Abstract
The purpose of this work was to determine whether changes in cholesterol profiles after interferon-β (IFN-β)1a treatment initiation following the first demyelinating event suggestive of multiple sclerosis are associated with clinical and MRI outcomes over 4 years. A group of 131 patients (age: 27.9 ± 7.8 years, 63% female) with serial 3-monthly clinical and 12-monthly MRI follow-ups over 4 years were investigated. Serum cholesterol profiles, including total cholesterol (TC), HDL cholesterol (HDL-C), and LDL cholesterol (LDL-C) were obtained at baseline, 1 month, 3 months, and every 6 months thereafter. IFN-β1a initiation caused rapid decreases in serum HDL-C, LDL-C, and TC within 1 month of IFN-β1a initiation (all P < 0.001) that returned slowly toward baseline. In predictive mixed model analyses, greater percent decreases in HDL-C after 3 months of IFN-β1a treatment initiation were associated with less brain atrophy over the 4 year time course, as assessed by percent brain volume change (P < 0.001), percent gray matter volume change (P < 0.001), and percent lateral ventricle volume change (P = 0.005). Decreases in cholesterol biomarkers following IFN-β1a treatment are associated with brain atrophy outcomes over 4 years. Pharmacological interventions targeting lipid homeostasis may be clinically beneficial for disrupting neurodegenerative processes.
Highlights
The purpose of this work was to determine whether changes in cholesterol profiles after interferon- (IFN- )1a treatment initiation following the first demyelinating event suggestive of multiple sclerosis are associated with clinical and MRI outcomes over 4 years
We found that each 10 mg/dl of greater baseline LDL cholesterol (LDL-C), total cholesterol (TC), and apoB was associated with a 7.4%, 5.9%, and 16% increase in the number of new T2 lesions over 2 years of IFN- treatment, respectively [22, 23]
Longitudinal associations of cholesterol profile with MRI and clinical measures We investigated the associations of cholesterol profiles at baseline and longitudinal TC%, HDL cholesterol (HDL-C)%, LDL-C% changes occurring after IFN- 1a treatment with the longitudinal clinical and MRI measures
Summary
The purpose of this work was to determine whether changes in cholesterol profiles after interferon- (IFN- )1a treatment initiation following the first demyelinating event suggestive of multiple sclerosis are associated with clinical and MRI outcomes over 4 years. In predictive mixed model analyses, greater percent decreases in HDL-C after 3 months of IFN 1a treatment initiation were associated with less brain atrophy over the 4 year time course, as assessed by percent brain volume change (P < 0.001), percent gray matter volume change (P < 0.001), and percent lateral ventricle volume change (P = 0.005). Decreases in cholesterol biomarkers following IFN- 1a treatment are associated with brain atrophy outcomes over 4 years. Serum lipid profile changes predict neurodegeneration in interferon- 1a-treated multiple sclerosis patients. On MRI, approximately 40% of patients show complete suppression of new contrast-enhancing lesions (CELs), whereas 20% of patients have less than 70% suppression
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