Department of Neurological Intensive Care Unit, Sixth Hospital of Shanxi Medical University (General Hospital of Tisco), Taiyuan, Shanxi, China.
Department of Neurology, First Hospital of Shanxi Medical University, Taiyuan, Shanxi, China.
PLoS One. 2024 Jul 23;19(7):e0306839. doi: 10.1371/journal.pone.0306839. eCollection 2024.
Although liver metabolic dysfunction has been found to potentially elevate susceptibility to cognitive impairment and dementia, there is still insufficient evidence to explore the non-linear association of liver enzymes with cognitive performance. Therefore, we aimed to elucidate the non-linear relationship between liver enzymes and cognitive performance.
In this cross-sectional study, 2764 individuals aged ≥ 60 who participated in the National Health and Nutrition Survey (NHANES) between 2011 and 2014 were included. The primary data comprised liver enzyme levels (alkaline phosphatase (ALP), aspartate aminotransferase (AST), alanine aminotransferase (ALT), AST/ALT ratio, and gamma-glutamyl transferase (GGT)), and cognitive performance was the major measured outcome. The associations were analyzed using weighted multivariate logistic regression, subgroup analysis, a generalized additive model, smooth fitting curves, and threshold effects.
The results of the fully adjusted model indicated that ALP was negatively associated with the animal fluency test (AFT) score (OR = 1.48, 95% CI: 1.11-1.98), whereas ALT demonstrated a positive association with the consortium to establish a registry for Alzheimer's disease (CERAD) test score (OR = 0.72, 95% CI: 0.53-0.97). Additionally, the AST/ALT ratio was negatively associated with the global cognitive test (OR = 2.39, 95% CI: 1.53-3.73), CERAD (OR = 2.61, 95% CI: 1.77-3.84), and digit symbol substitution test (DSST) scores (OR = 2.51, 95% CI: 1.57-4.02). GGT was also negatively associated with the AFT score (OR = 1.16, 95% CI: 1.01-1.33) in unadjusted model. A non-linear relationship was observed between liver enzymes and the risk of cognitive impairment as assessed by the global cognitive test. Specifically, when ALP > 60 U/L, 0.77 < AST/ALT < 1.76, and 25 < GGT < 94 U/L, higher liver enzyme levels were significantly associated with an elevated cognitive impairment risk, while a lower cognitive impairment risk when ALT level was > 17 U/L.
There is a non-linear relationship between liver enzymes and cognitive performance, indicating that liver enzyme levels should be maintained within a certain level to mitigate the risk of cognitive impairment.
尽管已经发现肝脏代谢功能障碍可能会增加认知障碍和痴呆的易感性，但仍缺乏足够的证据来探讨肝脏酶与认知表现之间的非线性关联。因此，我们旨在阐明肝脏酶与认知表现之间的非线性关系。
在这项横断面研究中，纳入了 2011 年至 2014 年间参加国家健康和营养调查（NHANES）的 2764 名年龄≥60 岁的个体。主要数据包括肝脏酶水平（碱性磷酸酶（ALP）、天冬氨酸氨基转移酶（AST）、丙氨酸氨基转移酶（ALT）、AST/ALT 比值和γ-谷氨酰转移酶（GGT）），认知表现是主要的测量结果。使用加权多变量逻辑回归、亚组分析、广义加性模型、平滑拟合曲线和阈值效应来分析关联。
完全调整模型的结果表明，ALP 与动物流畅性测试（AFT）评分呈负相关（OR=1.48，95%CI：1.11-1.98），而 ALT 与阿尔茨海默病协会注册中心（CERAD）测试评分呈正相关（OR=0.72，95%CI：0.53-0.97）。此外，AST/ALT 比值与全球认知测试（OR=2.39，95%CI：1.53-3.73）、CERAD（OR=2.61，95%CI：1.77-3.84）和数字符号替代测试（DSST）评分（OR=2.51，95%CI：1.57-4.02）呈负相关。在未调整模型中，GGT 与 AFT 评分也呈负相关（OR=1.16，95%CI：1.01-1.33）。肝脏酶与全球认知测试评估的认知障碍风险之间存在非线性关系。具体而言，当 ALP＞60U/L、0.77＜AST/ALT＜1.76 和 25＜GGT＜94U/L 时，较高的肝脏酶水平与认知障碍风险升高显著相关，而当 ALT 水平＞17U/L 时，认知障碍风险较低。
肝脏酶与认知表现之间存在非线性关系，表明应将肝脏酶水平维持在一定水平以降低认知障碍的风险。
