# Contribution of Gray and White Matter Abnormalities to Cognitive Impairment in Multiple Sclerosis
## 4 Materials and Methods
### MRI Image Acquisition and Analysis  
Brain images were obtained using a 3.0T MRI (GE 750, Waukesha, WI, USA) with a 32-channel head coil covering the whole brain. The experimental protocol included DTI images, as well as T1 and T2-weighted images.  
The main sequences were performed with the following parameters:  
1. DTI sequence: echo time (TE) = minimum, repetition time (TR) = 10,000, field of view (FOV) 240 mm, matrix 128 mm \(\times\) 128 mm, slice thickness 3.0 mm, \(b\)-value = 1000, number of slices = 44, number of directions = 25, and 0 skip between slices.
2. Three-dimensional T1-weighted magnetization-fast spoiled gradient recalled echo (T1 WI 3D-FSPGR) images: TE = min/full, flip angle 8\({}^{\circ}\), slice thickness 1.2 mm, rep time = 900, matrix 256 mm \(\times\) 256 mm, and 0 skip between slices. High-resolution T1-weighted images were obtained for VBM analyses.  
\begin{table}
\begin{tabular}{c c c c} \hline
**Characteristic** & **Patients with MS (CP) \(n\) = 25** & **Patients with MS (CI) \(n\) = 14** & \(p\) \\ \hline Age, y & 37.92 \(\pm\) 9.24 & 38.86 \(\pm\) 9.02 & 0.76 \\ Age at onset, y & 32.08 \(\pm\) 10.52 & 29.71 \(\pm\) 8.93 & 0.48 \\ Years of education & 13.04 \(\pm\) 2.99 & 9.85 \(\pm\) 3.00 & 0.01 \\ Disease duration (m) & 80.72 \(\pm\) 71.38 & 113.07 \(\pm\) 59.50 & 0.18 \\ Annualized relapse rate & 0.51 \(\pm\) 0.47 & 0.58 \(\pm\) 0.45 & 0.66 \\ EDSS score & 1.00 (1.00–2.00) & 3.50 (2.00–4.60) & \textless{}0.01 \\ HAMA & 6.40 \(\pm\) 3.66 & 11.79 \(\pm\) 6.18 & \textless{}0.01 \\ HAMD & 5.12 \(\pm\) 3.46 & 9.71 \(\pm\) 4.53 & \textless{}0.01 \\ \hline \end{tabular} Normally distributed data are the means \(\pm\) SD and analyzed by the independent-samples \(t\)-test. Non-normally-distributed parameters are the median (interquartile range) and analyzed by the Mann-Whitney \(U\)-test. Abbreviations: CP = cognitive preservation; CI = cognitive impairment; EDSS = Expanded Disability Status Scale; HAMA = Hamilton Anxiety Scale; HAMD = Hamilton Depression Scale; y = year; m = month.  
\end{table}
Table 6: Demographic and clinical characteristics of the MS patients with CI and CP.  
\begin{table}
\begin{tabular}{c c c} \hline
**Cognitive Test** & **HC (\(n\) = 29)** & **Patients with MS (CP) (\(n\) = 25)** & **Patients with MS (CI) (\(n\) = 1)** \\ \hline AVLT-Total recall & 0.00 \(\pm\) 1.47 & 0.05 \(\pm\) 1.14 & \(-\)2.33\(\pm\) 1.74 \({}^{\text{a.c}}\) \\ AVLT-Delayed recall & 0.00 \(\pm\) 1.00 & 0.20 \(\pm\) 0.79 & \(-\)1.74 \(\pm\) 1.53 \({}^{\text{a.c}}\) \\ VFT & 0.00 \(\pm\) 1.00 & \(-\)0.02 \(\pm\) 0.81 & \(-\)0.85 \(\pm\) 0.73 \({}^{\text{a.c}}\) \\ SDMT & 0.00 \(\pm\) 1.00 & \(-\)0.19 \(\pm\) 0.86 & \(-\)1.97 \(\pm\) 1.08 \\ TMT-A & 0.00 \(\pm\) 1.00 & \(-\)0.18 \(\pm\) 0.66 & 2.48 \(\pm\) 2.37 \({}^{\text{c}}\) \\ TMT-B & 0.00 \(\pm\) 1.00 & \(-\)0.08 \(\pm\) 0.65 & 2.29 \(\pm\) 2.39 \({}^{\text{b}}\) \\ BVMT-R-Total recall & 0.00 \(\pm\) 1.00 & 0.00 \(\pm\) 1.08 & \(-\)2.21 \(\pm\) 1.98 \({}^{\text{a.c}}\) \\ BVMT-R-Delayed recall & 0.00 \(\pm\) 1.00 & 0.23 \(\pm\) 0.85 & \(-\)2.03 \(\pm\) 2.13 \({}^{\text{a.c}}\) \\ PASAT-3\({}^{\text{a}}\) & 0.00 \(\pm\) 1.00 & \(-\)0.02 \(\pm\) 0.65 & \(-\)2.29 \(\pm\) 1.50 \({}^{\text{a.c}}\) \\ JLOT & 0.00 \(\pm\) 1.00 & 0.31 \(\pm\) 0.781 & \(-\)0.38 \(\pm\) 0.68 \\ \hline \end{tabular} Values are the mean \(\pm\) standard deviation (SD); \({}^{\text{a}}\)\(p\)\(<\) 0.05 compared with HCs; \({}^{\text{b}}\)\(p\)\(<\) 0.05 compared with patients with MS and CP; \({}^{\text{c}}\)\(p\)\(<\) 0.01 compared with patients with MS and CP; Abbreviations: AVLT = Auditory Verbal Learning Test VFT = Verbal Fluency Test; SDMT = Symbol digit modalities test; TMT = Trinal Making Test; BVMT-R = Brief Visuo-Spatial Memory Test-Revised; PASAT-3” = Paced Auditory Serial Addition Test (3 s); JLOT = Judgment of Line Orientation Test; CI = cognitive impairment; CP = cognitive preservation; HC = healthy control.  
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Table 7: Comparison in cognitive tests among the MS patients with CI, MS patients with CP, and HCs.