With the advent of global aging, the rising incidence of cognitive function impairment and dementia will become a major public health concern for humanity (1). Projections suggest that by 2050, estimated 152 million people worldwide will be living with cognitive function impairment (2). The disease severely affects the quality of life for patients, as well as imposing a heavy socio-economic burden.

Given the irreversible nature, exploring modifiable lifestyle and risk factors is essential in the endeavor to delay and prevent cognitive function impairment (3). Diet stands out as a modifiable determinant worthy of investigation. Studies indicate that adherence to a higher-quality diet, consistent with the Dietary Guidelines for Americans (DGA), is related to better cognitive performance among the aging population in the United States (4).

Despite extensive research into cognitive function impairment, its etiology, pathogenesis and treatment remain incompletely understood. Previous investigations have suggested that inflammation, oxidative stress, metabolic abnormalities may be involved in the development of cognitive function impairment (5, 6). The brain is particularly vulnerable to oxidative stress due to its distinctive structure, such as its high oxygen utilization, rich unsaturated fatty acid composition, and relatively low antioxidant capacity (7). Research indicates that regular consumption of antioxidants in the diet can enhance antioxidant defense mechanisms and mitigate oxidative stress by elevating plasma antioxidant concentrations. Studies have shown that daily dietary consumption of antioxidants can enhance antioxidant defense and weaken oxidative stress elevating antioxidant level in the blood (8). Modifying dietary patterns may thus serve as an effective strategy to alleviate cognitive function impairment by reducing systemic oxidative stress levels.

The Composite Dietary Antioxidant Index (CDAI) is an effective and reliable nutritional tool for assessing the overall antioxidant properties of an individual’s diet (9). It is a composite score summarizing multiple dietary antioxidants, including vitamins A, C, and E, carotenoids, selenium, and zinc (10, 11). CDAI is a composite index, and previous studies have generally been limited to examining the relationship between specific antioxidants and cognitive performance, but there has been limited research on the potential combined benefits of antioxidants on cognitive impairment. Therefore, we analyzed data from the National Health and Nutrition Examination Survey (NHANES) to investigate potential correlations between the CDAI and cognitive function impairment, with the goal of decreasing the incidence of cognitive function impairment through dietary interventions.

Aging is a physiological process accompanied by the decline of physical and cognitive functions, the decline of cognitive function affects memory, attention, spatial learning, executive function, and may eventually progress to cognitive dysfunction or even dementia (24). Cognitive function impairment is common in the aging process. Understanding the connection between diet and cognitive abilities is critical for the prevention and management of cognitive function impairment (25). This cross-sectional study examined the association between CDAI and cognitive impairment in older adults in the United States. We observed a significant positive association between higher CDAI scores and cognitive function, suggesting that CDAI is a protective factor against the development of cognitive impairment and that antioxidant diets may reduce the risk of cognitive impairment. In multivariate logistic regression models adjusted for confounding variables, the relationship between higher CDAI scores and cognitive function CERAD test results was robust. Further, RCS curves showed an L-shaped nonlinear correlation between the CDAI index and cognitive performance.

Here, the results of the three different cognitive function tests were slightly different. After adjusting various covariates, the correlation between CDAI score and CERAD word learning subtest was still significant, while the correlation between CDAI score and AFT and DSST was not statistically significant, indicating that CDAI may have a significant effect on improving memory ability, but not in processing speed, sustained attention and executive function. Episodic memory impairment is a hallmark of dementia and serves as a critical diagnostic criterion for typical Alzheimer’s disease. Early detection of memory function impairment is pivotal for identifying high-risk populations at a preclinical stage of dementia. Furthermore, timely and proactive interventions targeting memory function can effectively enhance cognitive outcomes in elderly individuals. The CERAD Word Learning Subtest and the Word Delayed Recall Test comprehensively assess both immediate and delayed recall abilities, providing a measure of memory performance. CERAD scores are widely recognized as a reliable reflection of memory function. In our study, the observed correlation between the CDAI and CERAD outcomes was notably significant. This finding underscores the unique relevance and precision of CDAI as an indicator. It highlights its potential value in identifying dietary patterns associated with memory function and cognitive health.

