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Research ArticleAdult Brain

Reduced Global Efficiency and Random Network Features in Patients with Relapsing-Remitting Multiple Sclerosis with Cognitive Impairment

R. Hawkins, A.S. Shatil, L. Lee, A. Sengupta, L. Zhang, S. Morrow and R.I. Aviv
American Journal of Neuroradiology March 2020, 41 (3) 449-455; DOI: https://doi.org/10.3174/ajnr.A6435
R. Hawkins
aFrom the Department of Medical Imaging (R.H., A.S.S., A.S., L.Z.)
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A.S. Shatil
aFrom the Department of Medical Imaging (R.H., A.S.S., A.S., L.Z.)
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L. Lee
bDivision of Neurology (L.L.), Department of Medicine, Sunnybrook Health Sciences Centre, Toronto, Ontario, Canada
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A. Sengupta
aFrom the Department of Medical Imaging (R.H., A.S.S., A.S., L.Z.)
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L. Zhang
aFrom the Department of Medical Imaging (R.H., A.S.S., A.S., L.Z.)
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S. Morrow
cDivision of Neurology (S.M.), Lawson Health Research Institute, London Health Sciences Centre, University Hospital, London, Ontario, Canada
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R.I. Aviv
dInstitute of Biomaterials and Biomedical Engineering (R.I.A.), University of Toronto, Toronto, Ontario, Canada
eDepartment of Radiology (R.I.A.), University of Ottawa, and Division of Neuroradiology, The Ottawa Hospital, Ottawa, Ontario, Canada.
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    Figure.

    Pearson correlations (edges) between all pairs of GM regions (nodes) for a group of subjects. Here the rows/columns denote the nodes, and the warmer colors represent the greater edge weights/connectivity between the nodes. The colored matrices (left column) here show the weighted undirected network, where the edges are associated with the strength of the connection and are undirected (ie, if node j is connected to node k, then node k is also connected to node j), resulting in a symmetric connectivity matrix. The black-white matrices are binary undirected networks, where edges are either 0 or 1, indicating the absence or presence of a connection, and they have no directionality. Nodal correlations are proportional to longer path length. MS-CI shows a warmer matrix than MS-CP or HC.

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    Table 1:

    Demographic and clinical characteristics of healthy controls and patients with MS

    CharacteristicsHCMS
    Total SampleMS-CPMS-CI
    No.18805525
    Female sex (No.) (%)13 (72%)54 (68%)41 (75%)13 (52%)a
    Age (mean) (SD) (yr)48.7 (7.2)51.8 (8.6)52.7 (8.8)49.7 (7.9)
    Education (mean) (SD) (yr)17.0 (2.9)15.0 (2.4)b15.2 (2.2)14.6 (2.7)
    Disease duration (mean) (SD) (yr)NA15.8 (8.9)15.7 (8.4)15.9 (9.9)
    EDSS (mean) (SD)NA4.3 (2.3)4.1 (2.4)4.6 (2.2)
    T1 lesion load (mean) (SD)NA4.0 (5.6)2.8 (3.3)6.7 (8.3)c
    T2 lesion load (mean) (SD)NA15.8 (15.8)11.8 (11.2)24.6 (20.5)c
    Global gray matter volume (mean) (SD)875.9 (48.9)748.5 (69.6)d761.2 (65.9)720.6 (70.8)a
    NAWM volume (mean) (SD)616.2 (39.9)510.9 (101.3)d540.9 (56.3)444.7 (141.5)e
    Neurocognitive domain score (mean) (SD)
     Processing−0.17 (0.74)−0.90 (0.99)e−0.43 (0.68)−2.01 (0.65)f
     Learning0.12 (0.73)−0.80 (1.29)e−0.093 (0.76)−2.35 (0.74)f
     Executive functioning0.50 (0.75)−0.062 (1.12)0.30 (0.80)−0.85 (1.32)f
     Visual0.98 (0.20)0.55 (0.91)0.79 (0.86)0.010 (0.80)f
     Language−0.70 (0.84)−0.86 (1.05)−0.56 (0.84)−1.53 (1.17)f
    Average z score0.15 (0.41)−0.42 (0.80)e−0.003 (0.48)−1.34 (0.54)f
    • Note:—NA indicates not applicable; EDSS, Expanded Disability Status Scale.

    • a Adjusted P < .05 (comparison within MS groups is based on cognitive impairment status).

    • b Adjusted P < .05 (comparison of total sample of MS patients with healthy control).

    • c Adjusted P < .01 (comparison within MS groups is based on cognitive impairment status).

    • ↵d Adjusted P < .001 (comparison of total sample of MS patients with healthy control).

    • ↵e Adjusted P < .01 (comparison of total sample of MS patients with healthy control).

