PT - JOURNAL ARTICLE AU - Engel, Sinah AU - Graetz, Christiane AU - Salmen, Anke AU - Muthuraman, Muthuraman AU - Toenges, Gerrit AU - Ambrosius, Björn AU - Bayas, Antonios AU - Berthele, Achim AU - Heesen, Christoph AU - Klotz, Luisa AU - Kümpfel, Tania AU - Linker, Ralf A. AU - Meuth, Sven G. AU - Paul, Friedemann AU - Stangel, Martin AU - Tackenberg, Björn AU - Then Bergh, Florian AU - Tumani, Hayrettin AU - Weber, Frank AU - Wildemann, Brigitte AU - Zettl, Uwe K. AU - Antony, Gisela AU - Bittner, Stefan AU - Groppa, Sergiu AU - Hemmer, Bernhard AU - Wiendl, Heinz AU - Gold, Ralf AU - Zipp, Frauke AU - Lill, Christina M. AU - Luessi, Felix AU - for the German Competence Network of Multiple Sclerosis TI - Is <em>APOE</em> ε4 associated with cognitive performance in early MS? AID - 10.1212/NXI.0000000000000728 DP - 2020 Jul 01 TA - Neurology - Neuroimmunology Neuroinflammation PG - e728 VI - 7 IP - 4 4099 - http://nn.neurology.org/content/7/4/e728.short 4100 - http://nn.neurology.org/content/7/4/e728.full SO - Neurol Neuroimmunol Neuroinflamm2020 Jul 01; 7 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