Mild cognitive impairment (MCI) is an intermediate state between normal aging and dementia, such as Alzheimer’s disease (AD), and is characterized by a loss of memory and a decline in learning and cognitive function (1). Studies have shown that several years before the onset of AD, metabolic abnormality can be observed in blood biochemical markers related to the disease (2), such as increased blood β-amyloid (Aβ), tau, and neurofilament light chain (NfL) levels. In vivo studies also reported the signals and substances that communicate between the liver and brain through the nervous and circulatory systems; thereby, the concept of the ‘liver-brain axis’ was raised accordingly (3). Data from numerous animal experiments have explored the linkage of liver function with cognition from the biological perspective (4, 5), further demonstrating the impact of the liver-brain axis on cognitive function, including alteration of the blood–brain barrier (BBB) structure (6), generation of toxic metabolites (7, 8), and disruption in normal Aβ metabolism (5).

Various prediction models have been proposed to evaluate liver function, such as the fatty liver index (FLI) (9), hepatic steatosis index (HSI) (10), AST/HDL-C and ALT/HDL-C (11), and elevation of these indicators may partially indicate a decline in liver function. Moreover, the relation between damaged liver function and cognitive impairment has also been established in a population-based study (12–14). Therefore, improving cognition by enhancing liver function may represent a novel strategy for preventing cognitive dysfunction in the elderly.

The American Heart Association recommends adopting a healthy lifestyle and balanced dietary pattern to promote overall health (15). Smoking (16) and alcohol consumption (17) are well-established risk factors for numerous chronic diseases. In contrast, several studies have shown that tea consumption (18, 19) and regular physical activity (20, 21) benefit both liver and cognitive functions. Studies have found that older adults who remain physically active tend to preserve cognitive abilities for a longer period compared with their sedentary counterparts (22). Moreover, sleep disorders and insufficient sleep duration have been identified as important risk factors for both neurocognitive decline and liver disease (21, 23). Collectively, these findings suggest that a healthy lifestyle—including non-smoking, moderate alcohol use, regular physical activity, and adequate sleep—plays a pivotal role in maintaining liver and brain health. Moreover, adherence to balanced dietary patterns is equally critical for promoting overall health. In addition to a healthy lifestyle, the role of balanced dietary patterns in promoting body health has been extensively reported. The Chinese Food Guide Pagoda, developed based on the Dietary Guidelines for Chinese Residents, also encourages Chinese residents to consume diverse food items to ensure adequate nutrient intake and mitigate the risk of chronic diseases (24).

Many studies have explored the relationship between a single lifestyle, dietary intake, and liver function with cognitive function in the elderly, respectively. However, the combined impacts of lifestyle and dietary patterns on liver and cognitive functions remain unclear. This cross-sectional study was designed to examine how lifestyle and dietary patterns affect liver and cognitive functions in the elderly and whether there are synergistic effects. In addition, given the increasing recognition of liver function indicators as potential biomarkers, it is important to explore their predictive ability for mild cognitive impairment. Therefore, this study also aimed to evaluate whether liver function indicators could predict the risk of MCI by applying receiver operating characteristic (ROC) curve analysis.

In this study, we constructed a HLS and a HDS based on an individual’s lifestyle and dietary pattern to comprehensively assess their individual effects on liver and brain function. We found that HLS was significantly negatively correlated with AST/HDL-C and ZJU, whereas no significant correlation was observed for HDS with these indicators. Notably, among these liver function indicators, only AST/HDL-C was significantly associated with MCI risk, while ZJU showed no significant association with cognitive outcomes. According to the 2021 Scientific Research Report on dietary guidelines for Chinese residents, the diet quality of most Chinese residents remains suboptimal. Notably, the median HDS for this population was only ‘1’ in this study, indicating that the per capita dietary intake was substantially below the recommendations of the Chinese Food Guide Pagoda (2022). Similarly, Chao et al. found that unbalanced dietary patterns significantly increase the risk of abnormal liver function (33). Thus, low HDS (MedianHDS = 1) could explain why this research’s correlation between diet and liver function was insignificant. However, liver function can be significantly improved through a healthy lifestyle, including abstaining from smoking and alcohol (25), drinking tea (27), performing housework, and engaging in physical activity (29).

We also explore the relationship between lifestyle and diet intake with liver and brain function. Patients with MCI had lower MoCA scores and shorter education duration. These findings are consistent with previous studies (34), suggesting the protective effect of good education on cognition. Regarding lifestyle, we observed that MCI patients were more likely to have drinking tea habits. The observed increased percentage of subjects with tea-drinking habits in MCI patients might be attributable to the health education of MCI patients for managing their lifestyle (27, 28). Although Sun et al. reported that excessive tea consumption could increase brain burden and might cause potential damage to brain function (35), most of the published documents emphasized the protective effect of moderate tea consumption on overall health status and the prevention of chronic diseases (27, 28), among them, Hu’s study based on the data of UK Biobank (36), found that consuming approximately three cups of tea per day (about 250 mL per cup, totaling ~750 mL/day) was associated with the greatest reduction in Alzheimer’s disease risk. In addition, we found that the subjects from the control group showed a greater preference for reading and housework. As a mental activity, reading was proved to significantly enhance cognitive function (37), while housework, as a form of moderate physical activity, was also found to influence cognition positively (29). Regarding liver function, we found that the MCI patients exhibited higher plasma AST/HDL-C ratios than the controls. This data further demonstrated the potential correlation between poorer liver function and the increased risk of cognitive impairment (4, 5).

