Sex-specific associations between estimated glucose disposal rate and cognitive decline in middle-aged and older adults in China: a longitudinal cohort study

BackgroundInsulin resistance (IR) is recognized as a potential modifiable risk factor for cognitive decline, but findings within Asian populations have been inconsistent. Given the high prevalence of dementia and its substantial economic burden in China, large-scale longitudinal studies are essentia...

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Main Authors: Chun Luo, Shuang Han, Xiaoying Shen, Hao Wu, Jianqing Zhou, Bingyang Liu
Format: Article
Language:English
Published: Frontiers Media S.A. 2025-02-01
Series:Frontiers in Aging Neuroscience
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Online Access:https://www.frontiersin.org/articles/10.3389/fnagi.2025.1544352/full
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author Chun Luo
Shuang Han
Xiaoying Shen
Hao Wu
Jianqing Zhou
Bingyang Liu
author_facet Chun Luo
Shuang Han
Xiaoying Shen
Hao Wu
Jianqing Zhou
Bingyang Liu
author_sort Chun Luo
collection DOAJ
description BackgroundInsulin resistance (IR) is recognized as a potential modifiable risk factor for cognitive decline, but findings within Asian populations have been inconsistent. Given the high prevalence of dementia and its substantial economic burden in China, large-scale longitudinal studies are essential to elucidate the complex relationship between IR and cognitive function.MethodsThis longitudinal cohort study included 8,734 middle-aged and older adults (median age: 58 years; 53.6% females) from the China Health and Retirement Longitudinal Study (CHARLS), followed from 2011 to 2018. Estimated glucose disposal rate (eGDR) was used to assess IR and was calculated using waist circumference, hypertension status, and HbA1c levels. Participants were categorized into tertiles based on eGDR levels (Tertile 1: lowest; Tertile 3: highest). Cognitive function was calculated as the sum of episodic memory and executive function scores, which was then standardized to a Z-score. Linear mixed-effects models and dose-response analyses were performed to evaluate the association between baseline eGDR and cognitive changes in the total population and stratified by sex.ResultsHigher eGDR levels were significantly associated with slower global cognitive decline (Tertile 3 vs. Tertile 1: β = 0.007; 95% CI: 0.000–0.014; P = 0.047). This association was stronger in females (Tertile 3 vs. Tertile 1: β = 0.011; 95% CI: 0.002–0.021; P = 0.021), while no significant association was observed in males. Dose-response analyses indicated a linear positive relationship between baseline eGDR and global cognitive function in the total population and in females, but not in males. Similar patterns were found for episodic memory and executive function, with significant associations predominantly in females.ConclusionHigher eGDR was significantly associated with slower cognitive decline, particularly among women. These findings underscore the potential of eGDR as a marker for identifying and mitigating cognitive decline and highlight the importance of sex-specific strategies to address insulin resistance and promote cognitive health.
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spelling doaj-art-ab0dab80313044fd84a3d5d6f162a62f2025-02-05T07:32:04ZengFrontiers Media S.A.Frontiers in Aging Neuroscience1663-43652025-02-011710.3389/fnagi.2025.15443521544352Sex-specific associations between estimated glucose disposal rate and cognitive decline in middle-aged and older adults in China: a longitudinal cohort studyChun Luo0Shuang Han1Xiaoying Shen2Hao Wu3Jianqing Zhou4Bingyang Liu5Ningbo Medical Center Lihuili Hospital, Ningbo University, Ningbo, ChinaAffiliated Hangzhou First People’s Hospital, School of Medicine, Westlake University, Hangzhou, ChinaNingbo Medical Center Lihuili Hospital, Ningbo University, Ningbo, ChinaNingbo Medical Center Lihuili Hospital, Ningbo University, Ningbo, ChinaNingbo Medical Center Lihuili Hospital, Ningbo University, Ningbo, ChinaNingbo Medical Center Lihuili Hospital, Ningbo University, Ningbo, ChinaBackgroundInsulin resistance (IR) is recognized as a potential modifiable risk factor for cognitive decline, but findings within Asian populations have been inconsistent. Given the high prevalence of dementia and its substantial economic burden in China, large-scale longitudinal studies are essential to elucidate the complex relationship between IR and cognitive function.MethodsThis longitudinal cohort study included 8,734 middle-aged and older adults (median age: 58 years; 53.6% females) from the China Health and Retirement Longitudinal Study (CHARLS), followed from 2011 to 2018. Estimated glucose disposal rate (eGDR) was used to assess IR and was calculated using waist circumference, hypertension status, and HbA1c levels. Participants were categorized into tertiles based on eGDR levels (Tertile 1: lowest; Tertile 3: highest). Cognitive function was calculated as the sum of episodic memory and executive function scores, which was then standardized to a Z-score. Linear mixed-effects models and dose-response analyses were performed to evaluate the association between baseline eGDR and cognitive changes in the total population and stratified by sex.ResultsHigher eGDR levels were significantly associated with slower global cognitive decline (Tertile 3 vs. Tertile 1: β = 0.007; 95% CI: 0.000–0.014; P = 0.047). This association was stronger in females (Tertile 3 vs. Tertile 1: β = 0.011; 95% CI: 0.002–0.021; P = 0.021), while no significant association was observed in males. Dose-response analyses indicated a linear positive relationship between baseline eGDR and global cognitive function in the total population and in females, but not in males. Similar patterns were found for episodic memory and executive function, with significant associations predominantly in females.ConclusionHigher eGDR was significantly associated with slower cognitive decline, particularly among women. These findings underscore the potential of eGDR as a marker for identifying and mitigating cognitive decline and highlight the importance of sex-specific strategies to address insulin resistance and promote cognitive health.https://www.frontiersin.org/articles/10.3389/fnagi.2025.1544352/fullestimated glucose disposal ratecognitive declineinsulin resistancesex differenceslongitudinal analysis
spellingShingle Chun Luo
Shuang Han
Xiaoying Shen
Hao Wu
Jianqing Zhou
Bingyang Liu
Sex-specific associations between estimated glucose disposal rate and cognitive decline in middle-aged and older adults in China: a longitudinal cohort study
Frontiers in Aging Neuroscience
estimated glucose disposal rate
cognitive decline
insulin resistance
sex differences
longitudinal analysis
title Sex-specific associations between estimated glucose disposal rate and cognitive decline in middle-aged and older adults in China: a longitudinal cohort study
title_full Sex-specific associations between estimated glucose disposal rate and cognitive decline in middle-aged and older adults in China: a longitudinal cohort study
title_fullStr Sex-specific associations between estimated glucose disposal rate and cognitive decline in middle-aged and older adults in China: a longitudinal cohort study
title_full_unstemmed Sex-specific associations between estimated glucose disposal rate and cognitive decline in middle-aged and older adults in China: a longitudinal cohort study
title_short Sex-specific associations between estimated glucose disposal rate and cognitive decline in middle-aged and older adults in China: a longitudinal cohort study
title_sort sex specific associations between estimated glucose disposal rate and cognitive decline in middle aged and older adults in china a longitudinal cohort study
topic estimated glucose disposal rate
cognitive decline
insulin resistance
sex differences
longitudinal analysis
url https://www.frontiersin.org/articles/10.3389/fnagi.2025.1544352/full
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