Department of Epidemiology, Gillings School of Global Public Health, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
Department of Biostatistics, Gillings School of Global Public Health, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
J Alzheimers Dis. 2021;79(4):1775-1784. doi: 10.3233/JAD-201241.
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.
To determine whether low levels of ALT and AST are associated with higher risk of incident dementia.
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.
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.
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.
生理范围内低水平的丙氨酸氨基转移酶（ALT）和天冬氨酸氨基转移酶（AST），作为肝脏代谢功能降低的替代标志物，与脑代谢减少、神经递质产生和突触维持受损以及痴呆患病率增加有关。目前尚不清楚低肝酶水平与痴呆发生之间是否存在前瞻性关联。
确定 ALT 和 AST 水平较低是否与痴呆发生风险增加相关。
在 1996-1998 年对 10100 名研究参与者（平均年龄 63.2 岁，55%为女性，22%为黑人）的血浆 ALT 和 AST 进行了测量。痴呆通过全面的神经心理学评估、年度联系和医疗记录监测来确定。使用 Cox 比例风险回归来估计相关性。
在中位随访 18.3 年（最长 21.9 年）期间，有 1857 人发生了痴呆。在调整了人口统计学因素后，较低水平的 ALT 和 AST 发生痴呆的发生率更高。与第二五分位相比，ALT 值低于第 10 个百分位数与痴呆风险增加相关（风险比 [HR] 1.34，95%置信区间 [CI] 1.08-1.65）。AST 的相应 HR 为 1.22（0.99-1.51）。
中年时生理范围内 ALT 和 AST 的低值（尤其是 ALT）与痴呆的长期风险增加相关，这表明需要关注肝脏功能在痴呆发病机制中的潜在作用。
