| Objective:To observe the effect of intranasal insulin on cognitive functions and to explore regulation mechanism on brain networks in Parkinson's disease by resting-state functional magnetic resonance imaging,the purpose is to provide new ideas for the treatment of PD patients and its cognitive impairment.Methods:Collect the primary PD patients diagnosed in the Neurology Outpatient Clinic of the Affiliated Hospital of North Sichuan Medical College from January 2019 to January 2020,and all subjects were evaluated by the Montreal Cognitive Assessment Scale(MoCA)and Mini-Mental State Examination(MMSE).32 PD patients with cognitive impairment(PD-CI)were randomly divided into experimental group(n=16)and control group(n=16).The experimental group was given 0.2ml(20IU)insulin(manufactured by Novo Nordisk Denmark),and the control group was given 0.2ml physiological saline via the intranasal route once a day(at the same time period)for 1 month.All subjects underwent standardized clinical characteristics assessments and rs-MRI scans pre-and post-intervention.The statistics were performed in SPSS21.0,using the statistical methods of self-paired t test,independent-sample t test and chi-square test.Using the regional homogeneity(ReHo)to analyze the rs-fMRI data of the two groups,Selecting different brain areas as regions of interest(ROI)pre-and post-intervention in the experimental group,and then the functional connectivity(FC)method based on ROI was used to performed globe-brain FC analysis.Finally to analyze the correlation between the change pre-and post-intervention ReHo and the scores of the cognitive scale in experimental group.Results:(1)Demographic and clinical characteristics:The sample included 9 subjects from experimental group and 7 subjects from control group according to the results of rs-fMRI.All subjects have no special discomfort during the experiment.No significant differences in age,gender,education years,MMSE,MoCA,H-Y stage,UPDRS,HADS scores and Levodopa equivalent daily dose(LEDD)between the two groups before intervention(P>0.05).The MMSE scores of the experimental group before and after intervention respectively were(26.00±1.73)and(26.89±1.62),the difference was statistically significant(P<0.05);MoCA scores respectively were(21.33±2.18)and(22.11±2.09),the difference was statistically significant(P<0.05);UPDRS scores respectively were(44.00±27.18)and(40.78±27.97),and the difference was statistically significant(P<0.05).There was no significant difference in MMSE,MoCA,H-Y stage,UPDRS,and HADS scores before and after in control group(P>0.05).(2)The ReHo research results:Repeated measure ANOVA revealed significant interactions for ReHo(P<0.05,Cluster>45,Alphasim corrected).Post-hoc comparison demonstrated that no statistically significant difference in ReHo between the right middle temporal gyru,the left anterior cingulate/lateral cingulate gyru,the bilateral calcarine fissure cortex,the right thalamus and the right precuneus(P>0.05).However,compared with pre-intervention,the post-intervention ReHo increased of the experimental group in the bilateral calcarine fissure cortex,the right thalamus and the right precuneus,while decrease or maintain in control group.The post-intervention ReHo increased in the right middle temporal gyru and the left anterior cingulate/lateral cingulate gyru in control group,but decreased or maintain in the experimental group.(3)FC research results:Repeated measure ANOVA revealed that compared with pre-intervention,the post-intervention FC increased between the right middle temporal gyru and the bilateral supramarginal gyrus in the experimental group,but decreased in the control group;maintained the FC with left middle frontal gyrus while the control group was increased.After intervention,the FC increase between the left anterior cingulate/lateral cingulate gyru and bilateral medial cingulate gyrus,bilateral precentral gyrus,left Parietal-inferior langular gyru,bilateral supplementary motor areas in experimental group,no decrease brain region,while the control group showed decrease or unchanged.The FC increase between the right precuneus and the left frontal middle gyru,the left dorsolateral frontal upper gyru in experimental group,while FC decrease or maintain in control group;FC weakened with the right rolandic operculum,the bilateral supramarginal gyru,and the right triangular frontal inferior gyru,right insula,right superior temporal gyru,left Parietal-inferior marginal gyru and the left middle temporal gyru,while the control group showed enhancement trend.(4)Correlation analysis results:the change of ReHo in the left anterior cingulate/lateral cingulate gyru had a positive correlation with the change test scores of UPDRS in experimental group(r=0.733,P=0.025).Although the change MoCA scores no obvious correlation between the change of ReHo in the left calcarine fissure cortex,but there is a negative correlation trend(r=-0.625,P=0.072).Conclusion:(1)After intervention of low-dose intranasal insulin,the cognitive function test scales has improved,confirming transnasal insulin can improve cognitive function of PD patients.(2)The cognitive impairment is related to the decrease activity in cognitive brain networks,especially DMN,insulin may improve the cognitive function by regulation the DMN in PD patients.(3)The change of ReHo value of the left anterior cingulate/lateral cingulate gyru in the experimental group was positively correlated with the change of UPDRS score,suggesting that insulin may have a certain extent of improvement on motor symptoms.(4)Intranasal insulin has no risk in PD patients. |
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