Gamma-Glutamyltransferase (GGT) as a biomarker of cognitive decline at the end of life: contrasting age and time to death trajectories

Björk, Marcus Praetorius; Johansson, Boo

doi:10.1017/s1041610217002393

Cited by 22 publications

(17 citation statements)

References 26 publications

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“…Kunutsor and Laukkanen 16 demonstrated for the first time that elevated GGT level in midlife is associated with risk of dementia in the male population aged 42 to 61 years in Finland. Praetorius Bjork and Johansson 17 also reported the association among GGT, cognitive performance, and dementia in late life. Nevertheless, these studies included limited populations, such as male or elderly only cohorts, with relatively small sizes, and did not account for variability in GGT.…”

Section: Introductionmentioning

confidence: 95%

Gamma‐glutamyl transferase variability and risk of dementia: A nationwide study

Lee

Han

Park

et al. 2020

Int J Geriat Psychiatry

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Objectives 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. Methods 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). Results 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)]. Conclusions 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.

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Section: Introductionmentioning

confidence: 95%

Gamma‐glutamyl transferase variability and risk of dementia: A nationwide study

Lee

Han

Park

et al. 2020

Int J Geriat Psychiatry

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“…On correction for regression dilution, the corresponding estimates were respectively 1.51 and 1.37 per 1 SD increase in long-term serum GGT. In another recent longitudinal study conducted in older individuals, Praetorius Björk and Johansson demonstrated higher GGT concentrations to be associated with cognitive decline prior to death and vascular dementia in late life ( Praetorius Bjork and Johansson, 2017 ).…”

Section: Introductionmentioning

confidence: 99%

Genetically elevated gamma-glutamyltransferase and Alzheimer's disease

Kunutsor¹,

Laukkanen

Burgess

2018

Experimental Gerontology

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Observational epidemiological evidence supports a linear and independent association between serum gamma-glutamyltransferase (GGT) concentrations and the risk of Alzheimer's disease (AD). However, the causality of this association has not been previously investigated. We sought to assess the causal nature of this association using a Mendelian randomization (MR) approach. Using inverse-variance weighted MR analysis, we assessed the association between GGT and AD using summary statistics for single nucleotide polymorphism (SNP)-AD associations obtained from the International Genomics of Alzheimer's Project of 17,008 individuals with AD and 37,154 controls. We used 26 SNPs significantly associated with GGT in a previous genome-wide association study on liver enzymes as instruments. Sensitivity analyses to account for potential genetic pleiotropy included MR-Egger and weighted median MR. The odds ratio of AD was 1.09 (95% confidence interval, 0.98 to 1.22; p = 0.10) per one standard deviation genetically elevated GGT based on all 26 SNPs. The results were similar in both MR-Egger and weighted median MR methods. Overall, our findings cannot confirm a strong causal effect of GGT on AD risk. Further MR investigations using individual-level data are warranted to confirm or rule out causality.

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“…It is suggested that serum GGT within the normal range is an early marker for oxidative stress (34). Oxidative stress has been suggested to be associated with frailty (35) and increased GGT levels in later life (80 years and older) were associated with cognitive decline (36). However, we unexpectedly observed lower instead of higher GGT levels in cognitively frail women compared to controls, indicating that cognitive frail women might have less oxidative stress.…”

Section: Discussionmentioning

confidence: 99%

Trajectories of (Bio)markers During the Development of Cognitive Frailty in the Doetinchem Cohort Study

et al. 2019

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Background: Long-term changes in (bio)markers for cognitive frailty are not well characterized. Therefore, our aim is to explore (bio)marker trajectories in adults who became cognitively frail compared to age- and sex-matched controls who did not become cognitively frail over a 15 year follow-up. We hypothesize that those who become cognitively frail have more unfavorable trajectories of (bio)markers compared to controls. Methods: The Doetinchem Cohort Study is a longitudinal population-based study that started in 1987–1991 in men and women aged 20–59 years, with follow-up examinations every 5 years. For the current analyses, we used data of 17 potentially relevant (bio)markers (e.g., body mass index (BMI), urea) from rounds 2 to 5 (1993–2012). A global cognitive functioning score (based on memory, speed, and flexibility) was calculated for each round and transformed into education and examination round-adjusted z-scores. The z-score that corresponded to the 10th percentile in round 5 (z-score = −0.77) was applied as cut-off point for incident cognitive frailty in rounds 2–5. In total, 455 incident cognitively frail cases were identified retrospectively and were compared with 910 age- and sex-matched controls. Trajectories up to 15 years before and 10 years after incident cognitive frailty were analyzed using generalized estimating equations with stratification for sex and adjustment for age and, if appropriate, medication use. Results were further adjusted for level of education, depressive symptoms, BMI, and lifestyle factors. Results: In men, (bio)marker trajectories did not differ as they ran parallel and the difference in levels was not statistically significant between those who became cognitively frail compared to controls. In women, total cholesterol trajectories first increased and thereafter decreased in cognitively frail women and steadily increased in controls, gamma-glutamyltransferase trajectories were more or less stable in cognitively frail women and increased in controls, and urea trajectories increased in cognitively frail women and remained more or less stable in controls. Results were similar after additional adjustment for potential confounders. Conclusions: Out of the 17 (bio)markers included in this explorative study, differential trajectories for three biomarkers were observed in women. We do not yet consider any of the studied (bio)markers as promising biomarkers for cognitive frailty.

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Gamma-Glutamyltransferase (GGT) as a biomarker of cognitive decline at the end of life: contrasting age and time to death trajectories

Abstract: This is the first longitudinal study to report on significant associations in late life between GGT, cognitive performance and dementia. Further research is needed to examine the underlying mechanisms of GGT as a marker of age-related cognitive decline.

Cited by 22 publications

References 26 publications

Gamma‐glutamyl transferase variability and risk of dementia: A nationwide study

Gamma‐glutamyl transferase variability and risk of dementia: A nationwide study

Genetically elevated gamma-glutamyltransferase and Alzheimer's disease

Trajectories of (Bio)markers During the Development of Cognitive Frailty in the Doetinchem Cohort Study

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