Subgroup analyses revealed that more significant effects were observed in women, high school education and above, married or non-Hispanic White individuals with higher CDAI scores, suggesting that these subgroups may derive greater benefits from higher dietary antioxidant intake. Gender differences may be due to hormonal and metabolic pathways. Individuals with higher education levels likely possess greater health literacy. This enables them to make more informed dietary choices aligned with the principles of the CDAI. Additionally, marriage often provides a support system that encourages healthier lifestyle choices, including diet. Married individuals may benefit from shared meal preparation, which increases the likelihood of consuming balanced and nutritious meals. For non-Hispanic White individuals, cultural dietary habits and genetic differences in antioxidant metabolism may explain their greater benefit from higher CDAI scores.

In recent years, the relationship between cognitive performance and dietary patterns has garnered significant attention (26). Nutrients from food can influence immune responses and modulate neuroinflammatory processes involved in the pathogenesis of dementia and cognitive impairment (27). Specific dietary patterns, such as the Mediterranean and MIND diets, emphasize antioxidant-rich foods and have been linked to slower cognitive decline and reduced risk of Alzheimer’s disease. These patterns support the notion that long-term antioxidant intake contributes to cognitive resilience and aligns with the principles underlying the CDAI (28, 29). This underscores the potential of dietary antioxidants in preventing age-related conditions such as cardiovascular diseases (30), cancers (31) and neurodegenerative diseases. Essential dietary antioxidants, including β-carotene (32), vitamins C and E (33), selenium, zinc, manganese, and coenzyme Q10 (34), are crucial in countering the adverse effects of oxidative stress. Supplementation with antioxidants can help restore depleted endogenous antioxidant levels, thereby ultimately reducing oxidative damage.

Oxidative stress refers to the excessive production of highly active molecules in the body, such as reactive oxygen free radicals (ROS) and reactive nitrogen free radicals (RNS), the oxidation production exceeds the removal of oxides, resulting in tissue damage (33, 34). During brain aging, neurons and microglia accelerate apoptosis, mitochondrial dysfunction, release more ROS and RNS, metabolize into superoxides and hydroxyl radicals, induce increased activity of REDOX signaling cascade, resulting in impaired synaptic function, and further increase oxidative stress and oxidative damage (35). With the increase of age, the number of antioxidative enzymes decreases, which is a key component of the body’s antioxidative defense mechanism, and individuals’ adaptability to oxidative stress declines accordingly. The hippocampus, a critical brain region responsible for learning and memory, is particularly susceptible to oxidative stress. Due to the high metabolic activity and sensitivity of hippocampal neurons to oxidative damage, excessive ROS and RNS tend to accumulate in this area. Oxidative stress in the hippocampus leads to mitochondrial dysfunction, DNA damage, and protein oxidation, ultimately impairing neuronal survival and synaptic plasticity.

Antioxidant food sources are vital for patients with cognitive impairments, particularly in protecting the hippocampus. Dietary antioxidants reduce oxidative stress through bioactive molecules, regulate gene expression, and modulate cellular signaling pathways. For example, selenium protects hippocampal neurons by activating glutathione peroxidase and thioredoxin reductase, preventing lipid peroxidation, and maintaining neuronal membrane integrity. Zinc is an essential component of zinc-dependent antioxidant enzymes in the hippocampus and is crucial for glutamatergic synaptic transmission and synaptic stability (36). The metabolite of vitamin A, retinoic acid (RA), supports hippocampal synaptic plasticity and alleviates age-related cognitive decline. Further analysis of the correlation between CDAI components and CERAD (memory) revealed that carotenoids and vitamin E contribute the most to the antioxidant effects of CDAI. Non-enzymatic antioxidant vitamin E effectively reduces oxidative stress (8), while carotenoids exhibit potent antioxidant properties by neutralizing reactive oxygen species (ROS) and regulating inflammation, thereby significantly protecting hippocampal neurons. Thus, dietary intake of antioxidant-rich nutrients holds promise in preventing and mitigating cognitive impairment caused by oxidative stress. However, the precise molecular mechanisms warrant further investigation.

