Blood and imaging biomarkers of blood-brain barrier disruption in diabetic individuals with cognitive impairment

BACKGROUND: Blood-brain barrier (BBB) disruption is a recognized contributor to neurodegenerative diseases. However, its specific role in cognitive decline in diabetes has not been sufficiently explored. AIMS: This study aimed to evaluate the association between BBB integrity and cognitive function and to investigate the discriminative ability of BBB-related biomarkers for cognitive impairment in individuals with type 2 diabetes mellitus (T2DM). METHODS: In this case-control study, participants were recruited from the Second Affiliated Hospital of Nanchang University. All subjects underwent dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI). We compared quantitative brain imaging (Ktrans and Ve) and serum platelet-derived growth factor receptor β (PDGFRβ) between diabetic individuals with and without cognitive impairment. The relationships between these biomarkers and cognitive performance were assessed using linear regression analyses. The discriminative capacity of each biomarker for distinguishing groups was evaluated using receiver operating characteristic (ROC) curve analysis. RESULTS: T2DM individuals with cognitive impairment exhibited significantly elevated Ktrans and Ve levels compared to those without, which correlated inversely with MoCA scores in key brain regions. Serum PDGFRβ was also independently associated with impaired cognition. Every biomarker individually demonstrated high discriminative power for evaluating cognitive status, with AUC values of 0.908 (95% CI: 0.842 to 0.973) for Ktrans, 0.923 (95% CI: 0.86 to 0.986) for Ve, and 0.839 (95% CI: 0.751 to 0.928) for PDGFRβ. CONCLUSIONS: Our results confirm the critical role of BBB dysfunction in diabetic cognitive impairment. The biomarkers serum PDGFRβ, Ktrans, and Ve showed potential associations with this condition, suggesting their clinical value for future clinical application in risk stratification and therapeutic monitoring in T2DM population. TRN: ChiCTR2400085417, 2024.06.06, retrospectively registered.