title: Apolipoprotein E ε4-positive multiple sclerosis patients develop more gray-matter and whole-brain atrophy: a 15-year disease history model based on a 4-year longitudinal study.
abstract: Multiple sclerosis is a disease with considerable individual variation, and genetic background plays a key role in disease susceptibility and severity. The objective of the study was to evaluate the relationship between apolipoprotein E (APOE) genotype and the evolution of different clinical and MRI parameters. We investigated a group of 150 relapsingremitting patients that completed 4-year follow-up. The mean age was 30.2 years, disease duration 56.8 months, and baseline Expanded Disability Status Scale (EDSS) 1.8. The changes in brain parenchymal volume (BPV), gray matter (GMV), white matter (WMV) and peripheral gray volume (PGMV) were measured by SIENA/X. T2-lesion volume was assessed by semi-automated methods. The mixed-effect model analysis was used to investigate evolution of clinical and MRI parameters in relation to the APOE ε4 genotype considering two different time models: 4-year follow-up and 15-year period from disease onset. We identified 36 APOE ε4-positive patients. Decline of GMV (P = 0.017), and BPV (P = 0.029) were significantly faster in APOE ε4-positive than in APOE ε4-negative patients in the 15-year model. In the 4- year model, a trend for faster decrease of GMV was found in APOE ε4-positive patients (P = 0.067). No differences in other MRI parameters or EDSS were found between the APOE groups. The results of the study suggest that APOE ε4-positive patients experience faster rate of gray matter atrophy.
authors.affiliation: Charles University in Prague, First Faculty of Medicine, Department of Neurology and Center of Clinical Neuroscience, Prague, Czech Republic. dana.horak@post.cz
authors.forename: D
authors.initials: D
authors.lastname: Horáková
authors.forename: M
authors.initials: M
authors.lastname: Kýr
authors.forename: E
authors.initials: E
authors.lastname: Havrdová
authors.forename: O
authors.initials: O
authors.lastname: Doležal
authors.forename: P
authors.initials: P
authors.lastname: Lelková
authors.forename: L
authors.initials: L
authors.lastname: Pospíšilová
authors.forename: N
authors.initials: N
authors.lastname: Bergsland
authors.forename: M G
authors.initials: MG
authors.lastname: Dwyer
authors.forename: J L
authors.initials: JL
authors.lastname: Cox
authors.forename: S
authors.initials: S
authors.lastname: Hussein
authors.forename: Z
authors.initials: Z
authors.lastname: Seidl
authors.forename: M
authors.initials: M
authors.lastname: Vaněčková
authors.forename: J
authors.initials: J
authors.lastname: Krásenský
authors.forename: R
authors.initials: R
authors.lastname: Zivadinov
mesh_terms: D000276:Adjuvants, Immunologic / Q000627:therapeutic use; D000328:Adult; D000893:Anti-Inflammatory Agents / Q000627:therapeutic use; D053327:Apolipoprotein E4 / Q000235:genetics* / Q000276:immunology; D001284:Atrophy / Q000473:pathology; D001379:Azathioprine / Q000627:therapeutic use; D001921:Brain / Q000473:pathology*; D018450:Disease Progression; D004359:Drug Therapy, Combination; D005260:Female; D005500:Follow-Up Studies; D005838:Genotype; D006801:Humans; D007091:Image Processing, Computer-Assisted; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D000068556:Interferon beta-1a; D016899:Interferon-beta / Q000627:therapeutic use; D008137:Longitudinal Studies; D008279:Magnetic Resonance Imaging; D008297:Male; D020529:Multiple Sclerosis, Relapsing-Remitting / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology; D009413:Nerve Fibers, Myelinated / Q000473:pathology; D011241:Prednisone / Q000627:therapeutic use
chemical_list: D000276:Adjuvants, Immunologic; D000893:Anti-Inflammatory Agents; D053327:Apolipoprotein E4; D007166:Immunosuppressive Agents; D016899:Interferon-beta; D001379:Azathioprine; D011241:Prednisone; D000068556:Interferon beta-1a