Background: Diabetic encephalopathy is a common complication of type 2 diabetes mellitus (T2DM) and a major cause of cognitive dysfunction. The kidneys and the brain share several similar physiological characteristics, which may render them susceptible to analogous pathological processes. Estimated glomerular filtration rate (eGFR) is a widely used indicator of kidney function and may reflect systemic microvascular injury, impaired renal function accelerates cerebral microangiopathy and exacerbates cognitive deterioration. Neuron-specific enolase (NSE) is a well-recognized neuronal injury biomarker, It is a glycolytic rate-limiting enzyme abundant in cerebral neuron cytoplasm, leaks into blood or cerebrospinal fluid upon neuronal membrane damage following central nervous system injury. Existing studies separately explored renal function or neuronal injury indicators in diabetic cognitive dysfunction, while few studies combined eGFR and NSE to jointly predict cognitive dysfunction in T2DM populations, lacking combined diagnostic evidence of kidney-brain damage markers.
Purpose: This study aimed to investigate the associations of eGFR and NSE with cognitive function in T2DM patients and evaluate their predictive value for cognitive dysfunction.
Methods: This cross-sectional study retrospectively enrolled 80 T2DM patients. Demographic, clinical, and laboratory data were collected. Serum NSE and eGFR were assessed. Cognitive function was evaluated using the Montreal Cognitive Assessment (MoCA). Patients were categorized into diabetic cognitive dysfunction group (DCD, MoCA < 26, n=40) and Diabetic non-cognitive dysfunction group (DNCD, MoCA >= 26, n=40) groups.
Results: Compared with the DNCD group, the DCD group had significantly lower eGFR and higher NSE, HbA1c, and Hcy levels (all P< 0.05). Pearson correlation analysis in the DNCD group demonstrated that eGFR was positively correlated with MoCA scores. In contrast, NSE, HbA1c and Hcy were all negatively correlated with MoCA scores (all P < 0.05). Multivariate regression further confirmed that NSE, glycated hemoglobin, and homocysteine were independently negatively associated with cognitive function, while eGFR was independently positively associated with cognitive function. ROC curve analysis revealed that both eGFR and NSE contribute to the diagnosis of cognitive dysfunction.
Conclusion: Elevated NSE, HbA1c, and Hcy are independently negatively associated with cognitive function, while eGFR was independently positively associated with cognitive function in T2DM patients. Combined detection of eGFR and NSE facilitates the early screening of diabetic cognitive dysfunction. This study compensates for the deficiency of single-organ biomarker research and provides provide a preliminary theoretical reference for future joint prediction model development.