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This study investigates how type 2 diabetes mellitus (T2DM) and mild cognitive impairment (MCI) impact brain metabolism and neural function.

May 10, 2026Scientific Reports0 citationsOpen Access

Simultaneous PET/fMRI distinguishes the separate and synergistic effects of T2DM and MCI on cerebral glucose metabolism and fALFF

CZCuihua Zhao JLJiao Liu RCRuitian Cheng

Key Points

This study investigates how type 2 diabetes mellitus (T2DM) and mild cognitive impairment (MCI) impact brain metabolism and neural function.
Fifty-four participants categorized into four groups based on T2DM and MCI status.
Simultaneous PET and fMRI assessed cerebral glucose metabolism and fALFF.
Two-way analysis of variance evaluated the main and interactive effects of T2DM and MCI.
Alterations in glucose metabolism in the T2DM-MCI group were primarily due to T2DM, affecting multiple brain regions.
A synergistic interaction between T2DM and MCI was found in the right amygdala, increasing neural activity.
Negative correlation between fALFF in the left superior frontal gyrus and cognitive scores in MCI groups, with specific findings in the T2DM-MCI group.

Abstract

Type 2 diabetes mellitus (T2DM) is a recognized risk factor for mild cognitive impairment (MCI), yet the combined effects of T2DM and MCI on cerebral metabolism and neural activity remain poorly characterized. Fifty-four participants were categorized into four groups based on the presence of T2DM and MCI. Simultaneous positron emission tomography (PET) and functional magnetic resonance imaging (fMRI) was used to assess cerebral glucose metabolism and the fractional amplitude of low-frequency fluctuations (fALFF). The main and interactive effects of T2DM and MCI were evaluated using the two-way analysis of variance. Partial correlation analyses were conducted to examine the relationships between clinical variables and cognitive scores and neuroimaging measures. Changes in glucose metabolism in the T2DM-MCI group were primarily attributable to T2DM, with significant alterations observed across frontal, occipital, and temporal lobes, as well as subcortical areas. Both main and interactive effects of T2DM and MCI were identified for fALFF. A synergistic interaction between T2DM and MCI was found specifically in the right amygdala, where their combined presence was associated with amplified intrinsic neural activity. Moreover, in the right angular gyrus (ANG), T2DM emerged as the predominant factor underlying concurrent reductions in glucose metabolism and fALFF. Clinically, fALFF in the left superior frontal gyrus-medial orbital showed a significant negative correlation with Montreal Cognitive Assessment scores in both MCI and T2DM-MCI groups, while fALFF in the right amygdala was positively correlated with Mini-Mental State Examination scores in the T2DM-MCI group. This PET/fMRI study establishes T2DM as a key driver of coupled metabolic and functional deficits in the right ANG and reveals a synergistic interaction with MCI that amplifies neural activity in the amygdala. These findings position the ANG and amygdala as potential early biomarkers for T2DM-related cognitive decline, offering new insights into mechanisms and potential therapies.

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