Structural and functional connectivity alteration patterns of the cingulate gyrus in Type 2 diabetes

Abstract

ObjectiveWe aimed to reveal the role of structural and functional alterations of cingulate gyrus in early cognitive impairment in Type 2 diabetes mellitus (T2DM) patients.MethodsFifty‐six T2DM patients and 60 healthy controls (HCs) underwent a neuropsychological assessment and sagittal three‐dimensional T1‐weighted and resting‐state functional MRI. Differences in the cortical thickness of the cingulate cortex and the functional connectivity (FC) of the nine subregions of the cingulate gyrus and the whole brain were compared between T2DM patients and HCs. Correlation analysis was performed between cortex thickness and FC and the participants' clinical/cognitive variables.ResultsThe cortical thickness of the cingulate gyrus was not significantly different between T2DM patients and HCs. However, the T2DM patients showed significantly lower FC between the pregenual ACC (pACC) and the bilateral hippocampus, significantly higher FC between the pACC and bilateral lateral prefrontal cortex (LPFC) and left precentral gyrus, and significantly lower FC between the retrosplenial cortex (RSC) and right cerebellar Crus I. The FC between the pACC and the left hippocampus was negatively correlated with the FC between the pACC and LPFC (r = −0.306, p = 0.022).InterpretationThe pACC and the RSC show dysfunctional connectivity before the appearance of structural abnormalities in T2DM patients. Abnormal FC of the pACC with the bilateral hippocampus and LPFC may imply a neural compensatory mechanism for memory function. These findings provide valuable information and new directions for possible interventions for the T2DM‐related cognitive impairment.

A systematic review of the impact of type 2 diabetes on brain cortical thickness

“…Finally, of the few discordant studies (10 out of 55) reporting no significant difference in cortical thickness between T2D and control groups, Wisse et al ( 2014 ) further describe no association either between HbA1c and global brain volume; Moran et al ( 2019 ), only the possibility of an indirect contribution with cognitive decline via its association with lower cortical thickness at baseline; in Liu et al ( 2019 ), only region-based functional connectivity impairment in T2D patients compared with the control group; and in Zhang et al ( 2023 ), T2D patients did not show cingulate gyrus thickness differences but displayed altered connectivity patterns, suggesting that functional issues may precede structural changes.…”

“…The main goal of each reviewed study was to assess the regional effects of T2D, whether in the presence or absence of other conditions, on cerebral cortical thickness as measured on T1-weighted MRI. Some studies dug deeper by, for example, evaluating the association between cognitive function and brain morphology in T2D patients, including the effect of various confounders such as age, years of education, and disease duration (Peng et al, 2014 ; Reynolds et al, 2023 ); investigating the relationship between fasting and non-fasting physiology with gray matter and white matter volume (Markus et al, 2017 ; Honea et al, 2022 ); measuring the association between neuropsychological deficits with structural and functional brain alternations (Garcia-Casares et al, 2014 ; Zhang et al, 2022 , 2023 ); or comparing the effect of metabolic and vascular factors on cortical and subcortical gray matter structural alterations (Korf et al, 2006 ; Brundel et al, 2010 ; Tchistiakova et al, 2014 ; Bernardes et al, 2018 ; Cui et al, 2023 ; Moreno et al, 2023 ; Reynolds et al, 2023 ). Other studies compared the impact of T2D on brain morphology not only against controls, but also prediabetes (Jing et al, 2023 ; Monereo-Sánchez et al, 2023 ), major depression (Ajilore et al, 2010 ) or mild cognitive impairment and Alzheimer's disease (Moran et al, 2019 ; Palix et al, 2022 ).…”

“…High glucose levels can also harm neurons, causing oxidative stress, mitochondrial dysfunction, cellular energy deficits, and neuronal dysfunction and death. Insulin plays a crucial role in neuronal survival, protein synthesis, and synaptic metabolism, and chronic hyperinsulinemia can cause insulin receptors in the blood-brain barrier to become deregulated, leading to brain insulin resistance and neural aging and degeneration (Markus et al, 2017 ; Zhang et al, 2023 ). The disruption of insulin signaling can result in impaired metabolism, synaptic plasticity, microtubule damage, and genetic activation during cell death (Markus et al, 2017 ).…”

“…We have already noted that Freesurfer was used in the majority of studies, a software that has been shown to have high accuracy and reliability in measuring cortical thickness (Gronenschild et al, 2012 ). Other toolkits included SPM8 (Garcia-Casares et al, 2014 ; Gao et al, 2023 ) and SPM12 (Roy et al, 2020 ; Palix et al, 2022 ; Zhang et al, 2022 ), MRIcroN (Roy et al, 2020 ), REST (Roy et al, 2020 ), VSRAD (Hayashi et al, 2011 ), MarsBaR (Ferreira et al, 2017 ), MEDx (Korf et al, 2006 ), PM12 (Crisóstomo et al, 2021 ) and CAT12 (Crisóstomo et al, 2021 ), Computational Anatomy Toolbox 12 (CAT12: http://www.neuro.uni-jena.de/cat/ ) (Chen et al, 2022 ; Zhang et al, 2023 ). We observed that almost all discrepant studies (6 out of 10) predominantly utilized newer versions of Freesurfer, specifically versions 5.3 and 6.0.…”