RT Journal Article SR Electronic T1 Is APOE ε4 associated with cognitive performance in early MS? JF Neurology - Neuroimmunology Neuroinflammation JO Neurol Neuroimmunol Neuroinflamm FD Lippincott Williams & Wilkins SP e728 DO 10.1212/NXI.0000000000000728 VO 7 IS 4 A1 Engel, Sinah A1 Graetz, Christiane A1 Salmen, Anke A1 Muthuraman, Muthuraman A1 Toenges, Gerrit A1 Ambrosius, Björn A1 Bayas, Antonios A1 Berthele, Achim A1 Heesen, Christoph A1 Klotz, Luisa A1 Kümpfel, Tania A1 Linker, Ralf A. A1 Meuth, Sven G. A1 Paul, Friedemann A1 Stangel, Martin A1 Tackenberg, Björn A1 Then Bergh, Florian A1 Tumani, Hayrettin A1 Weber, Frank A1 Wildemann, Brigitte A1 Zettl, Uwe K. A1 Antony, Gisela A1 Bittner, Stefan A1 Groppa, Sergiu A1 Hemmer, Bernhard A1 Wiendl, Heinz A1 Gold, Ralf A1 Zipp, Frauke A1 Lill, Christina M. A1 Luessi, Felix A1 for the German Competence Network of Multiple Sclerosis YR 2020 UL http://nn.neurology.org/content/7/4/e728.abstract AB Objective To assess the impact of APOE polymorphisms 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 (ε4) and rs7412 (ε2) of the APOE haplotype 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 the APOE carrier status on cognitive performance was assessed using multiple linear regression models, also including demographic, clinical, MRI, and lifestyle factors.Results APOE ε4 homozygosity was associated with lower overall cognitive performance, whereas no relevant association was observed for APOE ε4 heterozygosity or APOE ε2 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 for APOE carrier status.Conclusion Along with parameters of a higher disease burden, APOE ε4 homozygosity was identified as a potential predictor of cognitive performance in this large cohort of patients with CIS and early RRMS.AD=Alzheimer disease; BDI-II=Beck Depression Inventory II; BMI=body mass index; CIS=clinically isolated syndrome; EDSS=Expanded Disability Status Scale; FSMC=Fatigue Scale for Motor and Cognitive Function; HWE=Hardy-Weinberg equilibrium; MCI=mild cognitive impairment; MUSIC=Multiple Sclerosis Inventory Cognition; PASAT 3=3-second paced auditory serial addition test; RRMS=relapsing-remitting MS; SNP=single nucleotide polymorphism