Vascular Disease Risk Factors in Multiple Sclerosis (MS) is Associated with Brain Adenosine Triphosphate Abnormalities: Dysmetabolism May Drive MS Disease Progression
Vijayshree Yadav1, Michael Lane1, Allison Fryman1, Manoj Sammi2
1Oregon Health Science University and Department of Veterans Affairs MS Center of Excellence, 2Oregon Health Science University
Objective:

Determine if the presence of VDRF affects the disease progression and brain phosphate metabolism in people with MS.

Background:
VDRF, such as hyperlipidemia, hypertension, obesity, diabetes, and heart disease, appear to significantly increase the risk of disability progression in MS, however the underlying mechanisms are not well understood. 
Design/Methods:
This is a 3-year prospective, observational, single-site, study with two arms (MS subjects with and without VDRF). We collect 7T MRI brain data at baseline, 12, 24 and 36 months (V1, V2, V3 and V4 visits, respectively) and clinical and biomarkers data every 6 months. Outcome measures include changes in: 1) high energy phosphate metabolites in cerebral gray matter assessed by 31P 7T MR imaging (MRSI) and 2) brain parenchymal volume, 3) clinical impairment, disability, and quality of life.
Results:
We preformed cross-sectional and longitudinal analyses of MRI data (52 V1 and 37 V3 subjects). Mean age/gender was 54.6 years with 71% female) (+VDRF, N=29, mean age 56.3 years, 83% female) and -VDRF, N=23, mean age 52.4 years; 57% female) at baseline. We analyzed a volume of interest in the occipital region for changes in phosphate metabolites (V1 and V3) using 7T MRSI. We observed decrease in Adenosine triphosphate (ATP) to total phosphate signal ratio in +VDRF subjects by 3.3% (P<0.05) compared with -VDRF. +VDRF subjects showed a larger reduction in parenchymal volume fraction (0.01544, P=0.025) over time (between V1 and V3) compared to ‑VDRF (0.00423). No significant group differences in temporal changes in phosphate metabolites are seen. Additional analyses are underway.
Conclusions:
This is the first study to assess brain metabolism and volume in MS patients with and without VDRF. +VDRF MS subjects have significantly reduced brain ATP compared with -VDRF. ATP depletion may reflect mitochondrial dysfunction and contribute to MS disease progression as suggested by the increased brain atrophy in those with VDRF.