Background:Low levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) in the low physiologic range, surrogate markers for reduced liver metabolic function, are associated with cerebral hypometabolism, impairment in neurotransmitter production and synaptic maintenance, and a higher prevalence of dementia. It is unknown whether a prospective association exists between low liver enzyme levels and incident dementia. Objective:To determine whether low levels of ALT and AST are associated with higher risk of incident dementia. Methods:Plasma ALT and AST were measured on 10,100 study participants (mean age 63.2 years, 55% female, 22% black) in 1996–1998. Dementia was ascertained from comprehensive neuropsychological assessments, annual contact, and medical record surveillance. Cox proportional hazards regression was used to estimate the association. Results:During a median follow-up of 18.3 years (maximum 21.9 years), 1,857 individuals developed dementia. Adjusted for demographic factors, incidence rates of dementia were higher at the lower levels of ALT and AST. Compared to the second quintile, ALT values <10th percentile were associated with a higher risk of dementia (hazard ratio [HR] 1.34, 95% CI 1.08–1.65). The corresponding HR was 1.22 (0.99–1.51) for AST. Conclusion:Plasma aminotransferases <10th percentile of the physiologic range at mid-life, particularly ALT, were associated with greater long-term risk of dementia, advocating for attention to the putative role of hepatic function in the pathogenesis of dementia.

中文翻译：

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低肝酶和痴呆风险：社区动脉粥样硬化风险 (ARIC) 研究


背景：丙氨酸氨基转移酶 (ALT) 和天冬氨酸氨基转移酶 (AST) 水平处于低生理范围，是肝脏代谢功能降低的替代标志物，与脑代谢低下、神经递质生成和突触维持受损以及痴呆症患病率较高有关。目前尚不清楚低肝酶水平与痴呆症之间是否存在前瞻性关联。目的：确定低水平的 ALT 和 AST 是否与较高的痴呆风险相关。方法：1996-1998 年测量了 10,100 名研究参与者（平均年龄 63.2 岁，55% 女性，22% 黑人）的血浆 ALT 和 AST。痴呆症是通过全面的神经心理学评估、年度接触和病历监测来确定的。使用 Cox 比例风险回归来估计相关性。结果：在中位随访 18.3 年（最长 21.9 年）期间，1,857 人患上了痴呆症。调整人口因素后，ALT 和 AST 水平较低时痴呆症的发病率较高。与第二个五分位数相比，ALT 值<10% 与较高的痴呆风险相关（风险比 [HR] 1.34，95% CI 1.08-1.65）。 AST 相应的 HR 为 1.22 (0.99–1.51)。结论：中年时生理范围的血浆转氨酶<10%，尤其是 ALT，与较大的长期痴呆风险相关，提倡关注肝功能在痴呆发病机制中的假定作用。