We examined the relation between HDS, HLS, MoCA scores, and liver function indicators (AST/HDL-C, ALT/HDL-C, HSI, and ZJU). Our data demonstrated a significantly positive correlation between HDS and MoCA scores. Balance diets may alleviate cognitive impairment by promoting the hippocampus’s structural and functional plasticity and upregulating neurotrophic factors’ expression (38). These results suggest that a balanced dietary pattern may be critical in enhancing brain function. Zhang et al. found that brain regions were more sensitive to N-3 PUFA in diet than the liver (39). This conclusion also explains why diet might influence brain function more than liver function through the beneficial components of certain diets.

Interestingly, we observed a significant negative correlation between HLS and liver function indicators in the MCI population (Figure 2). This suggests that individuals with MCI may experience more significant improvements in liver function through adopting a healthy lifestyle. Whereas in the control group, a significant negative correlation was found between liver function indicators and cognitive scores. Aligning with the existing studies, Gao et al. advocated that early intervention in unhealthy livers could help prevent dementia (14). These data highlight the close association between impaired liver and cognitive decline. Furthermore, significant positive correlations among the four liver function indexes were also observed in our study, indicating their consistent and collective ability to reflect liver function.

We further analyzed the relation between HDS, HLS, liver function, and the risk of MCI. We did not observe a statistically significant association between HDS and the risk of MCI. However, adhering to a healthy lifestyle significantly reduces the risk of MCI. Regarding the relationship between liver function and cognition, after adjusting for confounders, elevated plasma AST/HDL-C and ALT/HDL-C ratios were associated with an increased risk of MCI. Previous studies have suggested that lower levels of liver enzyme ALT are linked to the increased brain Aβ protein deposition (40), while plasma HDL-C acts as a carrier of Aβ in the circulatory system to facilitate its metabolism (41). A decline in circulating HDL-C level may impair the body’s ability to clear circulatory Aβ. Thus, combining liver enzymes (AST and ALT) with plasma HDL-C provides better predictive capacity for MCI, likely reflecting their role in in vivo Aβ metabolism. This finding may also explain why HSI and ZJU, which are predictors of live function, did not show significant associations with the risk of MCI. Notably, the predictive power of AST/HDL-C and ALT/HDL-C for MCI underscores the connection between impaired liver function and cognitive decline. These results demonstrated the potential role of liver function-related markers in identifying individuals’ risk for MCI.

The results of RCS indicated that plasma AST/HDL-C and ALT/HDL-C ratios were positively associated with the risk of MCI, with cut-off values of 14.1 and 10.1, respectively. Prior studies have reported that the plasma AST/HDL-C and ALT/HDL-C ratio thresholds at 14.37 and 15.97 could be used to predict the damage status of liver function (11). As the most significant peripheral organ responsible for the clearance of Aβ, the liver plays a critical role in Aβ metabolism (42). The observed lower predictive thresholds for MCI than for hepatic dysfunction suggest that declining liver function may begin to impair cognition by reducing Aβ clearance even before liver function damage. Therefore, these data indicated the potential importance of maintaining normal liver function in inhibiting the pathology progress of cognitive decline.

This study examined the relationship between liver function, healthy lifestyle, dietary patterns, and cognitive function. Using the HLS and HDS, we comprehensively assessed participants’ lifestyles and dietary patterns. As expected, poor liver function was significantly associated with an increased risk of MCI. These findings highlight the importance of integrating lifestyle, dietary, and liver function considerations when interpreting cognitive outcomes in older adults. A healthy lifestyle and balanced diet demonstrated protective effects on both liver and cognitive functions, suggesting that interventions targeting these areas may help mitigate the risk of cognitive decline. Thus, beyond their individual effects, maintaining normal liver function alongside healthy lifestyle and diet patterns may be crucial in supporting cognitive health in the elderly.

The strength of our study is that, compared with conventional enzyme-based liver function evaluating indicators (such as AST, ALT, and GGT), the present study combined enzyme-based (AST and ALT) with non-enzyme-based parameter (HDL-C) to comprehensively evaluate individual’s liver function, which could more accurately reflect individual’s liver function status. This study has several limitations. Firstly, due to the cross-sectional nature of the data, we are unable to monitor dynamic changes in lifestyle, dietary patterns, liver function, and cognitive ability over time, which limits causal inference and the assessment of temporal relationships. Future research should employ longitudinal studies to address these gaps. Secondly, our data indicated that liver function might mediate the association between HLS, HDS, and cognition. The cross-sectional study design of the present study could not provide much more convincing proof. Thirdly, it should be noted that cognitive data of 630 participants were used for analyses. As a result, the sample size differed between analyses focusing on diet, lifestyle, and liver function and those including cognitive outcomes. This discrepancy reflects the use of the largest available dataset for each research focus rather than a comparison of different groups. Nevertheless, the exclusion of participants without cognitive assessments may introduce selection bias, and the generalizability of our findings regarding cognition should therefore be interpreted with caution. Therefore, a population-based cohort or interventional study is needed to further explore the underlying mechanisms.

Despite these limitations, our findings provide several practical implications for healthcare professionals and public health strategies. First, mental and physical activities, such as regular reading and engaging in housework, could be promoted as feasible lifestyle strategies to enhance cognitive resilience in older adults. Second, monitoring liver function markers such as the AST/HDL-C ratio may help identify individuals at elevated risk of cognitive decline, enabling earlier preventive interventions. Together, these recommendations highlight potential avenues for community-based programs aiming to reduce the burden of cognitive impairment.

Collectively, our findings indicated a strong association between liver and cognitive function, and AST/HDL-C could be a potential liver function-based parameter to predict the cognitive status of the elderly. Poor liver function correlates significantly with cognitive impairment, suggesting normal liver function is beneficial for the elderly to prevent cognitive function decline. Additionally, a healthy lifestyle and rationale dietary pattern might improve liver and brain function.