The objective of this study was to investigate alterations in functional connectivity density (FCD) mapping and their impact on functional connectivity (FC) among individuals diagnosed with Type 2 diabetes mellitus (T2DM) across different cognitive states. Moreover, the study sought to explore the potential association between aberrant FCD/FC patterns and clinical or cognitive variables. A total of 211 participants were recruited for this study, consisting of 75 healthy controls (HCs), 89 T2DM patients with normal cognitive function (DMCN), and 47 T2DM patients with mild cognitive impairment (DMCI). The study employed FCD analysis to pinpoint brain regions exhibiting significant FCD alterations. Subsequently, these regions showing abnormal FCD served as seeds for FC analysis. Exploratory partial correlations were conducted to explore the relationship between clinical biochemical indicators, neuropsychological test scores, and altered FCD or FC. The FCD analysis revealed an increased trend in global FCD (gFCD), local FCD (lFCD), and long-range FCD (lrFCD) within the bilateral supramarginal gyrus (SMG) among individuals with DMCN. Additionally, significant lFCD alterations were observed in the right inferior frontal gyrus and left precuneus when comparing DMCN to HCs and DMCI. When comparing individuals with T2DM and healthy controls (HCs), it was revealed that DMCN exhibited significant improvements in FCD. This suggests that the brain may employ specific compensatory mechanisms to maintain normal cognitive function at this stage. Our findings provide a novel perspective on the neural mechanisms involved in cognitive decline associated with T2DM.
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