Gray matter reserve modulates the association between glymphatic system function and cognition in patients with T2DM

Introduction: We aims to explore the relationship between the glymphatic function and cognitive function in patients with T2DM and whether this relationship is modulated by gray matter (GM) integrity. Methods: In total, 65 patients with T2DM and 65 healthy controls (HCs) were recruited. All participants underwent evaluation using a comprehensive cognitive assessment scale. The ALPS index was calculated based on DTI data, and the disparity in ALPS index values between groups was examined. The voxel-based morphometry method was used to perform GM volume analysis. Multiple linear regression analysis was conducted to identify the GM regions associated with the ALPS index. The interactions among the ALPS index, GM volume and cognition were explored. Results: The ALPS index in patients with T2DM was significantly lower than that in HCs. In addition, our analysis revealed a correlation between the ALPS index and GM volume in the insular region, and this region was consistent with the GM atrophy region observed in the patient cohort. Moreover, a significant negative correlation was observed between the ALPS index in patients and performance on the Trail Making Test Part-A, and this relationship was moderated by GM integrity. Conclusion: A decreased ALPS index was found in T2DM patients, indicating impaired glymphatic function in this population. Furthermore, the association between the ALPS index and cognitive performance in T2DM patients was influenced by GMV in insula. Therefore, the ALPS index has the potential to be used as a biomarker of cognitive impairment in diabetic patients.