title: Structural MRI substrates of cognitive impairment in neuromyelitis optica.
abstract: OBJECTIVE
  To identify the clinical and structural MRI markers for predicting cognitive impairment (CI) in patients with neuromyelitis optica (NMO).
  
  
  METHODS
  Fifty-four patients with NMO and 27 healthy controls underwent extensive neuropsychological testing and multimodal 3.0T MRI. The patient group was classified as CI or cognitively preserved (CP), using a criterion of ≤1.5 SD on at least 2 cognitive domains. MRI measurements included white matter (WM) lesion volume, gray matter (GM), WM, and deep GM (DGM) volume, cortical thickness, and the severity and extent of WM tract diffusion metric alterations based on fractional anisotropy and mean, axial, and radial diffusivity. Groups were compared using a multivariate general linear model, and clinical and MRI measurements were related to average cognition z scores by partial correlations and a stepwise linear regression model.
  
  
  RESULTS
  Twenty-six patients with NMO (48.2%) were classified as CI and showed WM tract diffusion abnormalities, particularly increased radial diffusivity, and GM especially DGM atrophy compared with healthy controls. Patients classified as CP also showed alterations of WM tract diffusion but without significant GM atrophy. Compared with the CP group, patients with CI demonstrated a lower level of education and decreased hippocampal volume. In the whole patient group, average cognition z scores were best predicted by the level of education and hippocampal volume (R(2) = 0.46, p < 0.001).
  
  
  CONCLUSIONS
  In patients with NMO, WM tract integrity disruption was identified in both CP and CI groups. GM atrophy, particularly in the DGM, was only found in the CI group. Hippocampal volume is the main MRI predictor of cognition in NMO.
authors.affiliation: From the Department of Neurology and Tianjin Neurological Institute (Y.L., Y.F., Nan Zhang, M.F., L.S., Y.S., Y.Y., L.Y., F.-D.S.) and Department of Radiology (Q.W., Ningnannan Zhang, C.Y.), Tianjin Medical University General Hospital, PR China; Department of Radiology and Nuclear Medicine, Neuroscience Campus Amsterdam (Y.L., M.M.S., F.B.), and Department of Anatomy and Neuroscience (M.M.S.), VU University Medical Center, Amsterdam, the Netherlands; and Department of Radiology (Y.L.), Xuanwu Hospital, Capital Medical University, Beijing, PR China. asiaeurope80@gmail.com yfu@tmu.edu.cn.
authors.forename: Yaou
authors.initials: Y
authors.lastname: Liu
authors.affiliation: From the Department of Neurology and Tianjin Neurological Institute (Y.L., Y.F., Nan Zhang, M.F., L.S., Y.S., Y.Y., L.Y., F.-D.S.) and Department of Radiology (Q.W., Ningnannan Zhang, C.Y.), Tianjin Medical University General Hospital, PR China; Department of Radiology and Nuclear Medicine, Neuroscience Campus Amsterdam (Y.L., M.M.S., F.B.), and Department of Anatomy and Neuroscience (M.M.S.), VU University Medical Center, Amsterdam, the Netherlands; and Department of Radiology (Y.L.), Xuanwu Hospital, Capital Medical University, Beijing, PR China. asiaeurope80@gmail.com yfu@tmu.edu.cn.
authors.forename: Ying
authors.initials: Y
authors.lastname: Fu
authors.affiliation: From the Department of Neurology and Tianjin Neurological Institute (Y.L., Y.F., Nan Zhang, M.F., L.S., Y.S., Y.Y., L.Y., F.-D.S.) and Department of Radiology (Q.W., Ningnannan Zhang, C.Y.), Tianjin Medical University General Hospital, PR China; Department of Radiology and Nuclear Medicine, Neuroscience Campus Amsterdam (Y.L., M.M.S., F.B.), and Department of Anatomy and Neuroscience (M.M.S.), VU University Medical Center, Amsterdam, the Netherlands; and Department of Radiology (Y.L.), Xuanwu Hospital, Capital Medical University, Beijing, PR China.
