The global aging phenomenon poses unprecedented challenges, notably in aggravating concerns associated with cognitive impairment (1–5). Cognitive impairment encompasses the reception and processing of information, characterized by memory loss, diminished understanding, impaired focus, and difficulties in calculation (6, 7). These cognitive alterations are regarded as the preclinical phase of dementia, possibly affected by factors like fasting glucose levels, physical performance, and other variables, highlighting its significance as a major public health concern (3, 8–10). Therefore, identifying risk factors to prevent cognitive impairment at early stages is essential (3, 6, 11–13).

There is growing evidence supporting the association between insulin resistance (IR) and the risk of cognitive decline (14–17). However, previous studies have primarily relied on the gold standard methods of insulin clamp and intravenous glucose tolerance test for diagnosing IR, which are not commonly performed in clinical settings (18–20).

The triglyceride-glucose (TyG) index, a readily available and cost-effective metric derived from triglyceride (TG) and fasting blood glucose (FBG) levels, has been recognized as a promising surrogate marker for IR (14, 18, 19, 21). Extensive epidemiological research has indicated significant links between the TyG index and various diseases, including cardiovascular diseases, cancers, and diabetes (22, 23). Nonetheless, the validity of the TyG index as an alternative indicator of IR in assessing its relationship with cognitive impairment is still in question. Prior investigations have largely concentrated on the TyG and cognitive function relationship within specific demographics, such as non-diabetic, gender-specific cohorts, or individuals living in rural areas, often focusing on specific cognitive domains (24–27).

This study, grounded in population-based research, seeks to explore the relationship between the TyG index and the occurrence of cognitive impairment in a wider elderly population. Utilizing the most recent cognitive function follow-up data from the 2020 China Health and Retirement Longitudinal Study (CHARLS) database, our work aims to offer an exhaustive and prolonged examination of this association across the entire elderly cohort. The study hypothesis is that elevated TyG index may be associated with cognitive impairment among older adults in China.

In this study, we observed a significant association between a higher TyG index and cognitive impairment in older adults (aged 65 years and above). A follow-up visit in 2020 revealed a gradual decline in cognitive function scores compared to the baseline in 2015. Stratified analysis by age, gender, BMI, chronic diseases, and diabetes showed that individuals with a higher TyG index faced a greater risk of cognitive impairment, with the exception of those with lower BMI, those without chronic diseases, and males. These findings suggest that a higher TyG index could be a potential risk factor for cognitive impairment in older adults, particularly in females and in those with higher BMI and chronic diseases.

The aging global population presents an unprecedented challenge, raising significant concerns (1–3). The rapid pace of aging intensifies the challenges associated with cognitive impairment (4, 5). The age-related decline in cognitive function has become a significant public health issue, leading to adverse health outcomes (11, 13). Cognitive impairment often manifests years before the onset of dementia, underscoring the need to explore its mechanisms and to implement preventive measures aimed at risk factors. Previous research has identified several key factors contributing to cognitive decline, including genetic predisposition, cardiovascular disease, and exposure to air pollution (36–40).

IR is characterized by reduced sensitivity and responsiveness to the effects of insulin, acting as a central factor in the emergence of various health issues, such as diabetes, cardiovascular diseases, and cognitive decline (3, 14). Moreover, some evidence suggests that IR is linked to an increased risk of cognitive decline (14–16). The hyperinsulinemic euglycemic clamp, despite its exceptional sensitivity in assessing the body’s response to insulin, is costly and complex, limiting its use in clinical environments. The homeostasis model assessment of insulin resistance (HOMA-IR), based on FPG and insulin measurements, is considered the gold standard for evaluating insulin sensitivity. However, the measurement of insulin levels is not commonly included in routine clinical practice, thereby restricting the use of HOMA-IR in such contexts. The TyG index, a practical measure of IR derived from TG and FBG levels, offers a cost-effective and accessible alternative for IR assessment, gaining widespread adoption in research (14, 18, 19). Epidemiological studies have linked the TyG index to various conditions, including cardiovascular diseases, cancers, and diabetes. Yet, the effectiveness of the TyG index as an indirect marker for IR in exploring its association with cognitive impairment remains to be fully ascertained.

Previous research on the TyG index and cognitive function has predominantly focused on specific demographic groups, such as non-diabetic individuals, gender-specific populations, and rural dwellers, often categorizing cognitive function into distinct domains (24–27). Utilizing data from the National Health and Nutrition Examination Survey (NHANES), Wei et al. found a notable correlation between a high TyG index and reduced cognitive function, as determined by the CERAD test, in non-diabetic elderly individuals in the United States (24). Similarly, a study among elderly residents in rural China linked elevated TyG index values with diminished cognitive performance and brain atrophy (25).

