Author Of 2 Presentations
P0606 - MRI changes over the disease course in a large multiple sclerosis clinical cohort (ID 1318)
Abstract
Background
Quantitative MRI measures are proposed as biomarkers of disease course and therapeutic response. Understanding the evolution of these metrics is key for interpretation of change in clinical practice.
Objectives
To describe longitudinal changes in T2 lesion volume (T2LV), whole brain (WBF) and gray matter (GMF) fraction, and thalamic volume (TV) over the disease course in a large multiple sclerosis (MS) cohort.
Methods
Demographics, disease history, and MRI were collected from MS patients at a single site. Patients with ≥2 MRI assessments were included. T2LV, WBF, GMF, and TV annualized rate of change and raw values compared to the first available scan were analyzed. Multivariate mixed-effects models were used to evaluate longitudinal MRI changes, adjusting for age at disease onset, sex, and patient-determined disease steps category (PDDS) with a random intercept for patient and an autoregressive covariance structure. For each outcome, three models were generated: a linear model, a second-order B-spline model, and a third-order B-spline model were tested for nonlinearity in the relationship between MRI outcome and disease duration and were compared based on Akaike Information Criterion.
Results
1012 patients were included (69.2% female, 72.9% relapsing-remitting MS, mean ± SD age at disease onset 34.4±10.3, age at baseline MRI 43.8±11.1, disease duration 9.4±5.8 years, mean number of MRIs 3.1±1.2, median [IQR] PDDS 1.0 [0.0-3.0]). Male sex (B=4.9) and PDDS>3 (B=7.0) were associated with greater T2LV accumulation over the disease course (best fit: linear model). T2LV annualized rate of change peaked at 5-6 years of disease duration (rate 9%/year) (best fit: third-order B spline). Male sex, older age, and PDDS>3 were associated with lower WBF, TV (best fit: linear model), and GMF (best fit: second-order B spline), all p<0.05. No non-linear effect of disease duration on WBF, TV, and GMF were observed. There was no statistically significant change in the annualized rate of change of WBF, TV, and GMF over the disease course.
Conclusions
The dynamics of T2LV accumulation are variable throughout the disease course, whereas the rate of change of WBF, TV, and GMF were more stable. These results suggest T2LV accumulation reflecting focal lesion activity predominates early in the disease while WBF, TV, and GMF loss reflecting underlying neurodegeneration is present at disease onset and continues throughout the course.
P0634 - Relationship Between Cognitive Functioning and 7T Thalamic Imaging Metrics in Fingolimod-Treated MS Patients and Healthy Controls (ID 700)
Abstract
Background
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.
Objectives
Determine the relationship between cognitive function in fingolimod-treated relapsing-remitting MS patients and 7 tesla (7T) MRI measures.
Methods
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.
Results
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.
Conclusions
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.