Elevated blood urea nitrogen and creatinine ratio (BUNCr) is associated with decreased cognitive function and increased depressive symptoms, with depressive symptoms mediating part of the relationship between BUNCr and cognitive decline.
Highlights:
- BUNCr has a negative association with cognitive function, with higher BUNCr levels linked to lower cognitive performance.
- BUNCr is positively associated with depressive symptoms, meaning higher BUNCr levels correlate with more severe depressive symptoms.
- Depressive symptoms significantly mediate 7% of the relationship between BUNCr and cognitive function, indicating that part of the cognitive decline related to BUNCr can be attributed to increased depressive symptoms.
Source: BMC Psychiatry (2024)
Major Findings: Blood Urea Nitrogen (BUN) & Creatinine vs. Cognition & Depression (2024)
Feng et al. evaluated the relationships between Blood Urea Nitrogen (BUN) & Creatinine vs. cognition and depression in Chinese adults.
1. Elevated BUNCr & Cognitive Decline
The study found a negative association between the blood urea nitrogen and creatinine ratio (BUNCr) and cognitive function.
This means that higher levels of BUNCr are linked to poorer cognitive performance.
Cognitive function was measured using the Telephone Interview of Cognitive Status (TICS) scale.
Participants with higher BUNCr levels scored lower on cognitive tests, indicating a decline in abilities such as memory, orientation, and numerical reasoning.
The coefficient for this association was -0.192, with a 95% confidence interval (CI) of -0.326 to -0.059, suggesting a statistically significant relationship.
This finding implies that as BUNCr levels rise, cognitive abilities diminish, making it harder for individuals to perform everyday mental tasks effectively.
2. BUNCr & Depressive Symptoms
There is a positive relationship between BUNCr and depressive symptoms, indicating that higher BUNCr levels are associated with more severe depressive symptoms.
Depressive symptoms were assessed using the 10-item Center for Epidemiologic Studies Depression Scale (CES-D-10).
Participants with higher BUNCr levels exhibited more severe depressive symptoms, with a coefficient of 0.145 and a 95% CI of 0.006 to 0.285.
This finding suggests that individuals with elevated BUNCr are more likely to experience frequent feelings of sadness, hopelessness, and other symptoms associated with depression.
3. Depressive Symptoms as a Mediator
Depressive symptoms significantly mediate the relationship between BUNCr and cognitive function, accounting for 7% of the total effect.
The study employed causal mediation analysis to explore how depressive symptoms influence the relationship between BUNCr and cognitive function.
The total effect (TE) of BUNCr on cognition was -0.1992, while the direct effect (DE) was -0.1852, and the indirect effect (IE) through depressive symptoms was -0.014.
This indicates that part of the cognitive decline associated with higher BUNCr can be explained by the presence of depressive symptoms.
In other words, higher BUNCr levels not only directly affect cognitive function but also indirectly impair cognition by increasing depressive symptoms.
4. Consistency Across Models
The association between BUNCr, cognitive function, and depressive symptoms remained consistent across different statistical models and sensitivity analyses.
The study tested multiple linear regression models adjusting for various covariates such as age, sex, marital status, education, residence, alcohol consumption, smoking, BMI, hypertension, diabetes, and dyslipidemia.
Regardless of the adjustments, the negative association between BUNCr and cognitive function and the positive association between BUNCr and depressive symptoms remained significant.
This robustness across different models enhances the reliability of the findings.
5. Potential Mechanisms
Several potential mechanisms may explain the observed relationships, including changes in brain structure and function due to elevated BUNCr levels.
Elevated BUNCr may affect brain health by altering brain microstructures, causing brain shrinkage, and leading to abnormal brain activity.
These changes can contribute to cognitive decline.
Additionally, blood urea can disrupt long-term potentiation and synaptic function, leading to depressive symptoms.
The study suggests that understanding these mechanisms can help develop strategies to prevent cognitive decline and manage depressive symptoms in individuals with elevated BUNCr.
Study Overview: BUNCr vs. Cognition & Depression in Chinese Adults (2024)
The study evaluated the association between blood urea nitrogen and creatinine ratio (BUNCr) and cognitive function, as well as depressive symptoms, and to identify the mechanisms underlying these relationships.
Sample
Data were utilized from the China Health and Retirement Longitudinal Study (CHARLS) from 2015 to 2020, involving a final sample of 5,788 participants aged 45 and older.
