Effects of Vascular Disease Risk Factors on Brain ATP in People with Multiple Sclerosis—A 3-year Longitudinal Study
Helen Wu1, Jacob Perlman2, Alexander Stevens1, Michael Lane2, Allison Fryman2, Frank Bittner2, William Rooney1, Manoj Sammi1, Vijayshree Yadav2
1Oregon Health & Science University, 2Dept of Veterans Affairs MSCoE, Oregon Health & Science University
Objective:
Describe the effects of VDRF (vascular disease risk factors) on brain phosphate metabolism and disease progression in pwMS (people with multiple sclerosis) over time.
Background:
VDRF, such as hyperlipidemia, hypertension, obesity, diabetes, and heart disease, appear to significantly increase the risk of disability progression in pwMS, however the underlying mechanisms are not understood. We previously published baseline data that VDRF+ pwMS have significantly reduced brain ATP compared with VDRF- pwMS.
Design/Methods:
This is a 3-year prospective, observational, single-site, study with two arms (pwMS with and without VDRF). We collected 7T MRI and 31P MRS (magnetic resonance spectroscopy) data at baseline (n=51), 12 (n=42), 24 (n=35), 36 (n=33) months, and clinical data every 6 months. Outcome measures include changes in: 1) cerebral ATP, 2) brain parenchymal volume, and 3) clinical outcomes. The ATP data was analyzed using a mixed methods repeated measures model using age, sex, regional brain volume, baseline ATP, and VDRF status for each subject over 4 time points as predictors.
Results:
At baseline, mean age/ sex was 56.4 years/ 82.1% female (N=28) for VDRF+, and 52.4 years/ 56.5% female (N=23) for VDRF-. Preliminary findings suggest that increased age was associated with decreased ATP levels (p<0.01). After controlling for baseline differences, demographic variables, and brain tissue compartments, ATP levels did not change or differ between the two VDRF groups during the 36 month period.
Conclusions:
This is the first longitudinal prospective study to assess brain metabolism in pwMS with and without VDRF. With increasing age, we observed decreased ATP levels. However, the presence of VDRF did not appear to influence ATP levels in this small cohort over the 36 month study period.