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