Our population-based study aimed to explore the relationship between the TyG index and cognitive impairment among the elderly population in China. Utilizing data from a continuous cohort, we collected information from consecutive cognitive assessments conducted in 2020. We found a significant association between a higher TyG index and cognitive impairment in older adults during the follow-up visits in 2020, especially pronounced in females, individuals with a higher BMI, and those suffering from chronic conditions. Additionally, our findings showed that cognitive function scores were lower in females than in males. These results align with previous research. Earlier investigations have consistently indicated that females are at a greater risk of cognitive impairments compared to males (3, 41, 42). A study examining a 5-year change in the TyG index and its impact on cognitive function found that females in the second quartile of longitudinal TyG index change exhibited a significant association with reduced cognitive performance as measured by the CERAD test (26). Moreover, it was noted that females have a higher vulnerability to cognitive impairment compared to males (3).

Several factors might elucidate the observed results, necessitating consideration of the underlying mechanisms. Insulin possesses the ability to traverse the blood-brain barrier through specific receptors, affecting both behavioral and metabolic functions (17, 43). IR represents a unique metabolic disorder often characterized by increased insulin levels, which can lead to neurodegeneration and persistent memory impairments due to prolonged exposure of brain neurons to elevated insulin levels (44). Furthermore, IR could diminish cerebral glucose metabolism in particular brain regions, possibly adversely affecting memory function in individuals (45). Some clinical studies have indicated that TG can cross the blood-brain barrier, potentially impairing cognitive function by inducing insulin receptor resistance (46). In our study, most female participants were postmenopausal, a phase associated with reduced estrogen levels. Previous research has identified estrogen as vital for learning and memory, providing neuroprotection and potentially enhancing cognitive function through estrogen therapy (47, 48). This could explain the more pronounced cognitive decline observed in females compared to males in our study. In the BMI-stratified analysis, the link between an elevated TyG index and cognitive impairment was observed solely in overweight and obese individuals, highlighting IR’s traditional association with obesity, which is closely related to brain atrophy (25). Additionally, a study examining the relationship between the TyG index and lower brain volume found this association exclusively in individuals with a BMI ≥24 kg/m² (25).

The issue of cognitive impairment is becoming increasingly evident as the population ages. Serving as an early indicator of dementia, cognitive impairment is associated with a notably adverse prognosis, affecting individual quality of life and placing burdens on families and society. The early prevention of cognitive impairment is thus critical and urgent. Our research suggests that the TyG index could serve as an alternative marker of IR for predicting cognitive impairment in individuals over 65 years old in China, with a significant relationship observed between high TyG index and cognitive impairment. Targeted interventions could help in mitigating cognitive impairment, potentially decreasing the incidence of dementia. Additionally, further exploration into identifying more predictive risk factors for cognitive impairment is necessary to achieve the objective of early prevention.

This study has several limitations. First, it is important to recognize that the study was observational. Despite efforts to adjust for known confounders, the potential impact of unmeasured confounders on the outcomes cannot be disregarded. Therefore, the applicability of our findings may be somewhat restricted. Moreover, we evaluate cognitive function using episodic memory and mental acuity rather than clinical diagnosis. Comprehensive assessment across multiple dimensions is crucial for understanding overall cognitive function, highlighting limitations when evaluating solely based on episodic memory and mental acuity. However, these neuropsychological tests are widely regarded as reliable screening tools for measuring cognitive function and are extensively used in clinical practice (49). Finally, due to data availability limitations, our analysis was confined to a 5-year follow-up period from 2015 to 2020. Future studies should consider employing repeated-measures designs over longer durations and examining more potential pathways. Subsequent research is warranted to refine these findings further.

The results of this study reveal a notable association between elevated TyG index levels and the occurrence of cognitive impairment among the elderly Chinese demographic. The initiation of targeted intervention strategies may effectively mitigate cognitive impairment, potentially decreasing the prevalence of dementia.

The datasets presented in this study can be found in online repositories. The names of the repository/repositories and accession number(s) can be found below: http://charls.pku.edu.cn/pages/data/111/zhcn.html.

The studies involving humans were approved by the Ethical Review Committee of Peking University (IRB00001052-11015). The studies were conducted in accordance with the local legislation and institutional requirements. Written informed consent for participation was not required from the participants or the participants’ legal guardians/next of kin in accordance with the national legislation and institutional requirements.

WMB: Data curation, Formal analysis, Investigation, Methodology, Validation, Writing – original draft. SA: Data curation, Investigation, Project administration, Validation, Writing – original draft. HJ: Data curation, Formal analysis, Investigation, Project administration, Software, Writing – original draft. JX: Conceptualization, Formal analysis, Methodology, Resources, Supervision, Writing – review & editing. LJQ: Data curation, Formal analysis, Investigation, Methodology, Resources, Supervision, Writing – review & editing.