Changes Of Cerebral Blood Flow And Its Functional Connectivity In Olfactory-related Brain Regions Of Type 2 Diabetes Mellitus

Background: Olfactory dysfunction in patients with type 2 diabetes mellitus（T2DM）may be an early marker of cognitive decline,and abnormalities in the olfactory central nervous system may be responsible for olfactory dysfunction.At present,the changes of cerebral blood flow（CBF）and its functional connectivity in olfactory-related brain regions in T2 DM are not very clear.In this study,we investigated the alteration of CBF and its functional connectivity patterns in olfactory-related brain regions of T2 DM patients based on three-dimensional pseudo-continuous arterial spin labeling（3Dpc ASL）of magnetic resonance imaging.Methods: Sixty-nine patients with T2 DM and 63 healthy controls（HC）were enrolled in this study,and all subjects underwent the smell identification test and cognitive function assessments.3D-pc ASL brain images were collected from the two groups,and the CBF of olfactory-related brain regions was acquired after post-processing.Then we compared the CBF values of olfactory-related brain regions between the two groups and analyzed the correlation between the CBF changes in olfactory-related brain regions of T2 DM and clinical parameters.We also used these olfactory-related brain regions as seed points to explore the CBF functional connectivity patterns of olfactory-related brain regions in T2 DM patients and HC,as well as the differences of CBF functional connectivity between the two groups of olfactory-related brain regions.Results: Multiple cognitive domains and olfactory identification function decreased in T2 DM patients.The CBF of the right orbital part of the inferior frontal gyrus,right insula,and bilateral olfactory cortex decreased in T2 DM patients.After controlling for age,sex,and education,the disease duration of T2 DM patients was negatively correlated with the CBF changes in the right orbital part of the inferior frontal gyrus（r=-0.248,P=0.045）,right insula（r=-0.262,P=0.033）,and right olfactory cortex（r=-0.297,P=0.016）,the CBF changes in the right orbital part of the inferior frontal gyrus were positively correlated with Self-Rating Depression Scale（SDS）scores（r=0.247,P=0.045）,the CBF changes in the right insula were negatively correlated with the max blood glucose（glu Max）of continuous glucose（r=-0.451,P=0.021）,and the CBF changes in the right olfactory cortex were negatively correlated with the mean blood glucose（glu Mean）of continuous glucose in T2 DM patients（r=-0.405,P=0.040）.Compared with the HC group,the T2 DM patients showed that the CBF functional connectivity between the right orbital part of the inferior frontal gyrus and the temporal pole of the left middle temporal gyrus decreased,the CBF functional connectivity between the right medial orbital part of the superior frontal gyrus and the right orbital part of the superior frontal gyrus increased,and the CBF functional connectivity between the right olfactory cortex and the bilateral caudate and the left putamen increased.Conclusion: T2 DM patients have decreased CBF and altered CBF functional connectivity in multiple olfactory-related brain regions.These changes may help explain why olfactory dysfunction occurs in patients with T2 DM,and these findings further reveal the neuropathological mechanism of olfactory dysfunction and cognitive decline in T2 DM patients.