Effects of vascular disease risk factors on brain metabolism in multiple sclerosis

Background: Vascular disease risk factors (VDRF) seemingly contribute to disability progression in people with multiple sclerosis (pwMS). One possible mechanism is impaired brain energy metabolism, quantifiable by measuring adenosine triphosphate (ATP) using magnetic resonance spectroscopic imaging (MRSI). Objective: To determine how VDRF affect brain ATP in pwMS. Methods: We performed a 3-year longitudinal prospective study comparing pwMS with and without VDRF (VDRF+ and VDRF-). We collected 7T MRI and MRSI every 12 months, and clinical data every 6 months. The primary outcome was brain ATP. Using a modified Framingham Risk Scale (FRS) and waist circumference (WC) as a measure of abdominal adiposity, we performed a secondary analysis to understand specific vascular disease risk factor contributions. Results: Of the 60 participants recruited, 52 completed sufficient sessions for analysis. VDRF+ had lower ATP at baseline compared to VDRF- (0.296 vs 0.316). This difference was largely unchanged over 3 years. Larger WC associated with lower ATP at baseline (partial r(47)=-0.38). The association between ATP and FRS was weak (partial r(47)=0.10). Discussion: While VDRF associate with impaired brain metabolism in pwMS, appropriate control of risk factors may reduce the risk of worsened metabolic dysfunction over time. Notably, abdominal adiposity negatively affects brain energy metabolism.