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.
- Copyright © 2020 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology.
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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