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.
| Original language | English |
|---|---|
| Pages (from-to) | 403-411 |
| Number of pages | 9 |
| Journal | Journal of Lipid Research |
| Volume | 58 |
| Issue number | 2 |
| DOIs | |
| Publication status | Published - 2017 |
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Keywords
- Brain atrophy
- Cholesterol
- Magnetic resonance imaging
ASJC Scopus subject areas
- Biochemistry
- Endocrinology
- Cell Biology
Cite this
Serum lipid profile changes predict neurodegeneration in interferon-β1a-treated multiple sclerosis patients. / Uher, Tomas; Fellows, Kelly; Horakova, Dana; Zivadinov, Robert; Vaneckova, Manuela; Sobisek, Lukas; Tyblova, Michaela; Seidl, Zdenek; Krasensky, Jan; Bergsland, Niels; Weinstock-Guttman, Bianca; Havrdova, Eva; Ramanathan, Murali.
In: Journal of Lipid Research, Vol. 58, No. 2, 2017, p. 403-411.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Serum lipid profile changes predict neurodegeneration in interferon-β1a-treated multiple sclerosis patients
AU - Uher, Tomas
AU - Fellows, Kelly
AU - Horakova, Dana
AU - Zivadinov, Robert
AU - Vaneckova, Manuela
AU - Sobisek, Lukas
AU - Tyblova, Michaela
AU - Seidl, Zdenek
AU - Krasensky, Jan
AU - Bergsland, Niels
AU - Weinstock-Guttman, Bianca
AU - Havrdova, Eva
AU - Ramanathan, Murali
PY - 2017
Y1 - 2017
N2 - 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.
AB - 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.
KW - Brain atrophy
KW - Cholesterol
KW - Magnetic resonance imaging
UR - http://www.scopus.com/inward/record.url?scp=85011284377&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85011284377&partnerID=8YFLogxK
U2 - 10.1194/jlr.M072751
DO - 10.1194/jlr.M072751
M3 - Article
AN - SCOPUS:85011284377
VL - 58
SP - 403
EP - 411
JO - Journal of Lipid Research
JF - Journal of Lipid Research
SN - 0022-2275
IS - 2
ER -