ApoE epsilon 4 positive multiple sclerosis patients develop more gray matter and whole brain atrophy: a 4-year longitudinal study using the 15-year disease onset model

• Published in: Multiple sclerosis 2008-09, Vol.14, p.S68-S68
• Main Authors: Horakova, D, Kyr, M, Havrdova, E, Dolezal, O, Seidl, Z, Vaneckova, M, Pospisilova, L, Dwyer, M G, Stosic, M, Cox, J L, Bergsland, N, Zivadinov, R
• Format: Article
• Language: English
• ISSN: 1352-4585

Background: Multiple sclerosis (MS) is a disease with considerable individual variation, and genetic background plays a key role in disease susceptibility and severity. Objective: To evaluate the relationship between ApoE genotype and the evolution of different MRI parameters in relapsing-rernitting MS over 4 years. Methods: We investigated a group of 150 patients from the original ASA (Avonex-Steroid-Azathioprine) study that completed 4-year follow-up. The mean age was 30 years, disease duration 44 months (minimum 0.7; maximum 179 months), Expanded Disability Status Scale (EDSS) was 2.0 and an annualized relapse rate before study was 2. Measures of brain parenchymal volume (BPV), gray matter volume (GMV), white matter volume (WMV) and peripheral gray volume (PGV) were obtained by SIENAX. In addition, T2-lesion and lateral ventricle volumes were assessed with the semiautomated methods. Using a mixed effect model, a 15-year evolution of MRI parameters with respect to the disease onset was built. Different demographic parameters (age, gender, disease duration) were used as covariates to assess inter-individual variation. Results: We identified 36 ApoE epsilon 4 positive and 114 ApoE epsilon 4 negative patients. Over the 4-year interval, a borderline trend for higher decrease of GMV was found in ApoE epsilon 4 pos patients (p=0.074). In the 15-year disease onset model, the higher decline in GMV evolution became highly significant in ApoE epsilon 4 positive patients (p=0.009). Moreover, there was significant difference in the higher decrease of PGV (p=0.003) and BPV (p=0.029) in ApoE epsilon 4 pos patients. No differences were found for the lesion measures. Conclusions: Our results showed higher development of brain (in particular, GM) atrophy in ApoE epsilon 4 pos MS patients over 4 years and in the 15-year disease onset model.