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July 2020; 7 (4) ArticleOpen Access

Is APOE ε4 associated with cognitive performance in early MS?

Sinah Engel, Christiane Graetz, Anke Salmen, Muthuraman Muthuraman, Gerrit Toenges, Björn Ambrosius, Antonios Bayas, Achim Berthele, Christoph Heesen, Luisa Klotz, Tania Kümpfel, Ralf A. Linker, Sven G. Meuth, Friedemann Paul, Martin Stangel, Björn Tackenberg, Florian Then Bergh, Hayrettin Tumani, Frank Weber, Brigitte Wildemann, Uwe K. Zettl, Gisela Antony, Stefan Bittner, Sergiu Groppa, Bernhard Hemmer, Heinz Wiendl, Ralf Gold, Frauke Zipp, Christina M. Lill, Felix Luessi, for the German Competence Network of Multiple Sclerosis
First published May 1, 2020, DOI: https://doi.org/10.1212/NXI.0000000000000728
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Abstract

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.

Glossary

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

Footnotes

  • Go to Neurology.org/NN for full disclosures. Funding information is provided at the end of the article.

  • German Competence Network of Multiple Sclerosis coinvestigators are listed in the appendix 2 at the end of the article.

  • The Article Processing Charge was funded by the authors.

  • Received July 14, 2019.
  • Accepted in final form March 27, 2020.

This is an open access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivatives License 4.0 (CC BY-NC-ND), which permits downloading and sharing the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal.

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