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Cognitive impairment in patients with multiple sclerosis: association with the APOE gene and promoter polymorphisms

D R Denney

Department of Psychology, University of Kansas, Lawrence, KS 66045, USA

S G Lynch

Department of Neurology, University of Kansas Medical Center, Kansas City, KS 66160, USA

L S Middleton

Department of Psychology, University of Kansas, Lawrence, KS 66045, USA

L M Harlan

Department of Molecular Biosciences, University of Kansas, Lawrence, KS 66045, USA

Background Studies examining the 4 allele of the APOE gene as a factor affecting the severity of multiple sclerosis (MS) have yielded conflicting results. The focus of these studies on physical disability to the neglect of cognitive impairment is surprising in light of the associations between the 4 allele and other dementia conditions. Only two studies examine the relationship between the 4 allele and cognitive impairment.

Methods A neuropsychological test battery was administered to 263 MS patients, and their current disability status was evaluated. Genotypes were determined for APOE epsilon and for two promoter region polymorphisms (-219 G/T and -491 A/T).

Results Although effects were generally weak, female patients with the -491 AA genotype had a later age of disease onset, lower disability scores, and somewhat higher scores on the cognitive battery. Male patients with the 2 allele had lower disability and higher scores on the cognitive battery. The 4 allele was not related to physical disability, and there was no difference between 4+and 4– patients in overall cognitive performance. However, when patients with severe cognitive impairment were identified, a greater proportion (52%) of these patients had the 4 allele than those in the unimpaired group (27%).

Conclusion An association with the 4 allele was evident in this study, but only in cases of severe cognitive impairment.

Key Words: apolipoprotein gene • cognitive impairment • disability • multiple sclerosis • neuropsychology • promoter

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