APOE ε4 and the cognitive genetics of multiple sclerosis

Background: Evidence linking APOE to myelin repair, neuronal plasticity, and cerebral inflammatory processes suggests that it may be relevant in multiple sclerosis (MS). The purpose of this study was to determine whether the epsilon 4 allele of APOE is associated with cognitive deficits in patients with MS. Method: Using a case-control design, 50 patients with MS with the epsilon 4 allele (epsilon 4+) and 50 epsilon 4-negative (epsilon 4-) patients with MS were tested using a comprehensive battery of tests evaluating the cognitive domains most often affected in MS. Results: The epsilon 4+ and epsilon 4-patients with MS were well-matched with respect to demographic variables (age, gender, ethnicity, education, employment status, premorbid IQ) and disease variables (disease course, disease duration, Expanded Disability Status Scale, 25-foot timed walk, 9-hole pegboard test). In addition, the groups were similar in depressive symptoms, in the proportion of patients receiving disease-modifying therapy, and in carriage of the APOE epsilon 2 allele. Results showed that none of the 11 cognitive outcome variables differed between epsilon 4+ and epsilon 4-patients with MS. Cognitive measures were also unrelated to epsilon 4 interactions with age and gender. The incidence of overall cognitive dysfunction did not differ between epsilon 4+ and epsilon 4- groups, nor did failure on any test, and epsilon 4 carriage was not a significant predictor of any adverse cognitive outcome. These negative results endured with the exclusion of epsilon 2+ subjects from the analyses. Conclusion: This study does not support a role for the epsilon 4 allele in cognitive dysfunction in multiple sclerosis. Neurology (R) 2010; 74: 1611-1618