Hybrid PET/fMRI reveals interactive effects of T2DM and MCI on cerebral glucose metabolism and ALFF.

BACKGROUND

Type 2 diabetes mellitus (T2DM) is frequently associated with mild cognitive impairment (MCI), significantly impacting patient health, quality of life, and healthcare systems. However, the precise cerebral metabolic and functional alterations resulting from the interaction between T2DM and MCI remain incompletely understood.

METHODS

Fifty-four participants were categorized into four groups based on T2DM and MCI status. Hybrid positron emission tomography/functional magnetic resonance imaging (PET/fMRI) was used to assess cerebral glucose metabolism and the amplitude of low-frequency fluctuations (ALFF). A two-way analysis of variance evaluated the main and interactive effects of T2DM and MCI on these measures. Partial correlation analysis examined the associations between clinical variables and the observed metabolic/ALFF abnormalities.

RESULTS

Alterations in cerebral glucose metabolism in T2DM-MCI patients were primarily attributable to T2DM, with significant effects observed in the frontal, occipital, and temporal lobes, as well as subcortical regions. Both main and interactive effects of T2DM and MCI on ALFF were significant. Notably, antagonistic interactions were identified in the right superior frontal gyrus (medial orbital part) and middle frontal gyrus, suggesting that T2DM suppresses spontaneous neural activity in these regions, whereas MCI enhances it. T2DM was the principal factor influencing both metabolic and ALFF changes in the right inferior frontal gyrus (pars orbitalis). Montreal cognitive assessment scores, fasting blood glucose, and 2-hour postprandial blood glucose levels significantly correlated with neural activity alterations in regions affected by the main or interactive effects.

CONCLUSION

This hybrid PET/fMRI study identifies frontal regions where aberrant metabolic and ALFF patterns are associated with T2DM-related cognitive decline, suggesting their potential as early neuroimaging biomarkers. These findings provide new mechanistic insights and highlight possible therapeutic targets for this comorbidity.