Cognitive Function And Neuroimaging Characteristics In Adults With Juvenile-onset Type 1 Diabetes Mellitus

Objective: Patients with type 1 diabetes mellitus(T1DM)have been found to have mild to moderate cognitive decrements,however,the specific cognitive domains affected and the neural basis remain unclear.Since the cognitive function continues to develop during childhood and adolescence with various developmental trajectories,the age of diabetes onset may result in different cognitive function and neuroimaging characteristics.In this study,we adopted cognitive assessment and neuroimaging to investigate the cognitive function and brain imaging characteristics in adults with juvenile-onset T1 DM.Methods:(1)This study included 70,70,and 100 participants with juvenile-onset and adult-onset T1 DM,and healthy controls(HCs),respectively.All participants completed the Sustained Attention to Response Task(SART),Wisconsin Card Sorting Test(WCST),and Wechsler Memory Scale(WMS).Multivariate analyses of covariance and Jonckheere-Terpstra test were performed to examine among-group differences on cognitive functions.Hierarchical linear regression was used to investigate the influence factors.(2)The T1-weighted and diffusion tensor images were acquired in 30 juvenile-onset T1 DM patients,23 adult-onset T1 DM patients,and 60 HCs.The Tract-Based Spatial Statistics(TBSS)and Automating Fiber-Tract Quantification(AFQ)were performed to evaluate the white matter integrity.Partial correction was adopted to investigate the association between white matter tract integrity and cognitive function in juvenile-onset T1 DM group.(3)The resting-state scans were acquired in 28 juvenile-onset T1 DM patients,20 adult-onset T1 DM patients,and 60 HCs.The fractional amplitude of low frequency fluctuations(f ALFF),regional homogeneity(Re Ho),and voxel-based degree centrality(DC)analyses were performed to explore the neuron spontaneous activity and nodule centrality of whole-brain functional networks.Partial correction was adopted to investigate the association between f ALLF value,Re Ho value,DC value,and cognitive function in juvenile-onset T1 DM group.Results:(1)The juvenile-onset group showed more commission errors and shorter reaction time than HCs,more omission errors of SART than the adult-onset group(p<0.05),and lower scores on all WMS tasks than HCs(p<0.01).The adult-onset group had lower scores on WMS tasks except for immediate visual memory(p<0.01)and lower scores on perseveration errors of WSCT than HCs(p<0.05).Jonckheere-Terpstra test revealed a significant trend of juvenile-onset group<adult-onset group<HCs on SART and WMS performances.Hierarchical linear regression showed that the predict factors of cognitive functions were the history of severe hypoglycemia(SH),fasting C-peptide levels,and diabetic ketoacidosis(DKA)in the juvenile-onset group,age of onset and fasting C-peptide levels in the adult-onset group.(2)TBSS analysis showed a widespread decreased fractional anisotropy(FA)and increased mean diffusivity(MD)and radial diffusivity(RD)in adults with juvenile-onset T1 DM versus.HCs.No axial diffusivity(AD)changes were found in T1 DM group.(i)In comparison with HCs,juvenile-onset T1 DM group showed mean FA reduction,and mean MD and mean RD increase in the right corticospinal tract(CST),right inferior fronto-occipital fasciculus(IFOF),and right arcuate;mean MD and mean RD increase in bilateral uncinate;mean FA reduction in left superior longitudinal fasciculus(SLF);mean MD increase in left CST;and mean RD increase in right thalamic radiation,left IFOF,left inferior longitudinal fasciculus(ILF),and right SLF(p<0.05).Point-wise comparison revealed that the regions of significantly difference were the anterior-middle and middle-posterior component of right CST,anterior and anterior-middle component of right IFOF,and anterior and posterior component of right arcute(p<0.05).(ii)The adult-onset group showed increased mean MD in right CST compared with HCs(p<0.05),mainly in the middle component(p<0.05).(iii)Compared with adult-onset group,mean MD of right IFOF,right ILF and left arcuate,and mean RD of right IFOF were higher in juvenile-onset T1 DM group(p<0.05);point-wise comparison showed increased MD in posteromedial component of left CST and posterior component of left SLF,and increased RD in posterior component of left SLF(p<0.05).(iv)In the juvenile-onset group,mean FA,MD,and RD of right CST,mean MD and RD of right IFOF,mean RD of right SLF,mean MD of left uncinate,and mean MD and RD of right uncinate were associated with cognitive function performances(p<0.05).Besides,the white matter microstructure was influenced by age of onset,fasting blood glucose,mean hemoglobin A1c(Hb A1c)level,and body mass index in the juvenile-onset group(p<0.05).(3)The resting-state imaging analyses results:(i)In juvenile-onset T1 DM group,the f ALFF value of right precuneus,and Re Ho value of left angular gyrus,left inferior pariertal lobule,and left precuneus were lower than HCs;the f ALFF value,Re Ho value and DC value of bilateral superior temporal gyrus(STG),the f ALFF value and Reho value of left middle temporal gyrus(MTG),the Reho value of bilateral anterior cerebellum,right thalamus,right precentral gyrus and right postcentral gyrus were higher than HCs(p<0.05).(ii)In adult-onset group,the f ALFF value and Re Ho value of left dorsolateral superior frontal gyrus and left middle frontal gyrus,and the f ALFF value of right medial superior frontal gyrus were lower than HCs(p<0.05).(iii)In juvenile-onset group,the f ALFF value in left STG and MTG,Re Ho value in left anterior cerebellum,left STG and MTG,right postcentral gyrus,and DC value in right STG were associated with cognitive function performance(p<0.05).Meanwhile,mean Hb A1 c level,fasting C-peptide level,and history of DKA and SH were predict factors of brain function in juvenile-onset group.Conclusions:(1)Adults with juvenile-onset T1 DM show different cognitive function deficits characteristics when compared with adult-onset patients.(2)Adults with juvenile-onset T1 DM have widespread axonal damage and white matter integrity changes,which are consistent with the cognitive function deficits,suggesting that changes in white matter are the structural basis of cognitive impairment.(3)Adults with juvenile-onset T1 DM have abnormal resting-state brain function,which is correlated with specific impaired cognitive function,suggesting that changes in resting-state function are the functional basis of cognitive impairment.