title: Disrupted subject-specific gray matter network properties and cognitive dysfunction in type 1 diabetes patients with and without proliferative retinopathy.
abstract: BACKGROUND
  Type 1 diabetes mellitus (T1DM) patients, especially with concomitant microvascular disease, such as proliferative retinopathy, have an increased risk of cognitive deficits. Local cortical gray matter volume reductions only partially explain these cognitive dysfunctions, possibly because volume reductions do not take into account the complex connectivity structure of the brain. This study aimed to identify gray matter network alterations in relation to cognition in T1DM.
  
  
  METHODS
  We investigated if subject-specific structural gray matter network properties, constructed from T1-weighted MRI scans, were different between T1DM patients with (n = 51) and without (n = 53) proliferative retinopathy versus controls (n = 49), and were associated to cognitive decrements and fractional anisotropy, as measured by voxel-based TBSS. Global normalized and local (45 bilateral anatomical regions) clustering coefficient and path length were assessed. These network properties measure how the organization of connections in a network differs from that of randomly connected networks.
  
  
  RESULTS
  Global gray matter network topology was more randomly organized in both T1DM patient groups versus controls, with the largest effects seen in patients with proliferative retinopathy. Lower local path length values were widely distributed throughout the brain. Lower local clustering was observed in the middle frontal, postcentral, and occipital areas. Complex network topology explained up to 20% of the variance of cognitive decrements, beyond other predictors. Exploratory analyses showed that lower fractional anisotropy was associated with a more random gray matter network organization.
  
  
  CONCLUSIONS
  T1DM and proliferative retinopathy affect cortical network organization that may consequently contribute to clinically relevant changes in cognitive functioning in these patients.
authors.affiliation: Diabetes Center/Department of Internal Medicine, VU University Medical Center, Amsterdam, The Netherlands.|Department of Medical Psychology, VU University Medical Center, Amsterdam, The Netherlands.|Department of Psychology, Pontifícia Universidade Católica, Rio De Janeiro, Brasil.
authors.forename: Eelco
authors.initials: E
authors.lastname: van Duinkerken
authors.affiliation: Diabetes Center/Department of Internal Medicine, VU University Medical Center, Amsterdam, The Netherlands.
authors.forename: Richard G
authors.initials: RG
authors.lastname: Ijzerman
authors.affiliation: Department of Medical Psychology, VU University Medical Center, Amsterdam, The Netherlands.
authors.forename: Martin
authors.initials: M
authors.lastname: Klein
authors.affiliation: Department of Ophthalmology, VU University Medical Center, Amsterdam, The Netherlands.
authors.forename: Annette C
authors.initials: AC
authors.lastname: Moll
authors.affiliation: Department of Medical Psychology, VU University Medical Center, Amsterdam, The Netherlands.|Department of Medical Psychology, Academic Medical Center, Amsterdam, The Netherlands.
authors.forename: Frank J
authors.initials: FJ
authors.lastname: Snoek
authors.affiliation: Alzheimer Center/Department of Neurology, VU University Medical Center, Amsterdam, The Netherlands.
authors.forename: Philip
authors.initials: P
authors.lastname: Scheltens
authors.affiliation: Department of Physics and Medical Technology, VU University Medical Center, Amsterdam, The Netherlands.
authors.forename: Petra J W
authors.initials: PJ
authors.lastname: Pouwels
authors.affiliation: Department of Radiology and Nuclear Medicine, VU University Medical Center, Amsterdam, The Netherlands.
authors.forename: Frederik
authors.initials: F
authors.lastname: Barkhof
authors.affiliation: Diabetes Center/Department of Internal Medicine, VU University Medical Center, Amsterdam, The Netherlands.
authors.forename: Michaela
authors.initials: M
authors.lastname: Diamant
authors.affiliation: Alzheimer Center/Department of Neurology, VU University Medical Center, Amsterdam, The Netherlands.
authors.forename: Betty M
authors.initials: BM
authors.lastname: Tijms
mesh_terms: D000328:Adult; D001921:Brain / Q000473:pathology*; D003071:Cognition; D003072:Cognition Disorders / Q000473:pathology* / Q000503:physiopathology; D003922:Diabetes Mellitus, Type 1 / Q000473:pathology* / Q000503:physiopathology / Q000523:psychology; D003930:Diabetic Retinopathy / Q000473:pathology* / Q000503:physiopathology / Q000523:psychology; D056324:Diffusion Tensor Imaging; D005260:Female; D066128:Gray Matter / Q000473:pathology*; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D009434:Neural Pathways / Q000473:pathology; D009483:Neuropsychological Tests; D009929:Organ Size; D066127:White Matter / Q000473:pathology
keywords: cognition; graph theory; microangiopathy; neuroimaging; small worldness; type 1 diabetes