Association of Multiple Sclerosis Related Cognitive Impairment with an MRI Derived Composite Score

Abstract

Background: MRI-derived metrics such as atrophy, burden of disease (BOD), and cortical lesions (CL) have independently been reported to be associated with Multiple Sclerosis (MS) related cognitive impairment (CI). Composite scores combining some of these individual metrics have also been shown to improve correlations with MS-related physical disability; however the value of a composite score for MS-related CI has not yet been evaluated. In this study we assessed the relationship between CI and a quantitative composite score constructed from MRIderived metrics to include total white matter lesion volume, CL number, and normalized cerebrospinal fluid (nCSF), a measure of brain atrophy. Methods: Thirty three (n=33) patients underwent neuropsychological testing and were classified into CI groups using a 4-point severity scale (0, 1, 2, 3) where zero indicates non-impaired, “1” represents borderline, “2” represents mild, and “3” represents moderate CI. Images obtained at 3T were segmented into tissue and lesion compartments from which BOD and nCSF were quantitatively measured. CL number was identified visually by consensus. BOD, nCSF, and CL number were then transformed to z-scores: zBOD, znCSF and zCL, and a composite score “Z3”was constructed from these measures. The associations between Z3 and CI and the individual transformed measures (z-scores) and CI were evaluated via ordinal logistic regression. Results: Z3 was significantly associated with CI (OR=1.443, 95% Confidence Interval: 1.048-1.987, p=0.024) with a slightly larger OR than any individual measure. Of the individual measures, only BOD had a significant association with CI (OR=1.064, 95% Confidence Interval: 1.008-1.123, p=0.025). No significant association was found between atrophy or CL and CI. Conclusion: The Z3 score is associated with increased CI severity. This association was mainly driven by BOD. Larger studies are needed to assess the potential advantage of a composite score over measures of white matter lesion burden alone.