The effect of years of achieved education on the relationship between deep gray matter atrophy and impairment on measures of processing speed in multiple sclerosis

Background. There has been recent interest in the possibility of cognitive reserve in Multiple Sclerosis (MS) patients and cognitive dysfunction. Recent studies have associated higher levels of achieved education with less cognitive dysfunction and brain atrophy. Gray matter atrophy has been posited to be more relevant than white matter or whole brain atrophy and thalamus atrophy has been found to be important predictors of cognitive impairment. We endeavored to assess the role years of achieved education plays in the relationship between cognitive impairment and atrophy of deep gray matter (DGM) structures in MS patients. Methods. This was a retrospective analysis of 143 MS patients with formal neuropsychological testing and a brain MRI within 90 days of each other. Cognitive function was assessed using the Symbol Digit Modalities Test (SDMT), a measure of processing speed. Scores were considered abnormal (cognitive dysfunction) if the z-score was worse than 1.5 standard deviations (SD) below the mean. Deep gray matter structures (caudate, putamen, globus pallidus and thalamus) and total volume were measured using a semiautomated computer program (SIENAX and FIRST) on a 1.5 Tesla MRI. The data was analyzed to determine confounders and logistic regression and stratification were used to determine the significance of education as an effect modifier between DGM volume and cognitive function as determined by the SDMT. Results. Participants were included 114 (79.7%) women with mean (+/- SD) age of 46.1 +/-8.0; 94.4% were Caucasian. The majority of subjects had a relapsing remitting MS course (81.1%), with a median Expanded Disability Status Scale (EDSS) of 2.5; 93 (65.0%) considered mild disability. Age, EDSS (categorical) and sex were found to be possible confounders and thus were included in the analysis. The addition of education as an effect modifier (interaction term) when assessing the relationship between DGM volume and cognitive function (normal vs. affected) and controlling for confounders was not statistically significant for any of the DGM structures or total volume, indicating education was a not an effect modifier but a confounder of this association. There was a consistent pattern for the caudate putamen, thalamus and total volume analyses, all suggesting that larger DGM volumes were associated with protection from being in the abnormal (cognitively impaired) SDMT category. Conclusion. Based on this cross-sectional analysis, education is associated with both cognitive function, as measured by the SDMT, and DGM volume in MS patients, however it does not modify the effect of between these two variables.