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Abstract

Objective To assess the impact ofAPOEpolymorphisms on cognitive performance in patients newly diagnosed with clinically isolated syndrome (CIS) or relapsing-remitting MS (RRMS). Methods This multicenter cohort study included 552 untreated patients recently diagnosed with CIS or RRMS according to the 2005 revised McDonald criteria. The single nucleotide polymorphisms rs429358 (epsilon 4) and rs7412 (epsilon 2) of theAPOEhaplotype were assessed by allelic discrimination assays.Cognitive performance was evaluated using the 3-second paced auditory serial addition test and the Multiple Sclerosis Inventory Cognition (MUSIC). Sum scores were calculated to approximate the overall cognitive performance and memory-centered cognitive functions. The impact of theAPOEcarrier status on cognitive performance was assessed using multiple linear regression models, also including demographic, clinical, MRI, and lifestyle factors. Results APOE epsilon 4 homozygosity was associated with lower overall cognitive performance, whereas no relevant association was observed forAPOE epsilon 4 heterozygosity orAPOE epsilon 2 carrier status. Furthermore, higher disability levels, MRI lesion load, and depressive symptoms were associated with lower cognitive performance. Patients consuming alcohol had higher test scores than patients not consuming alcohol. Female sex, lower disability, and alcohol consumption were associated with better performance in the memory-centered subtests of MUSIC, whereas no relevant association was observed forAPOEcarrier status. Conclusion Along with parameters of a higher disease burden,APOE epsilon 4 homozygosity was identified as a potential predictor of cognitive performance in this large cohort of patients with CIS and early RRMS.