Gender-related effect of clinical and genetic variables on the cognitive impairment in multiple sclerosis

Background: Cognitive impairment may occur at any time during the course of multiple sclerosis (MS), and it is often a major cause of disability in patients with the disease. The APOE-ε4 allele is the major known genetic risk factor for late onset familial and sporadic Alzheimer's Disease (AD), and it seems to be implicated in cognitive decline in normal elderly persons. Objective: To investigate the clinical and genetic variables that can be associated with the cognitive decline in patients with MS. Methods: Five-hundred and three patients with clinically definite MS underwent a battery of neuropsychological tests and, according to the number of failed tests, were divided into cognitively normal and impaired. All patients were genotyped for APOE gene polymorphisms. Results: Fifty-six percent of MS patients showed, to different extents, cognitive impairment. Cognitive decline was predominant in men and was associated with disease duration, Kurtzke Expanded Disability Status Scale (EDSS) score, a low level of education, and, interestingly, the ε4 allele of the APOE gene. By contrast, cognitive impairment in women was independent of any investigated variable. Conclusion: The findings demonstrate that clinical and genetic factors play a role in men affected by MS developing cognitive impairment.