Increased resting state functional irregularity of T2DM brains with high HbA1c: sign for impaired verbal memory function?

Glycosylated hemoglobin A1c (HbA1c) has been considered as a key contributor to impaired cognition in type 2 diabetes mellitus (T2DM) brains. However, how does it affect the brain and whether the glucose controlling can slow down the process are still unknown. In the current study, T2DM patients with high glycosylated hemoglobin level (HGL) and controls with normal glycosylated hemoglobin level (NGL) were enrolled to investigate the relationships between HbA1c, brain imaging characteristics and cognitive function. First, a series of cognitive tests including California Verbal Learning Test (CVLT) were conducted. Then, the functional irregularity based on resting state functional magnetic resonance imaging data was evaluated via a new data-driven brain entropy (BEN) mapping analysis method. We found that the HGLs exhibited significantly increased BEN in the right precentral gyrus (PreCG.R), the right middle frontal gyrus (MFG.R), the triangular and opercular parts of the right inferior frontal gyrus (IFGtriang.R and IFGoperc.R). The strengths of the functional connections of PreCG.R with the brainstem/cerebellum were decreased. Partial correlation analysis showed that HbA1c had a strong positive correlation to regional BEN and negatively correlated with some CVLT scores. Negative correlations also existed between the BEN of PreCG.R/IFGoperc.R and some CVLT scores, suggesting the correspondence between higher HbA1c, increased BEN and decreased verbal memory function. This study demonstrated the potential of BEN in exploring the functional alterations affected by HbA1c and interpreting the verbal memory function decline. It will help understanding the neurophysiological mechanism of T2DM-induced cognitive decline and taking effective prevention or treatment measures.