Digit Span Tests Are More Sensitive Than SDMT for Detecting Working Memory Impairment and Correlate with Metabolic Alterations in White Matter and Deep Gray Matter Nuclei in Multiple Sclerosis: a GABA-edited Magnetic Resonance Spectroscopy Study

Background: Single Digit Modality Test (SDMT) has been claimed to be one of the most sensitive tests to measure attention and information processing speed in multiple sclerosis (MS). Objectives: We aimed to evaluate the efficacy and usefulness of three brief, easy-to-administer, and repeatable tests: SDMT, Digit Span Forward (DSF), and Digit Span Backward (DSB) in MS patients (MSp), and compare the results with those of healthy volunteers (CON). We were hoping to identify the most sensitive test that would be used in clinical practice on a regular basis. In addition, we tried to identify the metabolic background of the cognitive setting using the advanced radiological method, Mescher-Garwood (MEGA)-edited 1H - Magnetic Resonance Spectroscopy (1H - MRS). Methods: 22 relapsing MSp and 23 age-, education-, and gender-matched CON were enrolled. In MSp, clinical disability was evaluated using Expanded Disability Status Scale (EDSS). The SDMT, DSF, and DSB tests were used in all participants. They also underwent a 1H - MRS brain examination. In addition to N-Acetyl-Aspartate (tNAA), Myoinositol (mIns), and Choline (tCho), and Creatine (tCr) containing compounds were also evaluated GABA and Glutamate-Glutamine (Glx) ratios. Results: CON were superior to MSp in results of all neurocognitive tests. The DSB was found to be the most sensitive test to identify MSp. The SDMT in MSp correlated with inflammatory and degenerative metabolites in the thalamus, hippocampus, and corpus callosum. A correlation between increased Glx- and GABA-ratios and SDMT was found. Unlike the SDMT, the DSF and DSB showed correlations with inflammatory metabolites in the caudate nucleus and hypothalamus. DSF correlated with GABA-ratios in hippocampus. Conclusion: Our study confirms efficacy of DSF and DSB tests in evaluating working memory cognitive impairment in MSp, showing an association of the tests with specific brain metabolites.