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.

• Keywords
• brain atrophy, cholesterol, magnetic resonance imaging,
• MeSH
• Cholesterol blood   MeSH
• Nerve Degeneration blood   diagnostic imaging   drug therapy   pathology   MeSH
• Demyelinating Diseases blood   diagnostic imaging   drug therapy   pathology   MeSH
• Adult MeSH
• Cholesterol, HDL blood   MeSH
• Interferon beta-1a administration & dosage   MeSH
• Cholesterol, LDL blood   MeSH
• Humans MeSH
• Lipids blood   MeSH
• Magnetic Resonance Imaging MeSH
• Brain diagnostic imaging   drug effects   physiopathology   MeSH
• Multiple Sclerosis blood   diagnostic imaging   drug therapy   pathology   MeSH
• Check Tag
• Adult MeSH
• Humans MeSH
• Male MeSH
• Female MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH
• Research Support, N.I.H., Extramural MeSH
• Names of Substances
• Cholesterol MeSH
• Cholesterol, HDL MeSH
• Interferon beta-1a MeSH
• Cholesterol, LDL MeSH
• Lipids MeSH

The purpose of this work was to investigate the associations of serum cholesterol and apolipoproteins with measures of blood-brain barrier (BBB) permeability and CNS inflammation following the first clinical demyelinating event. This study included 154 patients [67% female; age, 29.5 ± 8.2 years (mean ± SD)] enrolled in a multi-center study of interferon β1-a treatment following the first demyelinating event. Blood and cerebrospinal fluid (CSF) were obtained at screening prior to treatment. A comprehensive serum lipid profile and multiple surrogate markers of BBB breakdown and CNS immune activity were obtained. Higher levels of serum HDL cholesterol (HDL-C) and ApoA-I were associated with lower CSF total protein level, CSF albumin level, albumin quotient, and CSF IgG level (all P ≤ 0.001 for HDL-C and all P < 0.01 for ApoA-I). HDL-C was also associated with CSF CD80+ (P < 0.001) and with CSF CD80+CD19+ (P = 0.007) cell frequencies. Higher serum HDL is associated with lower levels of BBB injury and decreased CD80+ and CD80+CD19+ cell extravasation into the CSF. HDL may potentially inhibit the initiation and/or maintenance of pathogenic BBB injury following the first demyelinating event.

• Keywords
• apolipoproteins, cholesterol, clinically isolated syndrome, high density lipoprotein,
• MeSH
• Apolipoproteins blood   cerebrospinal fluid   MeSH
• Biomarkers blood   cerebrospinal fluid   MeSH
• Demyelinating Diseases MeSH
• Adult MeSH
• Cholesterol, HDL blood   MeSH
• Blood-Brain Barrier drug effects   metabolism   pathology   MeSH
• Interferon-beta therapeutic use   MeSH
• Humans MeSH
• Longitudinal Studies MeSH
• Nervous System Diseases blood   cerebrospinal fluid   MeSH
• Multiple Sclerosis blood   cerebrospinal fluid   drug therapy   pathology   MeSH
• Inflammation blood   cerebrospinal fluid   MeSH
• Check Tag
• Adult MeSH
• Humans MeSH
• Male MeSH
• Female MeSH
• Publication type
• Journal Article MeSH
• Multicenter Study MeSH
• Observational Study MeSH
• Research Support, Non-U.S. Gov't MeSH
• Names of Substances
• Apolipoproteins MeSH
• Biomarkers MeSH
• Cholesterol, HDL MeSH
• Interferon-beta MeSH

Cognitive impairment (CI) may occur in clinically isolated syndrome (CIS) patients. While the relationship between CI and magnetic resonance imaging (MRI) has been investigated extensively in multiple sclerosis (MS), MRI correlates of CI in CIS patients are unknown. To investigate the evolution of CI and to determine brain MRI structural correlates associated with CI in CIS patients. This prospective 24-month observational study examined 81 CIS patients treated with 30 µg of intramuscular interferon beta 1a once a week. MRI acquisition and neuropsychological (NP) assessment were performed at baseline, 6, 12 and 24 months. Participants were tested with Czech-validated version of Minimal Assessment of Cognitive Function in MS battery and MRI measures of lesion activity and burden, and global, tissue-specific and regional brain atrophy were performed. Over 24 months, 36 CIS patients developed clinically definite MS (CDMS). CI was observed in 10 (12.3 %) CIS patients at baseline and at the 24 months follow-up. Eight CIS patients changed their CI status over the follow-up (four improved and four worsened). No significant difference in development of CI was detected between stable CIS patients and those who developed CDMS. In multivariate regression and mixed-effect model analyses, no significant relationship was found between NP and MRI parameters. The lack of significant relationship between MRI metrics and cognition in this group of CIS patients could be attributed to several factors including the cognitive reserve, effect of disease-modifying therapy and relatively short follow-up period.

• MeSH
• Demyelinating Diseases drug therapy   immunology   pathology   psychology   MeSH
• Adult MeSH
• Interferon beta-1a MeSH
• Interferon-beta administration & dosage   pharmacology   MeSH
• Cognition drug effects   MeSH
• Cognitive Dysfunction drug therapy   immunology   pathology   MeSH
• Middle Aged MeSH
• Humans MeSH
• Magnetic Resonance Imaging * MeSH
• Adolescent MeSH
• Young Adult MeSH
• Brain pathology   MeSH
• Follow-Up Studies MeSH
• Neuropsychological Tests MeSH
• Disease Progression MeSH
• Prospective Studies MeSH
• Multiple Sclerosis drug therapy   immunology   pathology   psychology   MeSH
• Check Tag
• Adult MeSH
• Middle Aged MeSH
• Humans MeSH
• Adolescent MeSH
• Young Adult MeSH
• Male MeSH
• Female MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH
• Names of Substances
• Interferon beta-1a MeSH
• Interferon-beta MeSH