authors.forename: Menno M
authors.initials: MM
authors.lastname: Schoonheim
authors.affiliation: From the Department of Neurology and Tianjin Neurological Institute (Y.L., Y.F., Nan Zhang, M.F., L.S., Y.S., Y.Y., L.Y., F.-D.S.) and Department of Radiology (Q.W., Ningnannan Zhang, C.Y.), Tianjin Medical University General Hospital, PR China; Department of Radiology and Nuclear Medicine, Neuroscience Campus Amsterdam (Y.L., M.M.S., F.B.), and Department of Anatomy and Neuroscience (M.M.S.), VU University Medical Center, Amsterdam, the Netherlands; and Department of Radiology (Y.L.), Xuanwu Hospital, Capital Medical University, Beijing, PR China.
authors.forename: Nan
authors.initials: N
authors.lastname: Zhang
authors.affiliation: From the Department of Neurology and Tianjin Neurological Institute (Y.L., Y.F., Nan Zhang, M.F., L.S., Y.S., Y.Y., L.Y., F.-D.S.) and Department of Radiology (Q.W., Ningnannan Zhang, C.Y.), Tianjin Medical University General Hospital, PR China; Department of Radiology and Nuclear Medicine, Neuroscience Campus Amsterdam (Y.L., M.M.S., F.B.), and Department of Anatomy and Neuroscience (M.M.S.), VU University Medical Center, Amsterdam, the Netherlands; and Department of Radiology (Y.L.), Xuanwu Hospital, Capital Medical University, Beijing, PR China.
authors.forename: Moli
authors.initials: M
authors.lastname: Fan
authors.affiliation: From the Department of Neurology and Tianjin Neurological Institute (Y.L., Y.F., Nan Zhang, M.F., L.S., Y.S., Y.Y., L.Y., F.-D.S.) and Department of Radiology (Q.W., Ningnannan Zhang, C.Y.), Tianjin Medical University General Hospital, PR China; Department of Radiology and Nuclear Medicine, Neuroscience Campus Amsterdam (Y.L., M.M.S., F.B.), and Department of Anatomy and Neuroscience (M.M.S.), VU University Medical Center, Amsterdam, the Netherlands; and Department of Radiology (Y.L.), Xuanwu Hospital, Capital Medical University, Beijing, PR China.
authors.forename: Lei
authors.initials: L
authors.lastname: Su
authors.affiliation: From the Department of Neurology and Tianjin Neurological Institute (Y.L., Y.F., Nan Zhang, M.F., L.S., Y.S., Y.Y., L.Y., F.-D.S.) and Department of Radiology (Q.W., Ningnannan Zhang, C.Y.), Tianjin Medical University General Hospital, PR China; Department of Radiology and Nuclear Medicine, Neuroscience Campus Amsterdam (Y.L., M.M.S., F.B.), and Department of Anatomy and Neuroscience (M.M.S.), VU University Medical Center, Amsterdam, the Netherlands; and Department of Radiology (Y.L.), Xuanwu Hospital, Capital Medical University, Beijing, PR China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Shen
authors.affiliation: From the Department of Neurology and Tianjin Neurological Institute (Y.L., Y.F., Nan Zhang, M.F., L.S., Y.S., Y.Y., L.Y., F.-D.S.) and Department of Radiology (Q.W., Ningnannan Zhang, C.Y.), Tianjin Medical University General Hospital, PR China; Department of Radiology and Nuclear Medicine, Neuroscience Campus Amsterdam (Y.L., M.M.S., F.B.), and Department of Anatomy and Neuroscience (M.M.S.), VU University Medical Center, Amsterdam, the Netherlands; and Department of Radiology (Y.L.), Xuanwu Hospital, Capital Medical University, Beijing, PR China.
authors.forename: Yaping
authors.initials: Y
authors.lastname: Yan
authors.affiliation: From the Department of Neurology and Tianjin Neurological Institute (Y.L., Y.F., Nan Zhang, M.F., L.S., Y.S., Y.Y., L.Y., F.-D.S.) and Department of Radiology (Q.W., Ningnannan Zhang, C.Y.), Tianjin Medical University General Hospital, PR China; Department of Radiology and Nuclear Medicine, Neuroscience Campus Amsterdam (Y.L., M.M.S., F.B.), and Department of Anatomy and Neuroscience (M.M.S.), VU University Medical Center, Amsterdam, the Netherlands; and Department of Radiology (Y.L.), Xuanwu Hospital, Capital Medical University, Beijing, PR China.
