同。在患者中，谷胱甘肽水平与超氧化物歧化酶呈负相关，与过氧化氢酶呈正相关，而 DAO 水平与超氧化物歧化酶呈负相关。据我们所知，这是第一项表明 NMDAR 功能低下和氧化应激与轻度认知障碍患者和健康人群认知变化之间存在差异相关性的研究。谷胱甘肽可能被视为轻度认知障碍和正常衰老的衰老标志物；而 DAO 则是轻度认知障碍的特异性生物标志物。