Methods
- Cognitive Function Assessment: Measured using the Telephone Interview of Cognitive Status (TICS) scale.
- Depressive Symptoms Assessment: Measured using the 10-item Center for Epidemiologic Studies Depression Scale (CES-D-10).
- BUNCr Measurement: Calculated from blood samples taken and analyzed for blood urea nitrogen and creatinine levels.
- Statistical Analysis: Employed multivariate linear regression models to examine associations. Causal mediation analysis was used to identify the mediation effects of depressive symptoms between BUNCr and cognition.
- Covariates: Adjusted for demographic characteristics, behavioral traits, and health conditions.
Limitations
- Recall Bias: Reliance on participants’ recollection for some variables.
- Unmeasured Confounding: Despite adjustments, potential unmeasured confounding variables might bias the results.
- Incomplete Cognitive Evaluation: Cognitive function assessment might not cover all relevant aspects.
- Single Measurement of Biomarkers: Blood urea nitrogen and creatinine were measured only once, which may affect the precision of the findings.
Understanding BUNCr Levels, Cognitive Decline, & Depression
1. Primary Causality: Elevated BUNCr Leading to Cognitive Decline and Depression
The study primarily suggests that elevated blood urea nitrogen and creatinine ratio (BUNCr) levels lead to cognitive decline and depressive symptoms.
Here’s how this causality is understood:
- Kidney Function Impairment: Impaired kidney function results in the accumulation of uremic toxins like urea and creatinine in the blood. These toxins can cross the blood-brain barrier and exert neurotoxic effects, which can impair cognitive function and mood regulation.
- Neuroinflammation & Oxidative Stress: High BUNCr levels can induce chronic inflammation and oxidative stress, which damage brain cells and disrupt neural networks, leading to cognitive decline and depression.
- Altered Brain Metabolism: Elevated BUNCr levels disrupt brain metabolism and neurotransmitter balance, contributing to cognitive and mood disorders.
2. Reverse Causality: Cognitive Decline & Depression Affecting BUNCr Levels
While the primary focus of the study is on elevated BUNCr causing cognitive and mood issues, reverse causality is also a consideration:
- Behavioral Impact: Cognitive decline and depression can lead to poor dietary habits, reduced physical activity, and neglect of chronic conditions, all of which can further impair kidney function. Poor self-care can exacerbate kidney issues, leading to higher BUNCr levels.
- Medication & Treatment Compliance: Individuals with cognitive impairment or severe depression might not adhere to medication regimens or treatments that manage kidney function, potentially leading to elevated BUNCr levels.
3. Bidirectional Relationship
There is a possibility of a bidirectional relationship, where elevated BUNCr levels and cognitive decline/depression influence each other:
- Vicious Cycle: Impaired kidney function raises BUNCr levels, contributing to cognitive decline and depression. In turn, these mental health issues worsen kidney function through poor self-care, creating a feedback loop that perpetuates both conditions.
4. Confounding Variables: Independent Factors Affecting Both BUNCr Levels & Mental Health
Other variables might independently influence both BUNCr levels and the risk of cognitive decline and depression:
- Chronic Health Conditions: Diseases such as diabetes, hypertension, and cardiovascular diseases can impair kidney function and also contribute to cognitive decline and depression.
- Socioeconomic Status & Lifestyle Factors: Low socioeconomic status, poor diet, lack of exercise, and limited access to healthcare can simultaneously affect kidney health and mental health.
- Age & Genetic Predisposition: Aging naturally leads to declining kidney function and cognitive abilities. Genetic factors can predispose individuals to both kidney disease and mental health issues.
Conclusion: BUN & Creatinine vs. Cognition & Depression
This study highlights a significant association between elevated blood urea nitrogen and creatinine ratio (BUNCr) and both cognitive decline and depressive symptoms in a middle-aged and elderly Chinese population.
The findings suggest that impaired kidney function and related metabolic imbalances may play a crucial role in deteriorating brain health and mood regulation.
Elevated BUNCr levels, influenced by factors such as chronic kidney disease, dehydration, high protein intake, and age-related health decline, are linked to worse cognitive performance and higher depressive symptoms.
Understanding these associations provides valuable insights into the prevention and management of cognitive impairments and depression, emphasizing the importance of monitoring kidney function and addressing underlying health conditions to promote better cognitive and mental health outcomes.
References
