Division of Endocrinology and Metabolism, Department of Internal Medicine, Korea University College of Medicine, Seoul, Republic of Korea.
Department of Biostatistics, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea.
Int J Geriatr Psychiatry. 2020 Oct;35(10):1105-1114. doi: 10.1002/gps.5332. Epub 2020 Jul 19.
Variability in various biomarkers has emerged as a new clinical indicator for diseases including neurodegenerative disorders. Gamma-glutamyl transferase (GGT) has a potential to be involved in the pathogenesis of dementia due to its function as a marker of oxidative stress and atherosclerosis. We investigated the association between baseline GGT, GGT variability, and dementia risk for the first time in a large population.
The Korean National Health Insurance Service datasets of claims and preventive health check-ups from 2004 to 2016 were used for this retrospective longitudinal study. The risk of incident dementia (all-cause dementia, Alzheimer's disease, and vascular dementia) was analyzed according to sex-specific quartiles of baseline GGT and GGT variability, and groups categorized by baseline GGT and GGT variability in ≥40-year-old individuals without baseline dementia (N = 6 046 442; mean follow-up 6.32 years).
During follow-up, 166 851 cases of new dementia developed. The fully adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) for incident dementia increased in the higher quartiles of baseline GGT and GGT variability (HR [95% CI]: Q2, 1.034 [1.019-1.049]; Q3, 1.090 [1.075-1.105]; Q4, 1.212 [1.196-1.229]). The association between GGT variability quartiles and dementia risk remained significant even after adjusting for log-transformed baseline GGT level. The fully adjusted HRs for dementia was highest in the group with high baseline GGT concentration and the highest GGT variability quartile [HR (95% CI): 1.273 (1.250-1.296)].
Not only baseline GGT level, but also GGT variability may be an independent predictor of dementia, and might be used for risk stratification for future dementia.
各种生物标志物的变异性已成为包括神经退行性疾病在内的多种疾病的新临床指标。由于 γ-谷氨酰转移酶 (GGT) 作为氧化应激和动脉粥样硬化的标志物，因此它有可能参与痴呆症的发病机制。我们首次在大型人群中研究了基线 GGT、GGT 变异性与痴呆风险之间的关系。
本回顾性纵向研究使用了 2004 年至 2016 年的韩国国家健康保险服务索赔和预防健康检查数据集。根据基线 GGT 和 GGT 变异性的性别特异性四分位距，以及无基线痴呆症的≥40 岁个体的基线 GGT 和 GGT 变异性分组（N=6046442；平均随访 6.32 年），分析了痴呆症（所有原因痴呆症、阿尔茨海默病和血管性痴呆症）的发病风险。
在随访期间，有 166851 例新发痴呆症。在基线 GGT 和 GGT 变异性较高的四分位距中，新发痴呆症的全调整危险比（HR）和 95%置信区间（CI）均增加（HR[95%CI]：Q2，1.034[1.019-1.049]；Q3，1.090[1.075-1.105]；Q4，1.212[1.196-1.229]）。即使调整了基线 GGT 水平的对数转换后，GGT 变异性四分位距与痴呆症风险之间的关联仍然显著。在基线 GGT 浓度高且 GGT 变异性四分位距最高的组中，痴呆症的全调整 HR 最高[HR（95%CI）：1.273（1.250-1.296）]。
基线 GGT 水平升高和 GGT 变异性增加均可能是痴呆的独立预测因素，并且可能用于未来痴呆症的风险分层。
