Li Wei, Yue Ling, Sun Lin, Xiao Shifu
Department of Geriatric Psychiatry, Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Alzheimer's Disease and Related Disorders Center, Shanghai Jiao Tong University, Shanghai, China.
Front Med (Lausanne). 2022 Apr 7;9:780174. doi: 10.3389/fmed.2022.780174. eCollection 2022.
Recent Alzheimer's disease (AD) hypotheses implicate that hepatic metabolic disorders might contribute to the disease pathogenesis of AD, but the mechanism remains unclear.
To investigate whether the elevated aspartate aminotransferase (AST) and Alanine aminotransferase (ALT) ratio is associated with future cognitive decline, and to explore the possible mechanisms of liver enzymes affecting cognitive function.
Three different clinical cohorts were included in the current study, including one cross-sectional study (Cohort 1) and two longitudinal follow-up studies (Cohort 2 and 3). All participants completed a detailed clinical evaluation, neuropsychological tests, and liver enzyme tests. In addition, some of them also underwent structural magnetic resonance imaging (MRI) scans.
Cohort 1 was derived from the CRC2017ZD02 program, including 135 amnestic mild cognitive impairment (aMCI) patients, 22 AD patients, and 319 normal controls. In this cross-sectional study, we found that the AST/ALT ratio was associated with AD ( = 0.014, OR = 1.848, 95%CI: 1.133∼3.012), but not aMCI; Cohort 2 was derived from the Shanghai Brain Health Program. A total of 260 community elderly people with normal cognitive function were included in the study and followed up for 2 years. In this 2-year longitudinal follow-up study, we found that a higher AST/ALT ratio was a risk factor for future development of aMCI ( = 0.014, HR = 1.848, 95%CI: 1.133∼3.021); Cohort 3 was derived from the China longitudinal aging study (CLAS) Program. A total of 94 community elderly people with normal cognitive function were followed up for 7 years, and all of them completed MRI scans. In this 7-year longitudinal follow-up study, we found that a higher AST/ALT ratio was a risk factor for future development of aMCI ( = 0.006, HR = 2.247, 95%CI: 1.248∼4.049), and the AST/ALT ratio was negatively correlated with right hippocampal volume ( = -0.148, = 0.043).
An increased ratio of AST to ALT is associated with a higher risk of cognitive impairment and may impair cognitive function by affecting hippocampal volume.
近期的阿尔茨海默病（AD）假说认为，肝脏代谢紊乱可能在AD的发病机制中起作用，但其机制尚不清楚。
探讨天冬氨酸转氨酶（AST）与丙氨酸转氨酶（ALT）比值升高是否与未来认知功能下降相关，并探讨肝酶影响认知功能的可能机制。
本研究纳入了三个不同的临床队列，包括一项横断面研究（队列1）和两项纵向随访研究（队列2和队列3）。所有参与者均完成了详细的临床评估、神经心理学测试和肝酶测试。此外，部分参与者还接受了结构磁共振成像（MRI）扫描。
队列1来自CRC2017ZD02项目，包括135例遗忘型轻度认知障碍（aMCI）患者、22例AD患者和319例正常对照。在这项横断面研究中，我们发现AST/ALT比值与AD相关（P = 0.014，OR = 1.848，95%CI：1.133～3.012），但与aMCI无关；队列2来自上海脑健康项目。共纳入260例认知功能正常的社区老年人，并随访2年。在这项为期2年的纵向随访研究中，我们发现较高的AST/ALT比值是未来发生aMCI的危险因素（P = 0.014，HR = 1.848，95%CI：1.133～3.021）；队列3来自中国纵向衰老研究（CLAS）项目。共纳入94例认知功能正常的社区老年人，随访7年，所有参与者均完成了MRI扫描。在这项为期7年的纵向随访研究中，我们发现较高的AST/ALT比值是未来发生aMCI的危险因素（P = 0.006，HR = 2.247，95%CI：1.248～4.049），且AST/ALT比值与右侧海马体积呈负相关（r = -0.148，P = 0.043）。
AST与ALT比值升高与认知障碍风险增加相关，可能通过影响海马体积损害认知功能。
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