Diffusion Tensor Imaging Abnormalities in Cognitively Impaired Multiple Sclerosis Patients

Background: Cognitive impairment can add to the burden of disease in patients with multiple sclerosis (MS). The aim of this study was to assess the relative importance of diffusion tensor imaging (DTI) indices derived from normal appearing white matter (NAWM) and grey matter (NAGM) in determining cognitive dysfunction in MS patients. Methods: Sixty two MS patients [51 female, mean age= 41 (sd=9.6) years, median expanded disability status scale (EDSS)=2.5] meeting modified McDonald criteria for MS underwent neuropsychological testing using the Neuropsychological Screening Battery for MS (NSBMS) and magnetic resonance imaging (MRI, 1.5T GE) that included DTI sequences. Total T(1) hypointense and T(2) hyperintense lesion volumes were obtained using semi-automated software. Lesion volumes were subtracted from whole-brain parenchyma to obtain measures of NAWM and NAGM. Fractional anisotropy (FA) of NAWM and mean diffusivity (MD) of NAGM were obtained. Results: Cognitive impairment was present in 11 patients (18%). These patients had higher EDSS scores, were less educated, and were more likely to have secondary progressive MS. They also had higher hypointense (p=0.001) and hyperintense (p=0.004) lesion volumes, greater NAWM atrophy (p=0.007), lower FA of total NAWM (p=0.003), and higher MD of total NAGM (p=0.015). Using a logistic regression analysis, and after controlling for demographic and disease-related differences between groups, FA of NAWM emerged as a significant predictor of cognitive impairment adding to the variance derived from lesion and atrophy data. Conclusion: This study underlies the important role of normal-appearing brain tissue in the pathogenesis of MS-related cognitive impairment.