authors.forename: Li
authors.initials: L
authors.lastname: Yang
authors.affiliation: From the Department of Neurology and Tianjin Neurological Institute (Y.L., Y.F., Nan Zhang, M.F., L.S., Y.S., Y.Y., L.Y., F.-D.S.) and Department of Radiology (Q.W., Ningnannan Zhang, C.Y.), Tianjin Medical University General Hospital, PR China; Department of Radiology and Nuclear Medicine, Neuroscience Campus Amsterdam (Y.L., M.M.S., F.B.), and Department of Anatomy and Neuroscience (M.M.S.), VU University Medical Center, Amsterdam, the Netherlands; and Department of Radiology (Y.L.), Xuanwu Hospital, Capital Medical University, Beijing, PR China.
authors.forename: Qiuhui
authors.initials: Q
authors.lastname: Wang
authors.affiliation: From the Department of Neurology and Tianjin Neurological Institute (Y.L., Y.F., Nan Zhang, M.F., L.S., Y.S., Y.Y., L.Y., F.-D.S.) and Department of Radiology (Q.W., Ningnannan Zhang, C.Y.), Tianjin Medical University General Hospital, PR China; Department of Radiology and Nuclear Medicine, Neuroscience Campus Amsterdam (Y.L., M.M.S., F.B.), and Department of Anatomy and Neuroscience (M.M.S.), VU University Medical Center, Amsterdam, the Netherlands; and Department of Radiology (Y.L.), Xuanwu Hospital, Capital Medical University, Beijing, PR China.
authors.forename: Ningnannan
authors.initials: N
authors.lastname: Zhang
authors.affiliation: From the Department of Neurology and Tianjin Neurological Institute (Y.L., Y.F., Nan Zhang, M.F., L.S., Y.S., Y.Y., L.Y., F.-D.S.) and Department of Radiology (Q.W., Ningnannan Zhang, C.Y.), Tianjin Medical University General Hospital, PR China; Department of Radiology and Nuclear Medicine, Neuroscience Campus Amsterdam (Y.L., M.M.S., F.B.), and Department of Anatomy and Neuroscience (M.M.S.), VU University Medical Center, Amsterdam, the Netherlands; and Department of Radiology (Y.L.), Xuanwu Hospital, Capital Medical University, Beijing, PR China.
authors.forename: Chunshui
authors.initials: C
authors.lastname: Yu
authors.affiliation: From the Department of Neurology and Tianjin Neurological Institute (Y.L., Y.F., Nan Zhang, M.F., L.S., Y.S., Y.Y., L.Y., F.-D.S.) and Department of Radiology (Q.W., Ningnannan Zhang, C.Y.), Tianjin Medical University General Hospital, PR China; Department of Radiology and Nuclear Medicine, Neuroscience Campus Amsterdam (Y.L., M.M.S., F.B.), and Department of Anatomy and Neuroscience (M.M.S.), VU University Medical Center, Amsterdam, the Netherlands; and Department of Radiology (Y.L.), Xuanwu Hospital, Capital Medical University, Beijing, PR China.
authors.forename: Frederik
authors.initials: F
authors.lastname: Barkhof
authors.affiliation: From the Department of Neurology and Tianjin Neurological Institute (Y.L., Y.F., Nan Zhang, M.F., L.S., Y.S., Y.Y., L.Y., F.-D.S.) and Department of Radiology (Q.W., Ningnannan Zhang, C.Y.), Tianjin Medical University General Hospital, PR China; Department of Radiology and Nuclear Medicine, Neuroscience Campus Amsterdam (Y.L., M.M.S., F.B.), and Department of Anatomy and Neuroscience (M.M.S.), VU University Medical Center, Amsterdam, the Netherlands; and Department of Radiology (Y.L.), Xuanwu Hospital, Capital Medical University, Beijing, PR China.
authors.forename: Fu-Dong
authors.initials: FD
authors.lastname: Shi
mesh_terms: D000328:Adult; D016880:Anisotropy; D001284:Atrophy; D001921:Brain / Q000473:pathology; D016022:Case-Control Studies; D002540:Cerebral Cortex / Q000473:pathology*; D003072:Cognition Disorders / Q000209:etiology / Q000473:pathology* / Q000523:psychology; D015331:Cohort Studies; D056324:Diffusion Tensor Imaging; D004522:Educational Status; D005260:Female; D066128:Gray Matter / Q000473:pathology*; D006624:Hippocampus / Q000473:pathology*; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D009471:Neuromyelitis Optica / Q000150:complications / Q000473:pathology* / Q000523:psychology; D009483:Neuropsychological Tests; D009929:Organ Size; D066127:White Matter / Q000473:pathology*