    • ↵f Adjusted P < .001 (comparison within MS groups is based on cognitive impairment status).

    • View popup
    Table 2:

    Values of global gray matter network properties between HC and patients with MS and within the MS sample based on cognitive statusa

    Network Properties (Mean) (SD)HCMS
    Total SampleMS-CPMS-CI
    No.18805525
    Size6950.17 (700.80)6677.81 (589.84)6607.64 (575.60)6832.20 (603.02)
    Degree1234.59 (129.73)1064.42 (124.89)b1080.08 (113.24)1029.97 (143.86)
    Density (%)17.77 (0.77)15.97 (1.59)16.37 (1.31)15.10 (1.82)
    Clustering0.439 (0.013)0.396 (0.034)0.405 (0.027)0.377 (0.040)
    Betweenness5998.11 (609.99)5816.27 (534.55)5741.29 (513.53)5981.22 (553.17)
    Path length1.863 (0.009)1.871 (0.014)b1.869 (0.012)1.875 (0.016)
    γ1.086 (0.003)1.081 (0.005)1.081 (0.004)1.079 (0.006)
    λ1.021 (0.003)1.015 (0.004)b1.016 (0.003)1.012 (0.004)c
    Small world1.064 (0.003)1.065 (0.004)1.064 (0.004)1.067 (0.005)
    • ↵a HC versus MS group was statistically compared taking into account sex, education, and global gray matter volume; and the MS-CP versus MS-CI groups were compared with 2 additional confounding factors of T1 and T2 lesion loads (log). Data are corrected for multiple comparisons.

    • ↵b Adjusted P < .05 (comparison of total sample of MS patients with healthy control).

    • ↵c Adjusted P < .01 (comparison within MS group based on cognitive impairment status).

    • View popup
    Table 3:

    Predictors of neurocognitive domain scores in total groups of patients with MSa

    Standardized Coefficients βComparing with the Reference Modelb (G2) (P Value)
    β (95% CI)Significance
    Processing (R2 = 43.6%)20.9 (<.0001)
     NAWM volume0.298 (0.047–0.616).0229
     λ0.548 (0.236–0.895).0011
    Learning (R2 = 40.4%)26.1 (<.0001)
     Education0.205 (0.022–0.388).0283
     T1 lesion loads (log)−0.300 (−0.581 to −0.019).0369
     λ0.622 (0.332–0.913)<.0001
    Executive functioning (R2 = 41.0%)4.4 (.1108)
     Education0.354 (0.170–0.539).0003
     NAWM volume0.274 (0.020–0.527).0348
     Degree0.313 (0.095–0.531).0055
    Visual (R2 = 27.5%)9.2 (.0024)
     Sex (M/F)0.293 (0.056–0.530).0160
     T2 lesion loads (log)0.367 (0.204–0.714).0383
     Density (%)0.523 (0.236–0.809).0005
    Language (R2 = 35.8%)7.9 (.0953)
     EDSS (log)−0.376 (−0.648 to −0.104).0074
     Disease duration (log)0.224 (0.007–0.441).0433
     NAWM volume0.318 (0.037–0.600).0274
     Degree−0.254 (−0.486 to −0.021).0330
    Average score (R2 = 56.2%)21.3 (<.0001)
     Education0.305 (0.139–0.471).0005
     T1 lesion loads (log)−0.261 (−0.515 to −0.008).0434
     NAWM volume0.343 (0.109–0.576).0046
     λ0.404 (0.12–0.696).0073
    • ↵a Backward stepwise elimination multivariable regression was conducted after accounting for sex, education, global gray matter volume, and T1 and T2 lesion loads (log). The Table shows the best regression model for each dependent variable (neurocognitive domain scores).

    • ↵b Reference model included only confounding factors of sex, education, global gray matter volume, and T1 and T2 lesion loads (log). The G2 likelihood ratio test was used to compare the best regression model with the reference model. P  < .05 was considered statistically significant.

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R. Hawkins, A.S. Shatil, L. Lee, A. Sengupta, L. Zhang, S. Morrow, R.I. Aviv
Reduced Global Efficiency and Random Network Features in Patients with Relapsing-Remitting Multiple Sclerosis with Cognitive Impairment
American Journal of Neuroradiology Mar 2020, 41 (3) 449-455; DOI: 10.3174/ajnr.A6435

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Reduced Global Efficiency and Random Network Features in Patients with Relapsing-Remitting Multiple Sclerosis with Cognitive Impairment
R. Hawkins, A.S. Shatil, L. Lee, A. Sengupta, L. Zhang, S. Morrow, R.I. Aviv
American Journal of Neuroradiology Mar 2020, 41 (3) 449-455; DOI: 10.3174/ajnr.A6435
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