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

Studies examining the epsilon4 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 epsilon4 allele and other dementia conditions. Only two studies examine the relationship between the epsilon4 allele and cognitive impairment.

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).

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 epsilon2 allele had lower disability and higher scores on the cognitive battery. The epsilon4 allele was not related to physical disability, and there was no difference between epsilon4+ and epsilon4--patients in overall cognitive performance. However, when patients with severe cognitive impairment were identified, a greater proportion (52%) of these patients had the epsilon4 allele than those in the unimpaired group (27%).

An association with the epsilon4 allele was evident in this study, but only in cases of severe cognitive impairment.