Amide proton transfer imaging reveals cerebral metabolic alterations associated with cognitive impairment in type 2 diabetes mellitus.

Background: Amide proton transfer (APT) imaging indirectly reflects tissue metabolic changes by detecting variations in the concentration of mobile amide protons and tissue pH. Type 2 diabetes mellitus (T2DM) is often accompanied by cognitive dysfunction and diabetic encephalopathy, both of which pose serious threat to human health and quality of life. This study aimed to evaluate the potential of APT imaging as a novel biomarker for detecting cerebral metabolic alterations and to investigate its associations with cognitive impairment in patients with T2DM.

Methods: This study included 32 T2DM patients, comprising 16 with mild cognitive impairment (MCI) and 16 with normal cognition (NC), and 26 healthy controls. Clinical data and cognitive assessments were collected within one week of MRI acquisition. Imaging markers of cerebral small vessel disease (CSVD) were evaluated using AI-assisted tools. APT values were measured in predefined brain regions, including the hippocampus (hipp), temporal white matter (TWM), temporal gray matter (TGM), occipital white matter (OWM), occipital gray matter (OGM), and cerebral peduncles (CPs) using 3D Slicer software. Group differences were analyzed with one-way ANOVA followed by Bonferroni-corrected post hoc tests (or Kruskal-Wallis test with Bonferroni correction for non-parametric data). Partial correlations (Bonferroni-corrected) assessed the links between APT values and cognitive scores, as well as between APT values and CSVD imaging markers.

Results: The APT values of the left temporal white matter (TWM) and the right temporal gray matter (TGM) were significantly different among the three groups. Among them, the APT values of T2DM-MCI group were significantly lower. In T2DM patients, partial correlation analysis showed that the APT values of the left TWM was positively correlated with MMSE attention and calculation score, MoCA attention score, and the number of lacunar infarcts (LI), and negatively correlated with the severity of white matter hyperintensities (WMH). The APT values of right TGM was positively correlated with MoCA total scores, MoCA visuospatial scores and MoCA delayed recall scores.

Conclusion: T2DM patients with mild cognitive impairment exhibited significantly lower APT values in the left temporal white matter and right temporal gray matter. These lower APT values were strongly associated with poorer cognitive performance and more severe CSVD. APT imaging may serve as a sensitive, noninvasive biomarker for detecting cerebral metabolic deterioration underlying diabetic cognitive decline.