Gamma glutamyltransferase and risk of dementia in prediabetes and diabetes

Abstract

Diabetes is associated with cognitive impairment and greater risk for dementia, but the role of gammaglutamyltransferase (γ-GT) in dementia has not been elucidated. We determined incident dementia including Alzheimer's disease and vascular dementia, analyzing data from participants aged 40 years or older in the National Health Insurance Database, collected by the National Health Insurance Service in Korea, from January 2009 to December 2015. During a median follow-up of 7.6 years, 272,657 participants were diagnosed as having dementia. Higher serum γ-GT was associated with increased risk of dementia (HR = 1.22, 95% CI = 1.20-1.24), and had a strong positive association with early onset dementia (HR = 1.32, 95% CI = 1.24-1.40). An additive impact of higher γ-GT on dementia was observed regardless of glycemic status, and prevalent diabetes with the highest γ-GT quartile had a 1.8-fold increased dementia risk (HR = 1.82, 95% CI = 1.78-1.85). This effect of γ-GT concentration in diabetes was more prominent in individuals with vascular dementia (HR = 1.94, 95% CI = 1.84-2.04). In subgroup analysis, young age, male sex, and relatively healthy subjects with a higher γ-GT quartile had more increased dementia risk. In conclusion, γ-GT concentration as well as glycemic status could be a future risk factor for dementia in the general population.Over the past few decades, population aging has produced increased cases of dementia. Dementia is the leading cause of chronic disability in elderly individuals 1,2 . The worldwide prevalence of dementia was approximately 35.6 million in 2010, and the number of individuals living with dementia is expected to double every 20 years 3 . In addition, early onset dementia (EOD) can lead to significant socioeconomic burden and impaired quality of life in the younger population 4,5 , Along with genetic risk factors, inflammatory pathways and vascular factors have been implicated in the development of dementia. It is reported that chronic systemic inflammation could lead to cognitive dysfunction and substantially increase the risk of cognitive impairment 6 . Among chronic inflammatory diseases, diabetes is thought to play an important role in cognitive dysfunction 7 . Atherosclerosis is not only implicated in vascular dementia (VaD), but is also an independent risk factor for Alzheimer's disease (AD), which suggests its importance in dementia regardless of subtype 8 .Gamma-glutamyltransferase (γ-GT) is known as a marker of hepatobiliary disease 9 . γ-GT is a highly sensitive enzyme whose level may be elevated in liver disease such as non-alcoholic fatty liver disease (NAFLD). Recent studies demonstrate the possible role of γ-GT in systemic diseases; large population-based studies show the association between γ-GT and vascular disease 10,11 . Furthermore, correlations between γ-GT in inflammation 12 , and oxidation 13 have been demonstrated. In this context, it is plausible that elevated γ-GT in liver disease shares some common mechanisms in dementia. We hypothesized that γ-GT may be independ...

Cognitive Dysfunction in Non-Alcoholic Fatty Liver Disease—Current Knowledge, Mechanisms and Perspectives

“…One population-based study found that NAFLD was independently associated with a 16% increased risk of overall dementia (HR 1.22 for vascular dementia, HR 1.07 for AD) [ 124 ]. Another population-based study found that physically frail NAFLD patients with high risk of liver fibrosis were at a 5-fold increased risk of receiving a dementia diagnosis over a 8-year period, while physical frailty nor high risk of liver fibrosis were independent risk factors on their own [ 125 ].…”

Expression Status and Prognostic Significance of Gamma-Glutamyl Transpeptidase Family Genes in Hepatocellular Carcinoma

“…GGT is routinely utilized in clinical practice to assist clinicians in identifying the presence of liver injury. However, increased serum GGT is reported to be associated with metabolic syndrome (7), chronic kidney disease (8,9), dementia (10,11), and even malignant tumors (12). Recently, GGT has been demonstrated as the hallmark of oxidative stress; this enzyme can induce pro-oxidant reactions, which play an essential role in tumor formation and cell proliferation (13).…”

Risks and Prognoses of Alzheimer's Disease and Vascular Dementia in Patients With Insomnia: A Nationwide Population-Based Study

“…The date of dementia diagnosis was defined as the date when the prescription of an anti-dementia medication and registration of a dementia code coincided. The diagnostic criteria for dementia based on ICD-10 codes have been reported in previous studies (17,18). Among the entire national population, 8,080,619 patients diagnosed with insomnia between 2007 and 2014 were included in this study.…”