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Clinical Trial
. 2025 Dec:104:106700.
doi: 10.1016/j.msard.2025.106700. Epub 2025 Sep 10.

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

Jacob Perlman  1 , Helen Wu  2 , Allison Fryman  1 , Michael Lane  1 , Frank Bittner  3 , Manoj K Sammi  4 , William D Rooney  4 , Alexander Stevens  4 , Vijayshree Yadav  5
Affiliations
Clinical Trial

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

Jacob Perlman et al. Mult Scler Relat Disord. 2025 Dec.

Abstract

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.

Clinical trial number: NCT02424825.

Keywords: Brain Metabolism; MR Spectroscopy; Vascular disease; adenosine triphosphate(ATP); obesity.

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Conflict of interest statement

Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

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