Abstract
Aims: To investigate the white matter (WM) integrity and hippocampal functional connectivity (FC) in type 2 diabetes mellitus (T2DM) patients without mild cognitive impairment (MCI) by using diffusion tensor imaging (DTI) and resting-state functional magnetic resonance imaging (rs-fMRI), respectively.Methods: Twelve T2DM patients without MCI and 24 age, sex and education matched healthy controls (HC) were recruited. DTI and rs-fMRI data were subsequently acquired on a 3.0T MR scanner. Tract-based spatial statistics (TBSS) combining region of interests (ROIs) analysis was used to investigate the alterations of DTI metrics (fractional anisotropy (FA), mean diffusivity (MD), λ1 and λ23) and FC measurement was performed to calculate hippocampal FC with other brain regions. Cognitive function was evaluated by using Mini-Mental State Examination (MMSE) and Montreal Cognitive Assessment (MoCA). Brain volumes were also evaluated among these participants.Results: There were no difference of MMSE and MoCA scores between two groups. Neither whole brain nor regional brain volume decrease was revealed in T2DM patients without MCI. DTI analysis revealed extensive WM disruptions, especially in the body of corpus callosum (CC). Significant decreases of hippocampal FC with certain brain structures were revealed, especially with the bilateral frontal cortex. Furthermore, the decreased FA in left posterior thalamic radiation (PTR) and increased MD in the splenium of CC were closely related with the decreased hippocampal FC to caudate nucleus and frontal cortex.Conclusions: T2DM patients without MCI showed extensive WM disruptions and abnormal hippocampal FC. Moreover, the WM disruptions and abnormal hippocampal FC were closely associated.Highlights -T2DM patients without MCI demonstrated no obvious brain volume decrease.-Extensive white matter disruptions, especially within the body of corpus callosum, were revealed with DTI analysis among the T2DM patients.-Despite no MCI in T2DM patients, decreased functional connectivity between hippocampal region and some critical brain regions were detected.-The alterations in hippocampal functional connectivity were closely associated with those of the white matter structures in T2DM patients.This trial was registered to ClinicalTrials.gov (NCT02420470, https://www.clinicaltrials.gov/).
Highlights
The latest data released by International Diabetes Federation (IDF) shows that the global number of adults with diabetes in 2015 was 415 million, and is expected to reach 642 million by 2040; In China, that number of diabetic patients is more than 100 million of which type 2 diabetes mellitus (T2DM) accounts for 90% (International Diabetes Federation, 2015)
Neither whole brain nor regional brain volume decrease was revealed in T2DM patients without Mild cognitive impairment (MCI)
The decreased flip angle (FA) in left posterior thalamic radiation (PTR) and increased mean diffusivity (MD) in the splenium of corpus callosum (CC) were closely related with the decreased hippocampal functional connectivity (FC) to caudate nucleus and frontal cortex
Summary
The latest data released by International Diabetes Federation (IDF) shows that the global number of adults with diabetes in 2015 was 415 million, and is expected to reach 642 million by 2040; In China, that number of diabetic patients is more than 100 million of which type 2 diabetes mellitus (T2DM) accounts for 90% (International Diabetes Federation, 2015). T2DM patients with MCI were reported with decreased total gray matter (GM) volume, and middle temporal cortex volume was found to be associated with the increased MCI risk in T2DM patients (Zhang Y. et al, 2014). All these brain abnormalities were suggested to be the potential imaging biomarkers for MCI in T2DM patients. It is of significance to explore whether the brain structure or function has been affected in T2DM patients without MCI If yes, it could potentially establish early biomarkers in T2DM patients before they develop cognitive impairment and in-time interventions can be delivered to prevent or delay cognitive impairment. Whole brain or regional atrophy are not ideal biomarkers since they usually occur when T2DM patients already developed MCI
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