Sex-Specific Associations Between Estimated Glucose Disposal Rate and Cognitive Decline in Middle-Aged and Older Adults in China: A Longitudinal Cohort Study

Chun Luo ¹ Shuang Han ² Xiaoying Shen ¹ Hao Wu ¹ Zhou Jianqing ¹ Bingyang Liu ^1*

• ¹ Ningbo Medical Centre Lihuili Hospital, Ningbo, China
• ² Hangzhou First People's Hospital, Hangzhou, Zhejiang Province, China

Background: Insulin 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.Methods: This 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.Results: Higher 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.Higher 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.