Balanced nutrient intake contributes to overall health during the aging process, and excessive intake of single nutrients is detrimental to both cognitive function and health. Moreover, the intake of single antioxidants cannot counteract the oxidative stress under pathological conditions and might even interfere with the body’s redox balance. Therefore, the CDAI index was introduced in this study. The CDAI serves as a quantitative measure to assess the aggregate antioxidant capacity associated with specific dietary intake, utilized across diverse research investigations. Evidence suggests that increased CDAI scores are associated with a lowered susceptibility to age-related diseases such as cardiovascular disease and cancers (37, 38). Our study provides additional evidence that CDAI scores are associated with lower cognition. Regardless of other significant covariates, this association remains consistent and meaningful. Higher CDAI scores showed a protective effect in cognitive assessments, suggesting that CDAI scores play a prominent role in immediate and delayed learning abilities in the elderly when acquiring new linguistic information. Specific mechanisms require further investigation. For clinicians, CDAI can help identify deficiencies in antioxidant intake, thereby guiding personalized dietary interventions focused on improving CDAI scores and promoting cognitive performance. It can also be used to track changes in diet quality and evaluate the effectiveness of dietary adjustments. However, the composite nature of CDAI may make direct dietary recommendations more challenging. To address this, clinicians can prioritize recommending antioxidant-rich, nutrient-dense foods and supplements to help individuals optimize their dietary structure and health outcomes. In public health, priority should focus on high-risk populations, such as older adults and those with low antioxidant intake. Early screening tools are essential to identify individuals at risk of cognitive impairment, enabling targeted dietary education and continuous monitoring. CDAI offers a practical and evidence-based approach for assessing dietary antioxidant intake and evaluating interventions, particularly at the regional level. Public health initiatives can use CDAI to design targeted campaigns promoting antioxidant-rich foods. Incorporating a lifelong cognitive health framework into national dietary guidelines is crucial. This approach promotes antioxidant-rich dietary patterns early in life to prevent cognitive decline, addressing the challenges of an aging population.

Nomograms provide an effective way to communicate multifactorial predictions in a straightforward and accessible manner. In this study, the nomogram model could be used to predict the risk of cognitive impairment and even dementia, which will help clinicians to better identify high-risk groups of cognitive impairment. Adding more predictors could improve the nomogram’s performance, we have incorporated additional variables, such as physical activity, depression and comorbidities, into the model and reassessed its performance. Considering the model’s sensitivity and the AUC, it is more suitable as a supplementary tool rather than a standalone diagnostic method. Integrating the model into a multi-modal diagnostic framework is also an option to enhance its practical utility. Certainly, future studies are necessary to validate the model in external populations to enhance its generalizability and ensure its clinical applicability.

To enhance the nomogram model’s utility and accuracy, future research should integrate biomarkers like oxidative stress and neuroinflammatory markers to strengthen its biological foundation and insights into cognitive decline. Longitudinal data validation is crucial to confirm its predictive stability across diverse populations. Additionally, machine learning techniques can improve the model by analyzing complex datasets, identifying novel predictors, and dynamically adapting to different cohorts.

This study demonstrated an association between CDAI scores and cognitive function within a nationally representative sample of individuals over 60 years in the United States. Although similar studies have investigated the relationship between dietary antioxidants and cognitive outcomes (39), our study offers several important distinctions. First, the CDAI in our study was constructed using a different combination of antioxidant nutrients, including carotenoids instead of manganese. Second, we emphasized domain-specific cognitive outcomes and found a particularly strong association between CDAI and memory performance, which is crucial for early dementia detection. Most importantly, we developed and validated a nomogram prediction model, enhancing the clinical applicability of our findings. These contributions, built upon shared data sources but employing distinct variable definitions, analytical approaches, and clinical perspectives, underscore the novelty and added value of our research.

However, certain limitations must be acknowledged. First, this study was a cross-sectional analysis, we cannot determine the causal relationship between CDAI scores and cognitive performance. Second, the 24-h dietary recall interview is questionnaire-based, so dietary assessments may involve measurement error and inaccuracies. Lastly, we excluded participants with missing information, and we could not determine whether these individuals affected the results. We emphasize the need for prospective cohort studies to track dietary interventions and their impact on cognitive changes over time. Furthermore, randomized controlled trials are essential to assess the effects of antioxidant supplementation or specific dietary strategies on cognitive decline.

In conclusion, there is a significant negative association between CDAI and low cognition in the U.S. elderly population, with higher CDAI scores having a protective effect on cognitive function. A nomogram was constructed to predict the risk of cognitive impairment, which will help clinicians to better identify high-risk groups of cognitive impairment. This study provides a new way to explore dietary intervention for cognitive function impairment.