Cognitive dysfunction is common in multiple sclerosis (MS) and can impair processing speed, episodic memory, and executive function. Magnetic resonance imaging (MRI) studies have demonstrated associations between several MRI metrics and cognitive functioning in MS, including thalamic volume and brain parenchymal fraction. Fingolimod is an MS therapy that demonstrated reduced brain volume loss across several clinical trials.
Determine the relationship between cognitive function in fingolimod-treated relapsing-remitting MS patients and 7 tesla (7T) MRI measures.
We recruited fingolimod-treated MS patients and healthy controls to be followed for 12 months. Participants underwent 7T brain MRI and cognitive testing including the symbol digit modalities test (SDMT), selective reminding test (SRT), and the trail making, color, and verbal subtests of the Delis-Kaplan Executive Function System (DKEFS) at baseline, 6 months, and 12 months. Mixed effects linear regression models were used to determine the relationship between MRI metrics and neurometric test performance, fitting values from all 3 time points. Rates of change in MRI metrics and neurometric test performance were compared between patients and controls using two-sample t-tests.
We enrolled 15 MS patients with mean age 42.4 years (SD=5.6), mean disease duration 8.5 years (SD=4.1), and median expanded disability status scale 3 (IQR=1.5-3.5). Five controls were enrolled with mean age 41.5 (SD=6.6) years. Controls performed better than patients on all psychometric tests, but this was only significant for tests of orthographic knowledge (DKEFS letter fluency) and long-term storage (SRT). When MRI metrics were used to predict neuropsychological test performance over time in patients, thalamic volume was a significant predictor of visuospatial memory (BVMTR), long-term storage (SRT), and inhibitory control (DKEFS Color Inhibition). Thalamic myelin density was a significant predictor of visuospatial memory (BVMTR), long-term storage (SRT), and semantic knowledge (DKEFS Verbal Category Fluency). When changes in neuropsychological testing performance and MRI metrics were compared for patients and controls from 0-6 months, and from 0-12 months, none of the differences between patients and controls were significant.
Thalamic volume and myelin density are associated with measures of cognitive function. 7T MRI of the thalamus may be useful as a clinical trial measure to predict cognitive effects.