Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2025 Jul 1;15(1):20928.
doi: 10.1038/s41598-025-06439-2.

A cross sectional study of the diabetes mediated GGT to HDL ratio and cognitive function in older adults

Ye Wang  1   2 , Yanping Mao  2 , Tianmei Xu  1 , Lujie Han  3 , Wenxuan Zhang  1 , Wangdi Sun  4 , Jiaxi Xu  5 , Enyan Yu  6
Affiliations

A cross sectional study of the diabetes mediated GGT to HDL ratio and cognitive function in older adults

Ye Wang et al. Sci Rep. .

Abstract

The rising incidence of cognitive disorders has become a significant challenge in global public health. The ratio of Gamma-glutamyl transferase (GGT) to high-density lipoprotein (HDL), associated with insulin resistance, has an unclear relationship with cognitive function. Our cross-sectional study utilized data from the NHANES database, employing the digit symbol substitution test (DSST) to assess cognitive ability. We conducted weighted linear regression, weighted mediation analysis, dose-response relationships, and subgroup analyses to investigate the link between the GGT/HDL ratio and DSST scores, with a particular focus on the mediating role of diabetes. The study included 2750 participants. After adjusting for covariates, we found that a higher GGT/HDL ratio was significantly correlated with lower DSST scores (β = -0.06, 95% CI -0.08 to -0.04, P < 0.001, P for non-linear = 0.169), and diabetes mediated the relationship between the GGT/HDL ratio and DSST scores, accounting for 13.8% of the total effect (P = 0.034). These findings suggest that in the U.S. population aged 60 and above, an increased GGT/HDL ratio is associated with an increased risk of cognitive decline, with diabetes playing a mediating role in this association.

Keywords: Cognitive impairment; Diabetes mellitus; GGT/HDL ratio; Gamma-glutamyl transferase; High-density lipoprotein; NHANES.

PubMed Disclaimer

Conflict of interest statement

Declarations. Competing interests: The authors declare no competing interests.

Figures

Fig. 1
Fig. 1
Association between GGT/HDL and cognitive performance in DSST. Solid lines and filled ranges indicate predictive values and 95% confidence intervals. Adjusted for age, gender, race, education level, married status, BMI, smoking status, alcohol status, high cholesterol, liver conditions.
Fig. 2
Fig. 2
The mediating effect of diabetes on the relationship between GGT/HDL and DSST in elderly adults.
Fig. 3
Fig. 3
Forest plot showing the subgroup analysis for the association between GGT/HDL and the DSST scores.
Fig. 4
Fig. 4
Flow chart of participant selection.
See this image and copyright information in PMC

References

    1. Estimation of the global prevalence of dementia. In 2019 and forecasted prevalence in 2050: an analysis for the global burden of disease study 2019. Lancet Public. Health7, e105–e125 (2022). - PMC - PubMed
    1. Weng, X. et al. Association between mixed exposure of phthalates and cognitive function among the U.S. Elderly from NHANES 2011–2014: three statistical models. Sci. Total Environ.828, 154362 (2022). - PubMed
    1. Alzheimer’s disease facts and figures. Alzheimers Dement10.1002/alz.13016 (2023).
    1. Morató, X. et al. A randomized, open-label clinical trial in mild cognitive impairment with EGb 761 examining blood markers of inflammation and oxidative stress. Sci. Rep.13, 5406 (2023). - PMC - PubMed
    1. Gaikwad, S., Senapati, S., Haque, M. A. & Kayed, R. Senescence, brain inflammation, and oligomeric Tau drive cognitive decline in alzheimer’s disease: evidence from clinical and preclinical studies. Alzheimers Dement.20, 709–727 (2024). - PMC - PubMed

Substances