To determine correlations between cognitive function in fingolimod treated multiple sclerosis (MS) patients and 7 tesla (7T) magnetic resonance imaging (MRI) measures.

Cognitive dysfunction is common in MS and can impair processing speed, episodic memory, and executive function. 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 has a protective effect on brain volume. We elected to study the relationship between 7T MRI metrics and cognitive functioning in MS patients taking fingolimod.

We recruited MS patients to undergo 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). Cortical thickness, brain parenchymal fraction, thalamic volume (TV), and thalamic axon and myelin densities were derived. Spearman correlations were calculated between neuropsychological tests and MRI metrics, and a bootstrap bias-corrected and accelerated method was used to calculate 95% confidence intervals (CI).

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). TV was significantly correlated with DKEFS trail making performance (ρ=0.54, 95%CI=0.03-0.84) and long term storage on the SRT (ρ=0.61, 95%CI=0.02-0.87). Thalamic axon density was significantly correlated with DKEFS verbal performance (ρ=0.44, 95%CI=0.01-0.73) but thalamic myelin density was not significantly correlated with cognitive performance. Moderate correlations that did not reach significance included TV with consistent long term retrieval on the SRT (ρ=0.55, 95%CI=-0.03-0.83) and cortical thickness with recall at 30 minutes on the SRT (ρ=0.47, 95%CI=-0.04-0.77). The SDMT did not strongly correlate with any MRI metrics.

Thalamic volume and axonal density significantly correlated with measures of cognitive flexibility, verbal learning, and retrieval.